c-peptide and Diabetes-Mellitus

Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.

Topics: Animals; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Quality of Life

Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications.. Publications reporting data for glucose, HbA. BIVAC assessment of 47 publications delivered 1 A, 3 B, 39C and 4 D gradings. Publications relating to adiponectin, C-peptide, IGF-1, IGFBP-3, lactate and pyruvate were all assessed as grade C. Meta-analysis enabled global BV estimates for all analytes except pyruvate, lactate and fructosamine.. This study delivers updated and evidence-based BV estimates for diabetes-related analytes. There remains a need for delivery of new high-quality BV studies for several clinically important analytes.

Topics: Adiponectin; Blood Glucose; C-Peptide; Diabetes Mellitus; Fructosamine; Glycated Hemoglobin; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lactic Acid; Pyruvic Acid

The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed information and blood samples have been collected from more than 8000 children and adolescents with newly diagnosed diabetes. We have been able to demonstrate that by means of HLA diabetes antibodies and C-peptide the discrimination between type one and type 2 diabetes is improved. These analyses are therefore included in the clinical check-up for all children and adolescents in Sweden who are diagnosed with diabetes. Type 1 diabetes is by far the most prevalent type of diabetes among Swedish children and adolescents. Type 2 diabetes is still relatively rare in Sweden but it is urgent to obtain a correct diagnosis as the long-term prognosis depends on a prompt pharmacological treatment. Monogenic diabetes (MODY) is also important to identify early. We therefore recommend that sequencing of MODY genes should be performed if an individual with newly-diagnosed diabetes is auto-antibody negative and has an HLA pattern associated with low risk for type 1 diabetes. However, despite these analytical tools it can be difficult to make the correct diabetes diagnosis initially. It is therefore prudent to re-evaluate the diabetes diagnosis after one year.

Topics: Adolescent; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnostic Tests, Routine; Histocompatibility Testing; Humans; Infant; Sweden

β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplantation Association held a workshop to develop consensus for an International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplant Association Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c) and the occurrence of severe hypoglycemia. Optimal β-cell graft function is defined by near-normal glycemic control (HbA1c ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good β-cell graft function requires HbA1c less than 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal β-cell graft function is defined by failure to achieve HbA1c less than 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good function are considered successful clinical outcomes.

Topics: Biomarkers; Blood Glucose; C-Peptide; Consensus; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Risk Factors; Treatment Outcome

C-peptide secretion is deficient or absent in type 1 diabetes mellitus. It is well accepted that insulin replacement therapy cannot prevent the development of long-term diabetes-related complications, which can often be disabling or even life-threatening. Several cross-sectional investigations have suggested that residual C-peptide production in patients with type 1 diabetes mellitus would help prevent a number of complications. In animal models of diabetes and in patients with type 1 diabetes mellitus, C-peptide replacement improves renal function, skin and skeletal muscle blood flow, nerve conduction, glucose utilization, and other diabetes-related complications. Recent investigations suggest a new beneficial effect of C-peptide, which to date has never been studied. It is known that osteoporosis is the most prevalent short-term complication in type 1 diabetes mellitus. This review will highlight new insights into the pathophysiology and future therapeutic modalities for osteoporosis in individuals with diabetes.. This review provides a concise summary of old and new insights into the role of C-peptide in diabetes-related complications.. Taken together these studies encourage further investigations to elucidate the role of C-peptide in preventing bone loss in type 1 diabetes mellitus and in those individuals with C-peptide deficiency and osteoporosis.

Topics: Bone and Bones; C-Peptide; Diabetes Complications; Diabetes Mellitus; Fractures, Bone; Humans; Osteoporosis

G protein-coupled receptors (GPCRs) are the most abundant receptor family encoded by the human genome and are the targets of a high percentage of drugs currently in use or in clinical trials for the treatment of diseases such as diabetes and its associated complications. Thus, orphan GPCRs, for which the ligand is unknown, represent an important untapped source of therapeutic potential for the treatment of many diseases. We have identified the previously orphan GPCR, GPR146, as the putative receptor of proinsulin C-peptide, which may prove to be an effective treatment for diabetes-associated complications. For example, we have found a potential role of C-peptide and GPR146 in regulating the function of the retinal pigment epithelium, a monolayer of cells in the retina that serves as part of the blood-retinal barrier and is disrupted in diabetic macular oedema. However, C-peptide signalling in this cell type appears to depend at least in part on extracellular glucose concentration and its interaction with insulin. In this review, we discuss the therapeutic potential of orphan GPCRs with a special focus on C-peptide and GPR146, including past and current strategies used to 'deorphanize' this diverse family of receptors, past successes and the inherent difficulties of this process.

Topics: Animals; C-Peptide; Cell Differentiation; Diabetes Complications; Diabetes Mellitus; Glucose; Humans; Hypoglycemic Agents; Insulin; Receptors, G-Protein-Coupled; Retinal Pigment Epithelium; Signal Transduction

Diabetes is not a single homogeneous disease but composed of many diseases with hyperglycaemia as a common feature. Four factors have, historically, been used to identify this diversity: the age at onset; the severity of the disease, i.e. degree of loss of beta cell function; the degree of insulin resistance and the presence of diabetes-associated autoantibodies. Our broad understanding of the distinction between the two major types, type 1 diabetes mellitus and type 2 diabetes mellitus, are based on these factors, but it has become apparent that they do not precisely capture the different disease forms. Indeed, both major types of diabetes have common features, encapsulated by adult-onset autoimmune diabetes and maturity-onset diabetes of the young. As a result, there has been a repositioning of our understanding of diabetes. In this review, drawing on recent literature, we discuss the evidence that autoimmune type 1 diabetes has a broad clinical phenotype with diverse therapeutic options, while the term non-autoimmune type 2 diabetes obscures the optimal management strategy because it encompasses substantial heterogeneity. Underlying these developments is a general progression towards precision medicine with the need for precise patient characterisation, currently based on clinical phenotypes but in future augmented by laboratory-based tests.

Topics: Age Factors; Alleles; Autoantibodies; Autoimmunity; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Genotype; Humans; Hyperglycemia; Insulin; Insulin Resistance; Phenotype

Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes.

Topics: Animals; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Hypoglycemic Agents; Receptor, Insulin

Many biological roles have been assigned to proinsulin C-peptide over the years. Some appear surprisingly disparate and sometimes even contradictory, like chaperone-like actions and depository tendencies. This review summarizes recently reported biomolecular interactions of the peptide and presents how they correlate with structural and functional aspects into a partitioned molecular architecture. At the structural level, the C-peptide sequence and fold can be subdivided into three distinct parts ('tripartite'). At the functional level, its chaperone-like abilities, self-assembly, and membrane interactions, as well as interactions with relevant proteins can be separately ascribed to these three segments. At the biological level, the assignments are compatible with the suggested roles of C-peptide in granular insulin storage, chaperone-like activities on insulin oligomers, possible depository tendencies, and proposed receptor interactions. Finally, the assignments give interesting parallels to further bioactive peptides, including glucagon and neurotensin. Provided pharmaceutical and clinical trials are successfully completed, the present interpretations should supply mechanistic explanations on C-peptide as a bioactive compound of importance in health and diabetes.

Topics: Amino Acid Sequence; Animals; Binding Sites; C-Peptide; Conserved Sequence; Diabetes Mellitus; Humans; Insulin; Molecular Sequence Data; Proinsulin; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, G-Protein-Coupled

C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3-5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin Secretion; Prognosis

C-peptide is known for several decades. It is released in equimolar amounts together with insulin from the pancreatic beta cells. Still there has been quite remarkable lack of interest in C-peptide. C-peptide is rarely used to classify type of diabetes although it seems self-evident that it is important to estimate the function of those cells which do not function good enough and therefore causes a syndrome which requires life-long treatment and leads to serious complications. Not until recent years C-peptide is accepted as a relevant outcome in trials aiming at preservation of beta cell function, although it is known for decades that some C-peptide is associated with less complications in type 1 diabetes (T1D). Preservation of beta cell function is important to make diabetes milder, and when beta cell function can be preserved before clinical manifestation of T1D, we are on our way to prevent that disease. Residual C-peptide/insulin secretion can be of value in classification of diabetes in different types. C-peptide may give valuable clinical information on why patients are more or less stable/labile in their blood glucose and more or less easy to treat. It explains why patients with T1D have different tendency to develop severe acute complications, both severe hypoglycaemia and diabetic keto-acidosis (DKA). Longstanding C-peptide may decrease risk of developing severe late complications. Finally, although still under debate, C-peptide seems to have several effects on different organs suggesting that it is an important hormone, interesting per se, and not only as a reflection of insulin secretion.

Topics: Biomarkers; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells

Postmortem chemistry is becoming increasingly essential in the forensic pathology routine and considerable progress has been made over the past years. Biochemical analyses of vitreous humor, cerebrospinal fluid, blood and urine may provide significant information in determining the cause of death or in elucidating forensic cases. Postmortem chemistry may essentially contribute in the determination of the cause of death when the pathophysiological changes involved in the death process cannot be detected by morphological methods (e.g. diabetes mellitus, alcoholic ketoacidosis and electrolytic disorders). It can also provide significant information and useful support in other forensic situations, including anaphylaxis, hypothermia, sepsis and hormonal disturbances. In this article, we present a review of the literature that covers this vast topic and we report the results of our observations. We have focused our attention on glucose metabolism, renal function and electrolytic disorders.

Topics: Biomarkers; Bodily Secretions; Body Fluids; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Electrolytes; Forensic Pathology; Fructosamine; Glucose; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Ketone Bodies; Kidney Function Tests; Postmortem Changes

Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients.

Topics: Animals; Atherosclerosis; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Inflammation; Insulin; Insulin Resistance; Models, Biological; Proinsulin; Signal Transduction

The right classification for diabetes mellitus (DM) allows a more adequate treatment and comprises four categories: type 1 DM, type 2 DM, other types, and gestational diabetes. In some cases, there might be a superposition of situations, especially with regard to the DM that initiates in the young adult or is initially presented with diabetic ketoacidosis intermediately to type 1 and 2 DM. Thus, additions to the classic classification system have been proposed as assessing the presence of autoimmunity (antibody) and b cell function (C-peptide) to precisely define the subtypes. The aim of this literature review was to analyze these diagnostic indexes` performance in the DM classification and to describe subtypes with details. The antibodies against pancreas confirm autoimmunity, and the antibody against insulin is more accurate before 5 years old, while the anti-glutamic acid decarboxylase is more accurate after 20 years old, a test which remains positive for a longer period. The measurement of C-peptide evaluates the pancreatic insulin reserve, and the most largely used methods of stimulation are the measurement after meals or after intravenous glucagon. C-peptide values < 1.5 ng/ml define a patient with absent pancreatic function and, above this value, patients with preserved function. When the presence of antibodies (A+) directed to the pancreas is combined to its insulin secretion capability (β+), it is possible to subdivide DM`s classification in type 1A (A+β-) and 1B (A+β-); and type 2A (A+β+) and 2B (A-β+), which allows a more precise classification and treatment besides opening horizons for the understanding of DM pathogenesis.

Topics: Autoantibodies; Autoimmunity; C-Peptide; Diabetes Mellitus; Glutamate Decarboxylase; Humans

Exogenous C-peptide administration has beneficial effects in many of the tissues commonly affected by diabetic complications. Diabetes-induced circulatory impairments such as decreased blood flow are prevented by C-peptide, possibly via Ca2+-mediated effects on nitric oxide release. C-peptide also improves diabetes-induced erythrocyte deformability, which likely improves oxygen availability and uptake in affected tissues. Furthermore, C-peptide prevents diabetic neuropathy via improvements of endoneural blood flow and by preventing axonal swelling. In the kidney, C-peptide normalizes the diabetes-induced increase in oxygen consumption via inhibition of the Na+/K+-ATPase. Surprisingly, C-peptide has also been shown to prevent complications in patients with type II diabetes. Taken together, these results may indicate that C-peptide treatment has the potential to reduce the prevalence of diabetic complications. In this paper, the current knowledge regarding these beneficial effects of C-peptide administered to diabetic subjects will be reviewed briefly.

Topics: Animals; C-Peptide; Diabetes Mellitus; Humans; Insulin; Neuroprotective Agents; Nitric Oxide; Oxygen

Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its bearings on understanding protein biosynthesis; the pioneering role of insulin, proinsulin, C-peptide, and mini-C-peptides in the development of recombinant DNA technology; and the discovery of the enzymes for the endoproteolytic processing of proinsulin into insulin and C-peptide, completing the pathway of biosynthesis. Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions.

Topics: Animals; Biomarkers; Biomedical Research; C-Peptide; Diabetes Mellitus; History, 20th Century; Humans; Insulin; Reagent Kits, Diagnostic; Recombinant Proteins

The proinsulin connecting peptide, C-peptide, is a cleavage product of insulin synthesis that is co-secreted with insulin by pancreatic beta-cells following glucose stimulation. Recombinant insulin, used in the treatment of diabetes, lacks C-peptide and preclinical and clinical studies suggest that lack of C-peptide may exacerbate diabetes-associated complications. In accordance with this, several studies suggest that C-peptide has beneficial effects in a number of diabetes-associated complications. C-peptide has been shown to prevent diabetic neuropathy by improving endoneural blood flow, preventing neuronal apoptosis and by preventing axonal swelling. In the vascular system, C-peptide has been shown to prevent vascular dysfunction in diabetic rats, and to possess anti-proliferative effects on vascular smooth muscle cells, which may prevent atherosclerosis. However, C-peptide depositions have been found in arteriosclerotic lesions of patients with hyperinsulinemic diabetes and C-peptide has been shown to induce pro-inflammatory mediators, such as nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2, indicating that C-peptide treatment could be associated with side-effects that may accelerate the development of diabetes-associated complications. This review provides a brief summary of recent research in the field and discusses potential beneficial and detrimental effects of C-peptide supplementation.

Topics: Animals; Apoptosis; Blood Vessels; C-Peptide; Cardiovascular Diseases; Cell Proliferation; Diabetes Complications; Diabetes Mellitus; Humans; Immune System; Neovascularization, Physiologic; Neurons; Risk Assessment; Treatment Outcome

To evaluate the lipoprotein profiles, triglycerides and glycemia along with the abdominal fat to explore the risk factors associated with non-diabetic state to IGF, IGT and Type-2 diabetes in Canadian population.. We examined 780 subjects using the ADA and WHO criteria to classify them into groups based on (1) normal glucose tolerance with FBS <6.0 and 2hBS <7.0 mmol/l), (2) IFG; FPG > or =6.1 mmol/l but 2hBS >7.8-11.1 mmol/l; (3) combined IFG/IGT (FPG > or =7.0 mmol/l and 2hBS >11.1 mmol/l). We compared the three groups for glycemia, insulin secretion and insulin sensitivity based on their WHR, abdominal and visceral fat measurements.. The subjects with higher 2 hrs glucose levels 5.2 for NGT vs. 9.1 for IGT and 13.4 mmol/l for NIDDM, p<0.001, apo C-III level (12.8 (DM) vs. 8.9 mg/dl (normal), p<0.001), waist to hip ratio (0.91 (IGT) vs. 0.89 (Normal), p<0.01) and abdominal fat and were found to be highly insulin resistant.. The higher apolipoproteins levels, BMI and abdominal and visceral fat accompanied by poor glycemia were shown to be associated strongly with the metabolic abnormalities. These factors led to the worsening of insulin secretory dysfunction and insulin resistance and were strong predictors of diabetes.

Topics: Adipose Tissue; Atherosclerosis; Biomarkers; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetic Angiopathies; Fatty Acids, Nonesterified; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Metabolic Syndrome; Risk Factors; Triglycerides

Islet cell transplantation recently has emerged as one the most promising therapeutic approaches to improving glycometabolic control in type 1 diabetic patients, and, in many cases, to obtaining insulin independence. Islet cell transplantation requires a relatively short hospital stay and has the advantage of being a relatively noninvasive procedure. The rate of insulin independence 1 year after islet cell transplantation has improved significantly in recent years (60% at 1 year after transplantation compared to the 15% in the past years). Data from a recent international trial confirmed that islet cell transplantation potentially can be a cure for type 1 diabetes. Recent data indicate that insulin independence after islet cell transplantation is associated with an improvement in glucose metabolism and quality of life and with a reduction in hypoglycemic episodes. Islet cell transplantation is still in its initial stages, and many obstacles still need to be overcome. Once clinical islet transplantation has been established, this treatment could be offered to diabetic patients long before the onset of diabetic complications or to patients with life-threatening hypoglycemic unawareness and brittle diabetes.

Topics: C-Peptide; Diabetes Mellitus; Humans; Islets of Langerhans Transplantation

Topics: Aldehyde Reductase; Animals; Antioxidants; C-Peptide; Diabetes Mellitus; Diabetic Neuropathies; Disease Progression; Drug Design; Endothelium, Vascular; Humans; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Peripheral Nerves; Protein Kinase C; Protein Kinase C beta; Thioctic Acid; Vasodilation

Diabetes is an increasingly common disorder which causes and contributes to a variety of central nervous system (CNS) complications which are often associated with cognitive deficits. There appear to be two types of diabetic encephalopathy. Primary diabetic encephalopathy is caused by hyperglycemia and impaired insulin action, which evolves in a diabetes duration-related fashion and is associated with apoptotic neuronal loss and cognitive decline. This appears to be particularly associated with insulin-deficient diabetes. Secondary diabetic encephalopathy appears to arise from hypoxic-ischemic insults due to underlying microvascular disease or as a consequence of hypoglycemia. This type of cerebral diabetic complication is more common in the type 2 diabetic population. Here, we will review the clinical and experimental data supporting this conceptual division of diabetic CNS complications and discuss the underlying metabolic, molecular, and functional aberrations.

Topics: Animals; Apoptosis; C-Peptide; Central Nervous System Diseases; Cognition; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Insulin

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that--nearly 40 years after its discovery--may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications.

Topics: Animals; C-Peptide; Cardiovascular Diseases; Cardiovascular System; Cell Membrane; Diabetes Mellitus; Humans; Nervous System; Nervous System Diseases; Signal Transduction

During the past decade, numerous studies in both humans and animals have demonstrated that C-peptide, although not influencing blood sugar control, might play a role in preventing and potentially reversing some of the chronic complications of type 1 diabetes. The aim of this paper is to present an up-to-date review of C-peptide, focusing on its role in insulin biosynthesis and in the classification of diabetes mellitus, as well as its potential clinical applications.. The relevant literature cited in the MEDLINE database shows that the measurement of C-peptide production combined with screening for the presence of islet-cell and other autoantibodies seems to exert an important role in the accurate differentiation between patients with type 1 and type 2 diabetes. Also, both experimental and clinical data provide evidence suggesting that combined replacement of insulin and C-peptide has potential therapeutic value in patients with type 1 diabetes.. Further study in this area is warranted, but the findings that pancreas transplants promote the reversal of diabetic neuropathy and stabilization of diabetic retinopathy and that both pancreas and islet transplants lead to the reversal of diabetic nephropathy lend credence to the concept that combined replacement of insulin and C-peptide may more effectively mitigate the inexorable progression of diabetes-related complications.

Topics: Adolescent; Adult; Animals; Artifacts; C-Peptide; Calcium Signaling; Child; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Insulin; Kidney; Liver; Mammals; Middle Aged; Pancreas Transplantation; Proinsulin; Protein Precursors; Protein Processing, Post-Translational

The proinsulin C-peptide has been held to be merely a by-product in insulin biosynthesis, but recent reports show that it elicits both molecular and physiological effects, suggesting that it is a hormonally active peptide. Specific binding of C-peptide to the plasma membranes of intact cells and to detergent-solubilised cells has been shown, indicating the existence of a cell surface receptor for C-peptide. C-peptide elicits a number of cellular responses, including Ca(2+) influx, activation of mitogen-activated protein (MAP) kinases, of Na(+),K(+)-ATPase, and of endothelial NO synthase. The pentapeptide EGSLQ, corresponding to the C-terminal five residues of human C-peptide, mimics several of the effects of the full-length peptide. The pentapeptide displaces cell membrane-bound C-peptide, elicits transient increase in intracellular Ca(2+) concentration and stimulates MAP kinase signalling pathways and Na(+),K(+)-ATPase. The Glu residue of the pentapeptide is essential for displacement of the full-length C-peptide, and free Glu can partly displace bound C-peptide, suggesting that charge interactions are important for receptor binding. Many C-peptide effects, such as phosphorylation of MAP-kinases ERK 1 and 2, stimulation of Na(+),K(+)-ATPase and increases in intracellular calcium concentrations are inhibited by pertussis toxin, supporting interaction of C-peptide with a G-protein-coupled receptor. However, all C-peptide effects cannot be explained in this manner, and it is possible that additional interactions are involved. Combined, the available observations show that C-peptide is biologically active and suggest a molecular model for its physiological effects.

Topics: Animals; C-Peptide; Diabetes Mellitus; Humans; Islets of Langerhans; Protein Structure, Secondary

Topics: Biomarkers; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Islets of Langerhans

Topics: Adult; Aged; Biomarkers; C-Peptide; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Female; Humans; Infections; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Patient Selection; Pregnancy

In recent years the physiological role of the proinsulin C-peptide has received increasing attention, focusing on the potential therapeutic value of C-peptide replacement in preventing and ameliorating type 1 diabetic complications. In order to consolidate these new data and to identify the immediate directions of C-peptide research and its clinical usefulness, an International Symposium was held in Detroit, Michigan, on October 20-21, 2000, under the auspices of the Wayne State University/Morris Hood Jr. Comprehensive Diabetes Center. In this communication, we review the cellular, physiological and clinical effects of C-peptide replacement in animal models and in patients with type 1 diabetes. Finally, recommendations are presented as to the most urgent studies that should be pursued to further establish the biological action of C-peptide and its therapeutic value.

Topics: Apoptosis; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus; Humans; Proinsulin; Sodium-Potassium-Exchanging ATPase

Topics: C-Peptide; Diabetes Mellitus; Diagnosis, Differential; Humans; Hypoglycemia

Topics: Amino Acid Sequence; Biomarkers; C-Peptide; Diabetes Mellitus; Humans; Immunoassay; Insulin; Insulinoma; Molecular Sequence Data; Pancreatic Neoplasms; Proinsulin; Protein Precursors

Topics: Biomarkers; C-Peptide; Diabetes Mellitus; Humans; Insulin Resistance

Proinsulin has generally been regarded as an inert precursor to insulin. However, over the past few years, proinsulin has established itself as a useful research tool for understanding how cells synthesize and secrete peptide hormones. Last year, proinsulin attracted renewed interest for its role as the precursor to C peptide, which may prove useful in the treatment of patients suffering from insulin-dependent diabetes mellitus. This mini-review focuses on three aspects of proinsulin, each of which attracted attention in 1997. These three aspects illustrate how this peptide hormone precursor may yet prove to be more important than its primary role as a prohormone, with only one bioactive product, would suggest.

Topics: Amino Acid Sequence; C-Peptide; Carboxypeptidases; Diabetes Mellitus; Molecular Sequence Data; Proinsulin; Protein Processing, Post-Translational

Short-term administration of physiological amounts of C-peptide to patients with insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in these patients as well as augment whole body glucose utilization. It could also be shown that C-peptide administration increases blood flow, oxygen uptake and capillary diffusion capacity of exercising forearm muscle in IDDM patients, probably by increasing capillary recruitment in the working muscle. Studies under in vitro conditions have shown that C-peptide stimulates glucose transport in skeletal muscle with its maximal effect within the physiological concentration range. The findings in a clinical study in which IDDM patients were given C-peptide and insulin or insulin alone for 4 weeks in a double-blind randomized study design, indicate that C-peptide improves renal function by reducing urinary albumin excretion and glomerular filtration, decreases blood retinal barrier leakage and improves metabolic control. Preliminary findings suggest that C-peptide administration on a short-term basis (3h) may ameliorate autonomic neuropathy by restoring to near normal the heart rate variability in response to expiration and inspiration. Insight into a possible mechanism of action of C-peptide is provided by the finding that C-peptide stimulates Na+K(+)-ATPase activity in renal tubular segments. In conclusion, the present results suggest that, contrary to the prevailing view, C-peptide possesses important physiological effects.

Topics: Animals; Awards and Prizes; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Double-Blind Method; Europe; Glucose; History, 20th Century; Humans; Insulin; Kidney; Muscles; Randomized Controlled Trials as Topic; Regional Blood Flow; Societies, Medical; Sweden

Topics: Animals; Biomarkers; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Kinetics; Models, Biological; Models, Theoretical

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Prognosis; Radioimmunoassay

Of the many information obtainable from the urine of diabetic patients, urinary C-peptide (CPR), albumin and anti-diuretic hormone (ADH) were representatively described using my clinical and experimental data. C-peptide excretion in 24h collection of urine is a good estimate of insulin secretion from the pancreas and thus low in IDDM patients and even in NIDDM patients at a later stage, but high in pathological conditions including Graves' disease, obesity, liver cirrhosis and Cushing's syndrome. Urinary albumin excretion in small amounts (microalbuminuria) is usually observed in diabetic patients who have been under a poor control state of diabetic hyperglycemia for over 5 years and provides a good tool for monitoring early diabetic nephropathy. The grade of microalbuminuria (30-300 mg/day) is positively correlated with the HbA1 level in diabetic patients, showing that microalbuminuria is reversible along with an improvement of diabetic control at least in an early phase of diabetic nephropathy. As the albumin level measured in a spot urine sample correlates well with the value in the 24h collection of urine, the albumin measurement is conveniently feasible with a spot urine sample at every patient's visit. The amount of ADH excreted in urine is 7-10% of that secreted from the posterior pituitary. The excretion of ADH in a day was in the urine of diabetic patients positively correlated with HbA1, urinary osmolarity and concentration of sodium in urine, although the pathological meaning of the observed ADH hypersecretion in the development of diabetic complications is currently unknown.

Topics: Albuminuria; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Vasopressins

The authors carried out a self-controlled study using 11, non-obese patients with impaired glucose tolerance. The first day an oral glucose tolerance test was performed as a control. This was repeated the next day with a simultaneous intake of 20 g natural wheat bran. On both days blood samples were taken at 30 minute intervals (for three hours period) after glucose or glucose plus bran ingestion to measure the plasma sugar, insulin, C-peptid, gastrin and glucagon levels. It has been found that: 1. With simultaneous bran intake the blood glucose levels were decreased as compared to the control values. 2. The serum insulin, and C-peptid levels were similar in both tests. 3. The glucagon response curve fell below that of the control. 4. The serum gastrin levels did not show any change following either glucose or glucose plus bran intake. It has been concluded, that the dietary fibres are able to decrease of glucagon release, beside their direct inhibitory effect on the level of sugar absorption from gastrointestinal tract.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Dietary Fiber; Gastrins; Glucagon; Glucose Tolerance Test; Humans; Insulin; Intestinal Absorption; Triticum

Artifactual hypoglycemia results from either improper collection of blood samples or interfering substances in the blood. Such artifacts should be easily detected and avoided. Factitious hypoglycemia, on the other hand, results from deliberate subterfuge by the patient and may thus elude proper diagnosis for some time. The most common cause of factitious hypoglycemia is surreptitious injection of insulin, and this is best diagnosed by the triad of hypoglycemia, inappropriately high insulin levels, and low C-peptide levels. Persons with diabetes may also intentionally misuse blood glucose strips to create the impression of hypoglycemia.

Topics: Adolescent; Adult; Blood Glucose; Blood Preservation; Blood Specimen Collection; C-Peptide; Diabetes Mellitus; Factitious Disorders; False Positive Reactions; Female; Glycolysis; Humans; Hypoglycemia; Insulin; Middle Aged; Sulfonylurea Compounds

Chronic pancreatitis (ChP) is the most frequent cause of pancreatogenous diabetes mellitus (DM). This kind of DM is a typical case of acquired insulin secretion deficiency. The group under scrutiny consisted of 122 patients with ChP. The average age of the 88 men was 42.9 and that of the 34 women was 54.4 years. According to pancreatography and to the presence of calcifications the patients were divided into four group by gravity of the morphological pictures at ERCP. The control group of healthy persons was made up of 15 men and 10 women. The presence of glucose intolerance was rated by the oral glucose tolerance test (oGTT) after 75 g glucose. The volume of endogenous secretion of insulin was studied by measuring IRI and C-peptide fasting and after stimulation. To measure the damage of pancreatic exocrine secretion we used function test (Spofagnost-Pankenzan test). In our own group of 122 patients we found decreased glucose tolerance in 72 (59%). 41% were cases of DM, 18% suffered from impaired glucose tolerance (IGT). As the results of stimulated C-peptide tests suggest, practically all patients with ChP corroborated by morphological changes in the pancreatic duct system at ERCP have decreased endogenous insulin secretion compared with healthy persons, and that includes even those normal glucose tolerance rated by results of oGTT We were able to prove a statistically significant relationship between the degree of morphological changes in the pancreatic duct system and the values of C-peptide. The mean values of the Spofagnost test showed significant differences between patients with normal glucose tolerance and DM.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

Topics: C-Peptide; Diabetes Mellitus; Humans

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Obesity; Physical Education and Training; Prediabetic State; Radioimmunoassay

Diabetes mellitus is a heterogeneous disorder. About 80% of the patients with this disease are categorized as having non-insulin-dependent diabetes mellitus, a disorder resulting from varied degrees of insulin resistance and impaired insulin secretion; the causes for these abnormalities are unknown. The remaining 15 to 20% of patients have insulin-dependent diabetes mellitus, a disorder caused by the destruction of insulin-producing endocrine cells within the pancreas and currently considered to be the result of an autoimmune process. During the course of both types of diabetes mellitus, the so-called long-term complications of diabetes invariably occur to some extent in all patients. These complications include retinopathy, nephropathy, neuropathy, and premature atherosclerosis. The molecular basis for these complications is not completely understood, but recent evidence obtained from both experiments in animals and prospective clinical studies indicates that metabolic derangements associated with poor glycemic control are a major determinant of the frequency and severity of these complications. Such evidence is the rationale for current attempts to maintain near-normal glycemia in patients with diabetes mellitus.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Diagnosis, Differential; Glucagon; Humans; Insulin; Insulin Resistance

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Islets of Langerhans; Proinsulin

Appropriate use of test strategies requires not only an appreciation of analytic considerations and the ability of the tests to confirm or exclude the hypotheses, but also an understanding of the underlying pathophysiology and clinical features of the problems to be addressed. This discussion covers disease definition, pathophysiology, analytic considerations, and strategies for diagnosis and management.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Insulin; Male; Pregnancy; Proinsulin

Topics: Adolescent; Adult; Animals; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Time Factors

Topics: Blood Glucose; C-Peptide; Clinical Competence; Clinical Laboratory Techniques; Diabetes Mellitus; Humans; Statistics as Topic; Tolbutamide

Topics: Adrenal Gland Diseases; C-Peptide; Diabetes Mellitus; Dwarfism; Glucagon; Growth Hormone; Humans; Insulin; Parathyroid Diseases; Radioimmunoassay; Thyroglobulin; Thyroid Diseases; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Hypoglycemia; Infant, Newborn; Insulin; Insulinoma; Islets of Langerhans; Kidney Function Tests; Middle Aged; Peptides; Radioimmunoassay

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Antagonists; Insulin Antibodies; Insulin Resistance; Islets of Langerhans; Proinsulin; Receptor, Insulin

This review reports the use of recombinant DNA techniques in the study of the structure and regulation of expression of insulin genes in man and experimental animals. Insulin biosynthesis by pancreatic islet cells is predominantly regulated by change in plasma glucose concentration. Using a cell-free protein synthesizing system as an assay of functional proinsulin messenger RNA (mRNA), and hybridization analysis with a cloned DNA complementary to proinsulin mRNA, it has been determined that through changes in proinsulin mRNA levels. Insulin genes of the rat, chicken and human have been isolated and sequenced. The 5' ends of the genes have similar sequences suggesting areas important for regulation of transcription. There are two non-allelic insulin genes in the rat, but only one in chickens and humans. Intervening sequences, areas of DNA transcribed into precursor mRNA but which do not appear in mature mRNA, have been described within insulin genes. The insulin gene resides on chromosome 11 of humans as determined by DNA hybridization analysis of mouse human hybrid cells. The structure of the insulin gene in genomic DNA of humans has been analyzed in diabetics and non-diabetics. Insertions of DNA between 1500 and 3400 base pairs have been detected near the transcription initiation site in 65% of type II diabetics, and 25-30% of non-diabetics (this difference is significant at the p less than 0.001 level). Limitation of these insertions to this potential promotor region of the insulin gene suggests that they may alter gene expression in type II diabetes. These insertions of DNA may prove to be useful genetic markers for diabetes.

Topics: Animals; Base Sequence; C-Peptide; Cloning, Molecular; Diabetes Mellitus; DNA; Fasting; Gene Expression Regulation; Genes; Humans; Insulin; Islets of Langerhans; Nucleic Acid Hybridization; Proinsulin; RNA, Messenger

Topics: Antibodies, Viral; Antigen-Antibody Complex; Autoantibodies; C-Peptide; Cross Reactions; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Enterovirus; HLA Antigens; Humans; Hyperthyroidism; Islets of Langerhans; Killer Cells, Natural; Receptors, Cell Surface; Risk; Thyroid Gland; Thyrotropin

Topics: C-Peptide; Diabetes Mellitus; Glyburide; Humans; Insulin; Insulin Secretion

The kinetics and the concentrations of B-cell peptides in plasma and urine are reviewed. Methodical problems in the determination of proinsulin, free and antibody-bound insulin and C-peptide are discussed, together with the possible application of these methods in the control of insulin-dependent diabetics.

Topics: Amino Acid Sequence; C-Peptide; Diabetes Mellitus; Insulin; Insulin Antibodies; Islets of Langerhans; Kinetics; Peptides; Proinsulin

The C-peptide is a polypeptide generated from enzymatic cleavage of proinsulin into insulin in pancreatic B. cell. C-peptide and insulin are secreted in an equimolar ratio. For this reason. C-peptide radio-immunoassay in blood or urine reflects the insulin secretion when direct insulin determination cannot be done (insulin treatment, circulating insulin antibodies). This assay is mainly used in clinical and investigational studies of insulin dependent diabets. It enabled demonstation of residual secretion of insulin in numerous insulin dependent patients (70% during the first year and 15% after the 15th year of the disease). Persistence of insulin secretion may play a role in the natural history of diabetes since patients with detectable C-peptide immunoreactivity have more stable diabetes, are controlled by lower insulin dose and are less ketosis prone than the others. Factors which influence persistence of B. cell activity in some IDD remain unknown.

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Peptides; Proinsulin; Radioimmunoassay

In two groups of pts with diabetic derangements the effect of infusion therapy was investigated with regard to metabolic and endocrine functions. The rate of infusion was adapted to the height of the central venous pressure and the administration of electrolytes to their serum concentration. Insulin was withheld until no further decrease of blood glucose was noted. Group A consisted of 8 pts with severe diabetic ketoacidosis (blood glucose higher than 25 mmol/l, pH below 7.0 and/or bicarbonate below 10 mmol/l). The duration of insulinfree rehydration was 8.8 +/- 1.3 (x +/- SE) hrs and the fluid retention 4060 +/- 3 633 ml. The osmolality in serum decreased from 356 +/- 12 to 340 +/- 8 mosm/kg H2O and the blood glucose from 37.9 +/- 2.9 to 28.6 +/- 3.4 mmol/l. No correlation existed between the decrease of blood glucose and the expansion of the intravascular volume. Therefore, the decrease of blood glucose was not caused by a simple dilution effect. High renal glucose excreation was observed (408 +/- 83 mmol) but could not explain the decrease of blood glucose. The glucose clearance fell from 25.9 +/- 6.9 to 21.5 +/- 3.8 ml/min/1.73 m2 body surface from the first to the last 2-hr periods. It must be concluded that the initial rehydration deminished gluconeogeneses and/or increased tissue glucose utilization without exogenous insulin administration. This conclusion is supported by the decrease in the plasma concentration of the contrainsular hormons. Glucagon decreased 579 +/- 209 to 319 +/- 88 pg/ml (n.s.). Cortisol from 49.9 +/- 4.6 to 35.8 +/- 6.7 micrograms/100 ml (p < 0.05) and Adrenalin from 2.43 +/- 1.03 to 0.4 +/- 0.22 ng/ml (p < 0.05). Blood gas analysis revealed only minimal and ketobodies in serum no changes. Therefore, it can be concluded that rehydration and decrease of plasma concentration of contrainsular hormones do not influence the enhenced lipolyses in diabetic ketoacidosis. Group B consisted of 8 pts with nonacidotic diabetic derangements (blood glucose higher than 25 mmol/l, pH above 7.3 and/or bicarbonate above 18 mmol/l) and an acute weightloss of more than 3 kg. The insulinfree rehydration lasted 13 +/- 1.6 hrs and the fluid retention was 4620 +/- 380 ml. The serum osmolality decreased from 317 +/- 5.3 to 288 +/- 1.9 mmol/l. The decrease of blood glucose could not be explained by delution effect. The renal glucose excreation was 370 +/- 120 mmol/l in total and the glucose clearance decreased from 15.3 +/- 8.4 to 8.0 +/- 2.8 ml/min/1.

Topics: Acidosis; Adolescent; Adult; Aged; Aldosterone; Blood Glucose; C-Peptide; Diabetes Mellitus; Electrolytes; Epinephrine; Female; Glucagon; Gluconeogenesis; Glycosuria; Humans; Hydrocortisone; Hydrogen-Ion Concentration; Infusions, Parenteral; Insulin; Male; Middle Aged; Osmotic Pressure; Renin; Water-Electrolyte Balance

The capacity of the pancreatic beta cells to secrete insulin can be evaluated in vivo by measurement either of circulating immunoreactive insulin or of C peptide, a by-product of insulin synthesis. Evaluation of serum levels is complicated, however, by the variable degradation rates and distribution spaces of these peptides. Also, interpretation of peripheral vein concentrations of insulin, and perhaps C peptide, is more difficult because of hepatic catabolism. Quantitation of these peptides in the urine may provide an integrated measure of insulin secretion. In insulin treated diabetic patients who develop circulating insulin antibodies, beta cell secretory capacity may be assessed by C peptide measurement, or by techniques that allow separate determinations of "free" and "total" insulin. A variety of stimulatory tests may be used to investigate insulin secretory capacity.

Topics: Adult; Animals; Blood Glucose; C-Peptide; Child, Preschool; Diabetes Mellitus; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Insulin Secretion; Islets of Langerhans; Rats

Topics: Antigens; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Insulin; Insulin Antibodies; Radioimmunoassay

The availability of C-peptide measurement continues to provide new and useful information about the state of beta cell secretory function and the natural history of diabetes. Measurement of proinsulin is of value in the diagnosis of insulin-secreting tumors.

Topics: C-Peptide; Cross Reactions; Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Immunoassay; Peptides; Proinsulin

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Dietary Carbohydrates; Glucose Tolerance Test; Glycosuria; Humans; Insulin; Ketone Bodies; Lipid Metabolism; Proteins; Radioimmunoassay

Improvement in the sensitivity and specificity of the C-peptide immunoassay and studies of larger groups of patients have increased our knowledge of the importance of residual beta-cell function and its metabolic consequences in insulin-treated diabetic patients. During the first five to 10 years after the onset of diabetes mellitus residual beta-cell function is demonstrable in the majority of insulin-treated patients irrespective of the severity of the initial symptoms and only partly dependent on the patient's age at diagnosis. Residual beta-cell function facilitates good control. Stable patients have a higher C-peptide concentration in plasma than unstable ones, but unmeasurable C-peptide is not always associated with poor control. More data are needed before the full significance of an even minimal reserve of beta-cell function is elucidated. It also remains to be shown whether the reductive in beta-cell function in diabetic patients has a qualitative as well as quantitative component.

Topics: C-Peptide; Diabetes Mellitus; Humans; Islets of Langerhans; Kinetics; Peptides

Topics: Animals; C-Peptide; Diabetes Mellitus; Humans; Pancreatic Neoplasms; Peptides; Proinsulin; Radioimmunoassay; Rats

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Diabetes Mellitus; Female; Humans; Hypoglycemia; Insulin Antibodies; Male; Middle Aged; Pedigree; Peptides; Proinsulin

The recent work on proinsulin and C-peptide has been reviewed with major emphasis on the most significant findings since 1972. Proinsulin has now been established as the biosynthetic precursor of insulin in all species examined, including man, with a preproinsulin as a possible precursor of the prohormone. The conversion of proinsulin which appears to occur exclusively in the pancreas leads to equimolar production of insulin and C-peptide. Although proinsulin has a direct biologic effect which is one-tenth as much as that of insulin, C-peptide has no biologic activity on homologous or heterologous tissue and no ability to modify the action of insulin and/or proinsulin. Previous work on proinsulin immunoassay suggested that this prohormone, but not C-peptide, cross-reacts with insulin antiserum. On the other hand, in the C-peptide immunoassay, proinsulin but not insulin cross-reacts with the antiserum. Up to this time, therefore, it has not been possible to immunoassay human proinsulin or C-peptide specifically. The very recent work from the laboratory of Heding, however, has brought about major advances in this area in which human C-peptide and proinsulin can be separated in the plasma by the use of Sepharose particles. With this recent major advancement, it is now possible to measure human C-peptide specifically. This measurement has been shown to be a useful tool for the assessment of beta-cell function in diabetic patients treated with insulin and in insulinoma patients in whom endogenous C-peptide secretion is not suppressed with exogenous insulin-induced hypoglycemia. With the use of a specific enzyme which degrades insulin but not proinsulin, postprandial plasma proinsulin values have been measured in a large number of subjects under a variety of physiologic and pathologic conditions. These results, which are comparable to those obtained by the more laborious column chromatography, could be summarized as follows: (1) proinsulin values in lean, young normal subjects do not vary greatly in response to insulin secretagogues; (2) proinsulin secretion in response to glucose results in a greater percentage of proinsulin in the older age group than in the younger group; (3) in lean adult and juvenile diabetic patients, the percentage of proinsulin is not excessive, whereas obese diabetics and pregnant diabetics appear to secrete relatively greater proinsulin than their diabetic controls; and (4) whereas most hyperinsulinemic states (Cusing's syndrome, adul

Topics: Amino Acid Sequence; Animals; Antibodies; C-Peptide; Cattle; Cross Reactions; Diabetes Mellitus; Dogs; Endoplasmic Reticulum; Female; Guinea Pigs; Haplorhini; Horses; Humans; Hyperinsulinism; Insulin; Male; Mice; Molecular Conformation; Pancreas; Pancreatic Neoplasms; Peptides; Proinsulin; Rats; Structure-Activity Relationship; Swine; Terminology as Topic

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Proinsulin

Topics: Adenoma, Islet Cell; Amino Acid Sequence; C-Peptide; Diabetes Mellitus; Humans; Hypokalemia; Immunoassay; Insulin; Insulin Antibodies; Kidney; Pancreatic Neoplasms; Peptides; Proinsulin

Topics: C-Peptide; Diabetes Mellitus; Humans; Hypoglycemia; Insulin; Radioimmunoassay

The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).. The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.. In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.. ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Topics: Atorvastatin; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Clinical Protocols; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Metabolic Syndrome; Prospective Studies; Quinolines; Republic of Korea; Research Design; Risk Factors; Time Factors; Treatment Outcome

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Double-Blind Method; Female; Fragaria; Fruit; Glucose Tolerance Test; Humans; Inflammation; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Obesity; Oxidative Stress; Plant Extracts; Polyphenols; Vaccinium macrocarpon

The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.. The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.. Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.. It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.. ClinicalTrials.gov NCT01875575.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Case-Control Studies; Diabetes Mellitus; Double-Blind Method; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Young Adult

Current classification of diabetes mellitus (DM) is based on etiology and includes type 1 (T1DM), type 2 (T2DM), gestational, and other. Clinical and pathophysiological characteristics of T1DM and T2DM in the same patient have been designated as type 1.5 DM (T1.5DM).. The aim of this study was to classify pediatric patients with DM based on pancreatic autoimmunity and the presence or absence of overweight/obesity, and to compare the clinical, anthropometric, and biochemical characteristics between children in the different classes of DM.. A sample of 185 patients, recruited (March 2008-April 2015) as part of the Cohort of Mexican Children with DM (CMC-DM); ClinicalTrials.gov, identifier: NCT02722655. The DM classification was made considering pancreatic autoimmunity (via antibodies GAD-65, IAA, and AICA) and the presence or absence of overweight/obesity. Clinical, anthropometric and biochemical variables, grouped by type of DM were compared (Kruskal-Wallis or chi-squared test).. The final analysis included 140 children; 18.57% T1ADM, 46.43% T1BDM, 12.14% T1.5DM, and 22.86% T2DM. Fasting C-Peptide (FCP), and hs-CRP levels were higher in T1.5DM and T2DM, and the greatest levels were observed in T1.5DM (p<0.001 and 0.024 respectively).. We clearly identified that the etiologic mechanisms of T1DM and T2DM are not mutually exclusive, and we detailed why FCP levels are not critical for the classification system of DM in children. The findings of this study suggest that T1.5DM should be considered during the classification of pediatric DM and might facilitate more tailored approaches to treatment, clinical care and follow-up.

Topics: Adolescent; Autoantibodies; C-Peptide; C-Reactive Protein; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Infant; Male; Mexico; Pancreas

Oxidative stress plays an important role in pathogenesis of diabetes mellitus and its complications. Our previous study has shown glucose lowering effect produced by 3 months supplementation of Nigella sativa (NS) in combination with oral hypoglycemic drugs among type 2 diabetics. This study explored the long term glucose lowering effect (over one year) of NS in patients with type 2 diabetes mellitus on oral hypoglycemic drugs and to study its effect on redox status of such patients.. 114 type 2 diabetic patients on standard oral hypoglycemic drugs were assigned into 2 groups by convenience. The control group (n = 57) received activated charcoal as placebo and NS group (n = 57) received 2g NS, daily, for one year in addition to their standard medications. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), C- peptide, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione and thiobarbituric acid reactive substances (TBARS) at the baseline, and every 3 months thereafter were determined. Insulin resistance and β-cell activity were calculated using HOMA 2 calculator.. Comparison between the two groups showed a significant drop in FBG (from 180 ± 5.75 to 180 ± 5.59 in control Vs from 195 ± 6.57 to 172 ± 5.83 in NS group), HbA1c (from 8.2 ± 0.12 to 8.5 ± 0.14 in control VS from 8.6 ± 0.13 to 8.2 ± 0.14 in NS group), and TBARS (from 48.3 ± 6.89 to 52.9 ± 5.82 in control VS from 54.1 ± 4.64 to 41.9 ± 3.16 in NS group), in addition to a significant elevation in TAC, SOD and glutathione in NS patients compared to controls. In NS group, insulin resistance was significantly lower, while β-cell activity was significantly higher than the baseline values during the whole treatment period.. Long term supplementation with Nigella sativa improves glucose homeostasis and enhances antioxidant defense system in type 2 diabetic patients treated with oral hypoglycemic drugs.. Clinical Trials Registry-India (CTRI) CTRI/2013/06/003781.

Topics: Adult; Antioxidants; Blood Glucose; C-Peptide; Catalase; Diabetes Mellitus; Female; Glutathione; Humans; Hypoglycemic Agents; Insulin Resistance; Male; Middle Aged; Nigella sativa; Oxidative Stress; Plant Extracts; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

In patients with type 2 diabetes, but not type 1 diabetes, abnormal secretion of incretins in response to oral nutrients has been described. In healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study, we examined the effect of diet soda on gut hormones in youths with diabetes.. Subjects aged 12-25 years with type 1 diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (n = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water, followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C-peptide, GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide Tyr-Tyr (PYY) were measured for 180 min. Glucose and GLP-1 have previously been reported for the healthy control subjects.. GLP-1 area under the curve (AUC) was 43% higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes (P = 0.020), similar to control subjects (34% higher, P = 0.029), but was unaffected by diet soda in patients with type 2 diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically different between the two conditions in any group.. Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not affected by diet soda. The clinical significance of this increased GLP-1 secretion, and its absence in youths with type 2 diabetes, needs to be determined.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Carbonated Beverages; Child; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose; Humans; Male; Peptide YY; Young Adult

Posttransplantation diabetes mellitus (PTDM) is a frequent complication after allogeneic stem cell transplantation (allo-SCT), important for its negative impact on cardiovascular health. Risk factors for PTDM are not well defined. We conducted a prospective study to investigate the risk factors and incidence for PTDM in the first 100 days after allo-SCT. A total of 84 patients completed the study, 60% of whom developed PTDM. In a multivariate logistic regression model, pretransplantation c-peptide level (>3.6 ng/mL; odds ratio [OR], 5.9; 95% confidence interval [CI], 1.77-20.22; P = .004), unrelated donor allo-SCT (OR, 4.3; 95% CI, 1.34-14.2; P = .014), and peak steroid dose >1 mg/kg/day (OR, 5.09; 95% CI, 1.19-23.2; P = .035) were identified as independent predictors of PTDM. In addition, overall survival (OS) was inferior in patients with PTDM compared with those without PTDM (mean survival, 2.26 years vs 2.7 years; P = .021). Pretransplantation c-peptide level greater than the cohort median (>3.6 ng/mL) also was associated with inferior OS (mean, 1.7 years vs 2.9 years; P = .012). In a multivariate Cox proportional hazards model, high-risk disease (hazard ratio [HR], 2.34; 95% CI, 1.09-5.28; P = .029) and pretransplantation c-peptide level >3.6 ng/mL (HR, 1.05; 95% CI, 1.01-1.09; P = .013) were independent predictors of OS when adjusted for systemic steroids and regimen intensity. We suspect that diabetes mellitus in the immediate posttransplantation period may be mediated via an inflammatory pathway that contributes to insulin resistance in the host adipose tissue. Our study is the first to report the risk factors of early PTDM in patients undergoing allo-SCT and identifies pretransplantation c-peptide as an independent predictor of diabetes and survival.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Factors; Survival Rate; Time Factors; Transplantation, Homologous

Individuals with impaired glucose tolerance have increased proinsulin levels, despite normal glucose or C-peptide levels. In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo. Genetic and physiological studies suggest a role for the zinc transporter gene SLC30A8 in diabetes risk, possibly through effects on insulin-processing in beta cells. We hypothesised that the risk allele at the type 2 diabetes-associated missense polymorphism rs13266634 (R325W) in SLC30A8 would predict proinsulin levels in individuals at risk of type 2 diabetes and may modulate response to preventive interventions.. We genotyped rs13266634 in 3,007 DPP participants and examined its association with fasting proinsulin and fasting insulin at baseline and at 1 year post-intervention.. We found that increasing dosage of the C risk allele at SLC30A8 rs13266634 was significantly associated with higher proinsulin levels at baseline (p = 0.002) after adjustment for baseline insulin. This supports the hypothesis that risk alleles at SLC30A8 mark individuals with insulin-processing defects. At the 1 year analysis, proinsulin levels decreased significantly in all groups receiving active intervention and were no longer associated with SLC30A8 genotype (p = 0.86) after adjustment for insulin at baseline and 1 year. We found no genotype × treatment interactions at 1 year.. In prediabetic individuals, genotype at SLC30A8 predicts baseline proinsulin levels independently of insulin levels, but does not predict proinsulin levels after amelioration of insulin sensitivity at 1 year.

Topics: Adult; C-Peptide; Cation Transport Proteins; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Male; Metformin; Middle Aged; Polymorphism, Genetic; Proinsulin; Thiazolidinediones; Troglitazone; Zinc Transporter 8

To investigate the pathogenesis of distal pancreatectomy (d-Px)-induced diabetes in Korean patients, we investigated insulin secretory and sensitivity indexes obtained by oral glucose tolerance testing in 20 patients that had received d-Px (10 with d-Px-induced diabetes and 10 with normal glucose tolerance with d-Px [NGT d-Px]) and in 164 control subjects (77 with type 2 diabetes mellitus and 87 with NGT) that did not receive d-Px. The pancreatectomized subjects had lower fasting serum insulin, homeostasis model assessment of pancreatic beta-cell function (HOMA-beta) levels, and insulinogenic indices than the NGT controls. The HOMA-beta values of nonobese NGT d-Px- and d-Px-induced diabetic subjects were 73.7% and 38.7% of those for nonobese NGT controls, respectively, and HOMA-beta was significantly lower only for d-Px-induced diabetic subjects (P < .01). In obese subjects, the HOMA-beta values of obese d-Px-induced diabetic subjects were significantly lower than those of obese NGT controls (P < .05). The insulin sensitivity was significantly lower in nonobese type 2 diabetes mellitus controls than in nonobese NGT d-Px or in nonobese d-Px-induced diabetic subjects (P < .001 and .05, respectively). These results show that a reduced insulin secretory function is a typical feature of glucose homeostasis in distal pancreatectomized patients and that insulin secretory defect plays a major role in the development of diabetes in these patients. In addition, the study suggests that pancreatic resections of 60% or less and body mass index are not the main causes of diabetes onset after d-Px in this study.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipids; Male; Middle Aged; Pancreatectomy

The purpose of this study was to evaluate intraoperative glucose control.. Prospective unblinded study.. Tertiary care center.. Diabetic (n = 17) and nondiabetic (n = 23) patients undergoing elective cardiac surgery.. Diabetics received a modified insulin regimen consisting of a fixed rate infusion of regular insulin, 10 U/m2/h, and a variable infusion of D10W, adjusted to maintain glucose between 101 to 140 mg/dL.. Baseline glucose was higher in diabetics versus nondiabetics (mean +/- standard error of the mean: 203 +/- 27 v 117 +/- 3 mg/dL, p < 0.005). After baseline, insulin levels were increased in diabetics to 410 to 568 microU/mL. Corresponding insulin levels in nondiabetics were 12 to 40 microU/mL. Compared with baseline, glucose was decreased by 10% +/- 29% in diabetics during hypothermic cardiopulmonary bypass and increased by 21% +/- 30% in nondiabetics (p < 0.005). After discontinuation of bypass, glucose was lower in diabetics (137 +/- 12 mg/dL) versus nondiabetics (162 +/- 8 mg/dL, p < 0.005). Nine diabetics had adequate intraoperative glycemic control during hypothermic bypass (glucose 123 +/- 8 mg/dL, insulin 550 +/- 68 microU/mL, glucose infusion rate 1.87 +/- 0.29 mg/kg/min), 6 approached adequate control near the end of surgery (glucose 147 +/- 8 mg/dL, insulin 483 +/- 86 microU/mL, glucose infusion rate 0.35 +/- 0.05 mg/kg/min), and 2 never achieved control. Diabetics with elevated initial glucose >300 mg/dL did not achieve adequate glycemic control. Four diabetics (3 with renal failure) required injection of 50% dextrose after bypass for hypoglycemia.. Adequate glycemic control can be achieved in most diabetics during cardiac surgery using a modified insulin clamp technique provided initial glucose is <300 mg/dL.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Diabetes Mellitus; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Resistance; Intraoperative Complications; Lactic Acid; Male; Middle Aged; Prospective Studies; Tachycardia; Tumor Necrosis Factor-alpha

To study the effect of integrative Chinese and Western medicine (ICWM) on improvement of the islet beta cell function in treating patients with latent autoimmune diabetes mellitus in adults (LADA).. Eighty-four patients of LADA were randomly divided into 3 groups (20 in A, 33 in B and 31 in C), they were treated respectively with sulfonylurea, insulin and combination of insulin and Chinese medicine. The changes before and after treatment in blood glucose, glycohemoglobin and islet beta cell function were observed.. After treatment, the damaged islet beta cell function in Group A was not improved, the secrete peak value of C-peptide was still low and delayed in Group A, but in Group B and C, it shifted earlier, suggesting that a certain degree of improvement and recovery of islet beta cell function. The improving effect in Group C was better.. Chinese herbal medicine had effect in lowering blood glucose and improving islet beta cell function in patients with diabetes mellitus, and showed a synergistic and enhancing action when combined use with insulin. Early treatment of insulin or combination of insulin and Chinese medicine should be applied to patients with LADA.

Topics: Adult; Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus; Drugs, Chinese Herbal; Female; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Phytotherapy

To analyze the secretion of the insulin precursor proinsulin in patients with beta-thalassemia and its possible relation to iron overload.. We assessed fasting proinsulin, insulin, C-peptide and glucose levels from 34 patients with beta-thalassemia and 33 healthy controls. The correlation to age, body mass index, hepatic iron concentration, serum ferritin and serum AST was analyzed.. Fasting proinsulin (p < 0.002) and proinsulin-to-insulin ratio (p < 0.02) were significantly increased in patients with thalassemia irrespective of the degree of glucose tolerance. They correlated positively to serum ferritin, liver iron, patient age and serum AST (all p < 0.05).. Disproportionately elevated proinsulin levels in thalassemic patients indicate early beta-cell dysfunction due to siderosis. An additional biological significance of hyperproinsulinemia and its possible ability to predict long-term iron toxicity in these patients remain to be clarified.

Topics: Adolescent; Adult; beta-Thalassemia; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Iron; Iron Overload; Liver; Male; Proinsulin; Radioimmunoassay

Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 +/- 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity.. Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50-72) with BMI 23.1 kg/m(2) (20.3-25.5) and HbA(1c) 8.0% (6.9-11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41-62) with BMI 21.9 kg/m(2) (17.6-27.3) and HbA(1c) 7.8% (6.2-12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean +/- SEM) showed insulin resistance amounting to 1.9 +/- 0.3 and 1.7 +/- 0.5 in the two groups, respectively.. In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9-10.1) and 7.2 mmol/l (3.1-10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient.. We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Kinetics; Middle Aged; Pancreatitis; Peptide Fragments; Protein Precursors

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P<.03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection.

Topics: Blood Glucose; C-Peptide; Cyclosporine; Diabetes Mellitus; Glycated Hemoglobin; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus

Type 2 diabetes is caused by reduced insulin secretion and insulin resistance in skeletal muscle and liver. We tested the combination therapy with insulin aspart, rosiglitazone, and metformin with the purpose of treating all three defects in order to test the hypothesis that this "triple therapy" will normalize glucose metabolism.. Sixteen obese type 2 diabetic outpatients on human NPH or MIX (regular + NPH insulin) insulin twice daily were randomized to either triple therapy, i.e., insulin aspart (a rapid-acting insulin analog) at meals, metformin (which improves hepatic insulin sensitivity), and rosiglitazone (which improves peripheral insulin sensitivity), or to continue their NPH or MIX insulin twice daily for 6 months. Insulin doses were adjusted in both groups based on algorithms. HbA(1c), insulin dose, hypoglycemic episodes, insulin sensitivity (clamp), hepatic glucose production (tracer), and diurnal profiles of plasma glucose and insulin were used in evaluating treatment.. In the triple therapy group, HbA(1c) declined from 8.8 to 6.8% (P < 0.01) without inducing severe hypoglycemic events. Postprandial hyperglycemia was generally avoided, and the diurnal profile of serum insulin showed fast and high peaks without any need to increase insulin dose. In the control group, the insulin dose was increased by 50%, but nevertheless both HbA(1c) and 24-h blood glucose profiles remained unchanged. Insulin sensitivity improved in both skeletal muscle and the liver in the triple therapy group, whereas no change was observed in the control group.. We conclude that treatment of the three major pathophysiological defects in type 2 diabetic subjects by triple therapy significantly improved glucose metabolism in obese type 2 diabetic subjects.

Topics: Aged; Blood Glucose; Blood Pressure; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucose Clamp Technique; Glycated Hemoglobin; Glycolysis; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Male; Metformin; Middle Aged; Obesity; Rosiglitazone; Thiazolidinediones

Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion.. 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity.. A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after).. Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.

Topics: Acarbose; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Obesity; Placebos; Research Design

This study was designed to compare the efficacy of acute premeal administration of glipizide versus nateglinide in controlling postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes.. A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 diabetes were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg glipizide (30 min premeal), 120 mg nateglinide (15 min premeal), 10 mg glipizide plus nateglinide (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal.. The subjects were aged 56 +/- 2 years and were moderately obese (BMI 31 +/- 1 kg/m(2)), with a mean HbA(1c) of 7.4 +/- 0.4%. The peak postprandial glucose excursion above baseline was higher with placebo (6.1 +/- 0.5 mmol/l) than glipizide (4.3 +/- 0.6 mmol/l, P = 0.002), nateglinide (4.2 +/- 0.4 mmol/l, P = 0.001), or glipizide plus nateglinide (4.1 +/- 0.5 mmol/l, P = 0.001). The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with glipizide (6.9 +/- 2.4 mmol/h. l, P = 0.002), nateglinide (9.7 +/- 2 mmol/h. l, P = 0.004), or glipizide plus nateglinide (5.6 +/- 2.2 mmol/h. l, P < 0.001). Peak and integrated glucose excursions did not differ significantly between glipizide and nateglinide. However, by 4 h postmeal, plasma glucose levels were significantly higher with nateglinide (9 +/- 0.9 mmol/l) compared with the premeal baseline (7.8 +/- 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial glucose level after administration of glipizide (7.6 +/- 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with glipizide (1,556 +/- 349 pmol/h. l) than nateglinide (1,364 +/- 231 pmol/h. l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between glipizide and nateglinide.. Acute premeal administration of nateglinide or glipizide has equal efficacy in controlling postbreakfast hyperglycemia in type 2 diabetes when each drug is administered at the optimum time before the meal. Glipizide causes a more pronounced and sustained postmeal insulin secretory response compared with nateglinide. Glipizide facilitates the return to near-fasting glucose levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal hypoglycemia in drug-naive patients. The clinical decision to use glipizide versus nateglinide should be based on factors other than the control of postprandial hyperglycemia in type 2 diabetes.

Topics: C-Peptide; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glipizide; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Obesity; Postprandial Period

Our aim was to distinguish beneficial effects of B-cell rest from other effects of correction of hyperglycaemia. For this purpose we used diazoxide which reversibly blocks insulin secretion.. Eight obese (age 53 +/- 1 yr: BMI 33 +/- 2 kg/m2: 4 females) type 2 diabetic patients with poor metabolic control (HbA1c 8.7 +/- 0.9% ref.<5.2%) were studied twice after a randomly ordered treatment period of five days of intensive i.v. insulin treatment alone or i.v. insulin with peroral diazoxide (300 mg/day, divided into 3 doses). The glycaemic control was not altered between the two treatment periods. Insulin secretion was measured in response to i.v. glucose and arginine.. Insulin infusion was used to achieve close to identical degrees of glycaemia during the two treatment periods. Previous treatment with diazoxide was associated with a moderate 1.9 +/- 0.6 fold rise in insulin response to intravenous glucose (p=0.04) and 1.6 +/- 0.4 fold increased glucose potentiation of arginine-induced insulin secretion (GPAIS) (p=0.04). Conversely, after insulin alone there was no response to i.v. glucose and no change in GPAIS.. Short-term diazoxide treatment improved important parameters of B-cell function and these effects could be dissociated from confounding effects of changes in glycaemia. Consequently, the results indicate beneficial effects of B-cell rest.

Topics: Antihypertensive Agents; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diazoxide; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Obesity; Proinsulin; Regression Analysis; Triglycerides

The accumulation of Nxi-(carboxymethyl)lysine (CML), a product of glycoxidation and lipoxidation reactions, on tissue proteins is related to the formation and acceleration of diabetic and nondiabetic atherosclerotic lesions. Yet, little is known about the levels of circulating serum CML-containing protein in nondiabetic patients with clinical symptoms of advanced atherosclerosis. We measured the levels of immunoreactive CML in sera from non-diabetic patients with accelerated symptoms of coronary heart disease, from diabetic patients with no late complications, and from healthy individuals. Serum CML was significantly higher in non-diabetic patients with coronary heart disease than in healthy control subjects and was comparable to serum CML in patients with type 2 diabetes mellitus without late complications and coronary heart disease. In nondiabetic patients with coronary heart disease, a significant inverse correlation was found between serum levels of CML and proinsulin C-peptide, a marker of pancreatic beta cells activity that affects microvascular function. Serum levels of CML and high density lipoprotein (HDL) were positively correlated in this group. We conclude that glycoxidation and lipoxidation are associated with serum HDL levels and the secretive capacity of pancreatic beta cells in nondiabetic patients with coronary heart disease.

Topics: Arteriosclerosis; C-Peptide; Carbohydrate Metabolism; Cholesterol, HDL; Coronary Disease; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Humans; Islets of Langerhans; Lipid Metabolism; Lipoproteins, HDL; Lysine; Male; Middle Aged; Oxidation-Reduction

A weight-reducing effect of metformin has been demonstrated in obese subjects with and without diabetes. The mechanisms of this action are unclear, which may be partly due to the fact that in obese and diabetic patients the substance's effects result from a complex interaction with the distinct endocrine and metabolic disturbances in these patients. To dissociate primary from secondary action of metformin, we examined effects of the substance in normal-weight healthy subjects. Fifteen normal-weight men were treated with metformin (850 mg twice daily) or placebo for a 15-day period in a double-blind, placebo-controlled, cross-over study. Anthropometric, psychologic, cardiovascular, endocrine, and metabolic parameters were assessed before and at the end of the treatment period. Metformin did not affect body weight (P =.838) and body fat mass (P =.916). Yet, serum leptin concentration was distinctly reduced after metformin (P <.001). Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P <.001). There were no effects of metformin on feelings of hunger, blood pressure, heart rate, resting energy expenditure, the respiratory quotient, free fatty acids, beta-hydroxybutyrate, glycerol, triglycerides, cholesterol, and uric acid (all P >.1). Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.

Topics: Adipose Tissue; Adult; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Metformin; Obesity; Reference Values

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.

Topics: Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Pancreatitis; Peptide Fragments

An inconsistent association has been found between gallbladder disease and diabetes mellitus. We hypothesized that insulin resistance rather than diabetes status may be a primary factor involved in gallstone formation. A total of 5,653 adult participants in the third United States National Health and Nutrition Examination Survey without known diabetes underwent gallbladder ultrasonography and phlebotomy after an overnight fast for measurement of serum insulin, C-peptide, and glucose. Gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. Subjects were characterized as having normal fasting glucose (<110 mg/dL), impaired fasting glucose (110 to <126 mg/dL), or undiagnosed diabetes (>/=126 mg/dL). After controlling for other known gallbladder disease risk factors, among women, undiagnosed diabetes was associated with increased risk of gallbladder disease (prevalence ratio [PR] = 1.91, 95% confidence interval [CI] = 1.29-2. 83); whereas impaired fasting glucose was unassociated. Gallbladder disease risk in women increased with levels of fasting insulin (PR = 1.63, 95% CI = 1.11-2.40) and C-peptide (PR = 2.07, 95% CI = 1.32-3. 25) comparing highest to lowest quintiles. However, the association of gallbladder disease with undiagnosed diabetes was not diminished when the model included fasting insulin (PR = 1.85, 95% CI = 1.24-2. 77). In men, there was a statistically nonsignificant association with undiagnosed diabetes (PR = 2.11, 95% CI = 0.76-5.85), but no association of gallbladder disease with insulin or C-peptide. Among women higher fasting serum insulin levels increased the risk of gallbladder disease, but did not account for the increased risk in persons with diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Gallbladder Diseases; Humans; Insulin; Male; Middle Aged; Risk Factors; Sex Distribution

To characterize metabolic effects of troglitazone in type 2 diabetic, obese, and lean subjects, and examine the effects of troglitazone 2-3 weeks after discontinuation.. Nine type 2 diabetic, nine obese, and nine lean subjects underwent baseline metabolic studies including an 8-h meal-tolerance test (MTT) and a 5-h glucose clamp. Subjects then received troglitazone (600 mg/day) for 12 weeks and subsequently had repeat metabolic studies. Diabetic subjects remained off hypoglycemic agents for 2-3 weeks and then underwent a 5-h glucose clamp.. In diabetic subjects, fasting plasma glucose was reduced (P<0.05) and insulin-stimulated glucose disposal (Rd) was enhanced by treatment (P<0.02). The area under the MTT 8-h plasma glucose curve declined with therapy (P<0.001), and its change was positively correlated with the improvement in Rd (r = 0.75, P<0.05). There was also a positive correlation between the change in fasting hepatic glucose output (HGO) and the change in fasting plasma glucose with treatment (r = 0.92, P<0.001). Discontinuation of therapy for 2-3 weeks did not significantly affect fasting plasma glucose or insulin-stimulated glucose Rd. In obese subjects, insulin-stimulated glucose Rd improved with therapy (P<0.001), allowing for maintenance of euglycemia by lower plasma insulin concentrations (P<0.05). In lean subjects, an increase in fasting HGO (P<0.001) and glucose clearance (P<0.01) was observed.. Troglitazone lowers fasting and postprandial plasma glucose in type 2 diabetes by affecting both fasting HGO and peripheral insulin sensitivity. Its effects are evident 2-3 weeks after discontinuation. In obese subjects, its insulin sensitizing effects suggest a role for its use in the primary prevention of type 2 diabetes.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Thiazoles; Thiazolidinediones; Troglitazone

Unlike other pharmacological therapies used in obese type 2 diabetic patients, metformin has been shown to improve glycemic control with lower insulin levels and not to involve weight gain. We therefore examined the effect of adjunct metformin in 13 severely obese type 2 diabetic patients (BMI 39.3 +/- 3.9 kg/m2) in suboptimal glycemic control pretreated with intensified insulin therapy. Patients were randomly assigned to either metformin or placebo treatment (double-blind) for 10 weeks and after a 2 week washout period received the opposite treatment, respectively, for 10 additional weeks. HbA1c decreased comparably during placebo (from 8.1 +/- 0.4 to 7.6 +/- 0.3%) and metformin (from 8.5 +/- 0.4 to 7.4 +/- 0.3%, p = 0.29 vs. placebo). Changes in fasting glucose levels were also not different between placebo (from 9.3 +/- 0.7 to 9.5 +/- 0.7 mM) and metformin (from 10.3 +/- 0.5 to 9.5 +/- 0.6 mM, p = 0.44 vs. placebo). Total exogenous insulin requirements decreased from 53 +/- 10 to 35 +/- 7 units during metformin treatment (p = 0.02 vs. placebo). Changes in fasting insulin levels during placebo and metformin treatments were not different (p = 0.11). Metformin had no effect on body weight and serum triglycerides but marginally decreased serum cholesterol levels (from 239 +/- 18 to 211 +/- 14 mg/dl, p = 0.005, p = 0.08 vs. placebo). During the oral glucose tolerance test no differences were observed in the areas under the curve for glucose and insulin while that for C-peptide showed a tendency to increase during metformin administration. We conclude that addition of metformin to insulin treatment in severely obese type 2 diabetic patients improves glycemia but not hyperinsulinemia in comparison to intensive insulin therapy alone. With adjunct metformin, approximately 30% less exogenous insulin is required. With respect to glycemia and lipids, adjunct metformin can be a reasonable treatment alternative in selected obese patients with type 2 diabetes already on intensive insulin therapy.

Topics: Body Mass Index; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipoproteins; Male; Metformin; Middle Aged; Obesity; Placebos; Triglycerides

The insulin-sensitizing action of troglitazone may be mediated through the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the promotion of preadipocyte differentiation in adipose tissue on which troglitazone has depot-specific effects. We investigated the relationship between efficacy of the drug and body fat distribution. Changes in body fat distribution were also investigated by long-term administration of the drug.. Troglitazone was given at a dose of 400 mg/day to 20 patients with type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid levels, and body weight were measured monthly Body fat distribution was evaluated in subcutaneous (SC) and visceral fat using a computed tomography scan at umbilical levels before and after troglitazone therapy. During the 1-year troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to 7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01). Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c) during treatment showed a significant negative correlation with SC fat area (r = -0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone treatment resulted in increased accumulation of SC fat without a change in visceral fat area and, consequently. in a significant decrease in the visceral-to-SC fat ratio.. Predominant accumulation of SC fat for the visceral fat tissue was an important predictor of the efficacy of troglitazone therapy in patients with type 2 diabetes. Greater efficacy of troglitazone was observed in women who were characterized by more accumulation of SC adipose tissue than men. Long-term administration of the drug resulted in weight gain with increased accumulation of SC adipose tissue, probably because of the activation of PPAR-gamma in the region.

Topics: Adipose Tissue; Body Mass Index; C-Peptide; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Sex Characteristics; Thiazoles; Thiazolidinediones; Tomography, X-Ray Computed; Troglitazone; Viscera; Weight Gain

The induction of diabetes has been recognised as adverse effect of the immunsuppressive drug FK506/Tacrolimus. The aim of this study was to clarify whether insulinopenia or insulin resistance dominates and whether islet cell autoantibodies are present in patients treated by FK506. We investigated 58 patients 1-3 years after liver transplantation while under therapy with FK506 or CsA and prednisolone (0-7.5 mg) for basal blood glucose levels and islet-cell specific autoantibodies. A subgroup of 20 patients on FK506, 10 patients on cyclosporin and 15 healthy volunteers were metabolically tested by oGTT. Five patients had diabetes pre-transplantation. After transplantation, 9/28 FK506-treated patients developed newly diagnosed diabetes compared to 0/25 cyclosporin-treated patients (p<0.01). Both patient groups showed significantly higher fasting blood glucose, insulin or C-peptide levels compared to controls. Through the oGTT, FK506-treated patients without diabetes, but not cyclosporin-treated patients, had higher C-peptide levels compared to controls (p<0.05). Five/32 patients on FK506 compared to 0/26 patients on cyclosporin (p<0.05) had islet cell specific autoantibodies, mainly ICA without GAD- or IA2-Ab, a feature described for latent autoimmune diabetes in adults. ICA positivity was correlated to the diabetes associated HLA haplotype DR4/DQ*0302 (p<0.05). Although the interpretation of our metabolic data in patients with concomitant liver disease and prednisolone therapy has limitations, we suggest insulin resistance caused by treatment with FK506. However, manifestation of diabetes was associated with relative insulinopenia rather than insulin resistance in patients on FK506. Immunsuppressive therapy by FK506 was not able to suppress islet cell autoimmunity, and may even induce it in genetically predisposed patients.

Topics: Adult; Autoimmunity; Blood Glucose; C-Peptide; Cyclosporine; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Islets of Langerhans; Lipids; Liver Transplantation; Male; Middle Aged; Tacrolimus

When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers.. This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia.. The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups.. Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Topics: Adult; Alleles; Autoantibodies; Black People; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Genotype; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunogenetics; Insulin; Insulin Secretion; Male; Obesity

To determine the effect of benfluorex on glycaemic control in obese insulin-requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated after a 1-month run-in followed by a 3-month double-blind treatment period (3 tablets daily) with benfluorex (B; n = 37) vs placebo (P; n = 39). At inclusion, the B and P groups respectively did not differ in body weight (80.9 +/- 10.3 vs 77.2 +/- 9.1 kg), body mass index (BMI) (30.1 +/- 4.6 vs 29.0 +/- 2.3 kg/m2) or fasting blood glucose (11.22 +/- 4.33 vs 10.35 +/- 4.42 mmol/l). However, daily insulin dose and HbA1c levels were higher in the B group (59.9 +/- 18.6 vs 50.4 +/- 12.8 IU, p = 0.012; and 7.72 +/- 1.60 vs 6.96 +/- 1.27%, p = 0.025, respectively). After 3 months of treatment, the decrease in daily insulin dose was greater in the B group (8.7 +/- 10.1 vs 2.7 +/- 8.1 IU; p = 0.032), with a decrease in HbA1c (-0.73 +/- 1.74%, p = 0.026), vs no change in the P group (+0.01 +/- 1.65%, NS) and a tendency towards a greater decrease in fasting blood glucose (-1.43 +/- 5.41 vs +0.42 +/- 3.78 mmol/l respectively). Body weight and BMI were also lower in the B group (1.77 ñ 2.27 vs 0.21 ñ 2.68 kg, p = 0.013; and 0.64 +/- 0.84 vs 0.07 +/- 1.07 kg/m2, p = 0.019, respectively) in parallel with the decrease in insulin dose. Triglycerides decreased in the B group vs an increase in the P group (-0.54 +/- 2.04 vs +0.21 +/- 0.70 mmol/l p = 0.06). Total cholesterol decreased within the B group (-0.47 +/- 1.01 mmol/l; p = 0.013) and vs the P group (intergroup p = 0.006). Adverse events were reported in 11 patients in the B group vs 5 in the P group (NS), causing dropout in only one case (intercurrent illness, P group). Addition of benfluorex in obese insulin-requiring Type 2 diabetes thus enhances glycaemic control and lowers both daily insulin requirement and body weight. Benfluorex + insulin is a valid alternative for obese patients who remain poorly controlled despite insulin or who require high doses of insulin.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Fenfluramine; Humans; Hypolipidemic Agents; Insulin; Insulin Resistance; Male; Middle Aged; Monitoring, Physiologic; Obesity; Postprandial Period

To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat, high-carbohydrate (CHO) hypocaloric diet.. Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO, respectively. Fasting blood samples were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time: time required to induce in vitro formation of conjugated dienes).. At baseline, there were no differences between the groups in plasma lipids, lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL, triglycerides, and apolipoproteins A and B (P < 0.05), but the MUFA group manifested a greater decrease in total cholesterol, triglycerides, and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group (P < 0.05). Improvements in these parameters were sustained during refeeding. After dieting, lag time was prolonged in the MUFA group (208 +/- 10 min) compared with the CHO group (146 +/- 11 min; P < 0.05). Lag time was prolonged further during refeeding in the MUFA group (221 +/- 13 min, P = 0.10), while the CHO group remained unchanged (152 +/- 9 min, P < 0.05). Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding (r = 0.74 and r = 0.93, respectively; both P < 0.001).. Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes.

Topics: Apolipoproteins; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Carbohydrates; Dietary Fats, Unsaturated; Energy Intake; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Regression Analysis; Risk Factors; Triglycerides; Weight Loss

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Topics: Adult; C-Peptide; Coenzymes; Deafness; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; DNA, Mitochondrial; Family Health; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Hearing; Humans; Lactic Acid; Male; Middle Aged; Mothers; Point Mutation; Time Factors; Treatment Outcome; Ubiquinone

This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone.. This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events.. FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.. Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Topics: Aged; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Patient Dropouts; Sulfonylurea Compounds; Treatment Outcome; Triglycerides

Hypoglycemia is a serious complication of therapy for diabetes. Chronic hypoglycemia and the attendant decrease in quality of life have been rationales for advocating pancreas transplantation as an alternative treatment. However, reports have appeared that suggest that as high as 30-50% of pancreas transplant recipients have occasional symptoms of mild hypoglycemia. Therefore, we studied glucose and hormone levels in transplant recipients and healthy control subjects.. We studied glucose and hormone levels in transplant recipients reporting frequent symptoms of hypoglycemia (n = 10), transplant recipients without symptoms of hypoglycemia (n = 9), and healthy control subjects (n = 8) after a mixed meal and during a subsequent 24-h modified fast. All transplant recipients were insulin-independent; were receiving prednisone, cyclosporine, and azothioprine; and had functioning grafts with systemic venous drainage.. No significant differences were observed in the fasting glucose, insulin, C-peptide, or glucagon levels when comparing the symptomatic with the asymptomatic groups of patients who had undergone successful pancreas transplantation. Similarly, no significant differences were found in the immediate postprandial period after a mixed meal. However, during the subsequent 24-h fast, glucose levels fell lower in the symptomatic than in the asymptomatic group of patients receiving a transplanted pancreas (71+/-2 vs. 81+/-2 mg/dl, P < 0.002). During the fast, no significant differences were found in insulin, C-peptide, or glucagon levels when comparing asymptomatic to symptomatic groups. Of 10 symptomatic recipients of pancreas transplantation, 5 reported symptoms of hypoglycemia during the study. In four of these five subjects, the onset of symptoms corresponded to nadirs in serum glucose, which occurred at values 2 SD or more below the mean glucose observed for the control and the asymptomatic pancreas recipient groups. The serum glucose levels at the time of symptoms in these four subjects were 55, 66, 51, and 57 mg/dl. In each of these four subjects, symptoms abated and the glucose levels rose spontaneously without intervention. One of these four subjects had elevated insulin binding activity in his serum consistent with endogenous insulin antibodies. This individual had a serum glucose value of 55 mg/dl at the conclusion of the 24-h fast without symptoms.. Among a group of pancreas transplant recipients reporting frequent symptoms of hypoglycemia, some individuals demonstrated transient, symptomatic postprandial hypoglycernia. With the exception of one recipient with insulin antibodies, no evidence was found for hypoglycemia during fasting. Although postprandial hypoglycemia may occur in some pancreas transplant recipients, it does not appear to be a highly significant clinical problem.

Topics: Activities of Daily Living; Adult; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Humans; Hypoglycemia; Insulin; Male; Pancreas Transplantation; Postprandial Period; Quality of Life

Topics: Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Lipoprotein(a); Male; Metformin; Middle Aged; Retrospective Studies

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Topics: Adipose Tissue; Administration, Oral; Adult; Blood Glucose; C-Peptide; Carnitine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Fatty Acids; Fatty Acids, Nonesterified; Female; Glucagon; Glycerol; Humans; Hydroxybutyrates; Ketones; Liver; Male; Triglycerides

It is difficult to treat obese non-insulin-dependent diabetic patients (NIDDs) whose glycaemic control remains poor despite maximal oral antidiabetic therapy. We studied the effect of a continuous subcutaneous insulin infusion (CSII) associated with a low-calorie diet and metformin 1,700 mg/day on glycaemic control and basal and stimulated insulin secretion in a series of 82 overweight NIDD before (T1), during CSII (T2), and after CSII withdrawal (T3). Patients were treated for 8 to 23 days with a mean amount of 0.50 +/- 0.02 IU/kg/day. Glycaemic control was very good after 3-5 days of CSII and remained good at T3. At T2, fasting and postprandial plasma C peptide levels decreased significantly. At T3, fasting C peptide was very similar to T1, and postprandial C peptide was significantly higher than at T1. The molar fasting and postprandial plasma C peptide/glycaemia ratios increased significantly at T3. After glucagon injection, the molar delta C peptide/glycaemia ratio was significantly increased at T2 and even higher at T3. At T2, as at T1 and T3, there were significant correlations between fasting and postprandial C peptide levels and between the glucagon-induced C peptide peak and fasting and postprandial C peptide levels. Between T1 and T3 weight changes correlated significantly with the molar fasting C peptide/glycaemia ratio at T1. Twenty-nine of the 30 patients for whom this ratio was > 6.6 x 10(-8) lost weight. The length of CSII treatment did not correlate with weight changes or other biological parameters. This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity. These results were obtained in only 8 to 10 days.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Parenteral; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Secretory Rate; Time Factors

Many newly diagnosed obese African-American patients with history of severe hyperglycemia or diabetic ketoacidosis (DKA) are able to discontinue pharmacological treatment with continued good metabolic control. However, many of these individuals relapse into hyperglycemia within 1 year. In such patients, we compared the effect of low-dose sulfonylurea and dietary therapy in the prevention of recurrence of hyperglycemia.. We conducted an intention-to-treat study in 35 obese newly diagnosed diabetic patients (17 with DKA and 18 with severe hyperglycemia). After discontinuation of insulin, seven of 17 patients with DKA and seven of 18 patients with hyperglycemia were managed with diet and glyburide (1.25-2.5 mg/day), whereas other patients were followed with diet alone. In all patients, pancreatic insulin reserve was documented 1 day after resolution of hyperglycemic crises and within 1 week of discontinuation of insulin. Recurrence of hyperglycemia was defined as fasting blood glucose > 7.8 mmol/l (140 mg/dl) or random blood glucose > 10 mmol/l (180 mg/dl) on two or more consecutive determinations, or HbA1c > 7.5%.. Both treatment groups were comparable in age, sex, duration of diabetes, months of insulin therapy, BMI, glucose, and HbA1c. At presentation, the acute C-peptide response to glucagon in obese DKA patients was lower than in patients with hyperglycemia (P < 0.01), but responses were comparable after discontinuation of insulin. Sulfonylurea treatment significantly reduced recurrence of hyperglycemia in both obese DKA and obese hyperglycemic patients (P = 0.03). With a median follow-up of 16 months, hyperglycemia recurred in six of 10 DKA patients and in five of 11 hyperglycemia patients treated with diet alone, compared with one of seven DKA and one of seven hyperglycemia patients treated with glyburide. Readmission with metabolic decompensation occurred in four patients treated with diet but in none of the patients treated with diet and glyburide.. Low-dose sulfonylurea therapy prevents recurrence of hyperglycemia in newly diagnosed obese African-American patients with a history of hyperglycemic crises.

Topics: Adult; Black or African American; Black People; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diet, Diabetic; Female; Georgia; Glyburide; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Middle Aged; Obesity; Recurrence

High intake of trans fatty acids and saturated fatty acids (SFAs) is known to increase the risk of coronary heart disease. We studied the effects of diets enriched in various fatty acids on postprandial insulinemia and fasting serum levels of lipids and lipoproteins in obese patients with NIDDM.. Sixteen obese NIDDM patients were studied in a free-living outpatient regimen. After a run-in period, the patients received three different isocaloric diets for 6 weeks using a randomized crossover design. The patients were instructed to keep the energy intake from carbohydrate and protein constant at 50 and 20 E% (percent of energy intake), respectively, on all three diets. The fat composition of the diets differed: saturated fat (SAT) diet (20 E% SFAs, 5 E% polyunsaturated fatty acids [PUFAs], and 5 E% monounsaturated fatty acids [MUFAs]) versus cis monounsaturated fatty acid (CMUFA) diet (20 E% cis-MUFAs, 5 E% PUFAs, and 5 E% SFAs) versus trans monounsaturated fatty acid (TMUFA) diet (20 E% trans-MUFAs, 5 E% PUFAs, and 5 E% SFAs). Fasting serum levels of lipids and lipoproteins were measured at baseline and in the fasting state before meal tolerance tests at the end of each study period. Insulin secretion was assessed from incremental serum insulin and C-peptide responses during the meal tests.. BMI, waist-to-hip ratio, and glycemic control remained stable throughout the study. After meal stimulation, postprandial glycemic responses were similar on all diets; however, serum insulin and C-peptide responses were greater following the TMUFA and SAT diets than following the baseline or CMUFA diets (P < 0.05). No statistical difference was found in fasting levels of serum lipids (total cholesterol, triglyceride, phospholipid, and nonesterified fatty acids) or lipoproteins of HDL cholesterol, VLDL cholesterol, LDL cholesterol, and apolipoprotein B between diets.. In the presence of unchanged glycemia, both dietary trans fatty acids and SFAs induce an increase in postprandial insulinemia in obese patients with NIDDM.

Topics: Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Humans; Insulin; Insulin Secretion; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Postmenopause; Random Allocation; Time Factors

This study compared the effect of mild exercise while fasting on plasma glucose concentrations in subjects with NIDDM treated with extended-release glipizide and subjects not taking an oral hypoglycemic agent.. Twenty-five moderately obese subjects with NIDDM were randomized to treatment with extended-release glipizide or placebo. After 9 weeks of treatment, they fasted overnight, took their study drug, omitted breakfast, and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide concentrations were measured before, during, and after exercise.. On the fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241 mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended-release glipizide group. The decrement of glucose from the fasting baseline was modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms.. Chronic use of extended-release glipizide does not enhance the hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine lifestyle treatments for NIDDM may be continued during ongoing use of this agent.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Exercise; Exercise Test; Female; Glipizide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Time Factors

The hormonal responses to, and symptoms of, hypoglycaemia were investigated in 19 diabetic children (mean age 14.2 (SD 1.4) years, mean HbA1c 9.8 (SD 1.2)%) and 16 non-diabetic children (14.4(1.0) years) during a gradual reduction in plasma glucose with the glucose clamp technique. Plasma glucose was reduced from approximately 5.7 to approximately 2.6 mmol l(-1) in the diabetic children and from approximately 5.7 to approximately 2.9 mmol l(-1) in the non-diabetic children over 200 min. The mean glycaemic thresholds for adrenaline, and for autonomic and total symptom score, were similar in the diabetic and non-diabetic groups, and were found at plasma glucose levels between 3.4 and 3.7 mmol l(-1). The mean glucose levels which elicited increase of cortisol, growth hormone, and glucagon were lower (p < 0.01), and the mean incremental responses of adrenaline, cortisol, and glucagon were smaller in the diabetic than in the non-diabetic children. In the diabetic children, a correlation was found between Body Mass Index (BMI) and the hypoglycaemic thresholds for autonomic and total symptom scores (r = 0.64, p < 0.01 and r = 0.72, p = 0.001, respectively). We conclude that counterregulatory hormone responses are attenuated in diabetic as compared to non-diabetic children, whereas recognition of autonomic symptoms is similar in the two groups. Diabetic children with a higher BMI seem to have increased awareness of a declining plasma glucose level.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Epinephrine; Female; Glucagon; Glucose; Glucose Clamp Technique; Glycated Hemoglobin; Growth Hormone; Hormones; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Norepinephrine; Time Factors

We student basal, glucose- and glucagon-induced insulin secretion in non-insulin diabetes mellitus (NIDDM) patients in relation to body mass index (BMI) and fasting serum glucose (FBS) level. A total of 46 NIDDM patients and 22 control subjects with varying degrees of BMI and FBS were given 100 g of oral glucose and 1 mg of intravenous glucagon on separate days. C-peptide response to glucose, but not basal serum C-peptide and C-peptide response to glucagon, was significantly lower in NIDDM than in controls (P < 0.001). FBS was inversely correlated with C-peptide response to glucose in NIDDM patients (r = -0.67, P < 0.001), but not with basal C-peptide level and C-peptide response to glucagon. On the other hand, BMI was positively correlated with basal serum C-peptide level both in NIDDM (r = 0.60, P < 0.001) and in control subjects (r = 0.74, P < 0.001). In 15 poorly controlled NIDDM patients, the tests were repeated after insulin treatment for 10-14 days. C-peptide response to glucose significantly increase, but not to a level in control subjects, after glycemic control. Basal serum C-peptide level and the C-peptide response to glucagon decreased after glycemic control to significantly lower levels than those in the baseline and those in control subjects. These results suggest that beta cell secretory reserve is reduced in moderate to severe NIDDM patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Injections, Subcutaneous; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values

We studied the effects of continuous subcutaneous infusion of octreotide (100 micrograms/day for 5 days) on glycaemic values, counterregulatory hormones secretion, hepatic glucose production (HGP) and glucose disposal during an euglycaemic clamp in 7 C-peptide-negative type 1 diabetic patients and 7 C-peptide positive insulin-treated type 2 diabetic patients. In type 1, but not type 2 diabetic patients, octreotide significantly reduced glycaemic values (P < 0.005) and also diminished HGP during an euglycaemic clamp (P < 0.05). However, insulin stimulated global glucose uptake remained unchanged. GH, glucagon, IGF-I, IGFBP-3 levels, were significantly lowered by octreotide in both type 1 and type 2 diabetic patients whereas cortisol and epinephrine remained unmodified. Moreover in type 2 diabetic patients both basal (P < 0.05) and after-meal (P < 0.01) C-peptide secretion was reduced by octreotide. These data point to different metabolic effects of octreotide in type 1 versus type 2 diabetic patients with the drug only being able to reduce glycaemic values and HGP in the former but not in the latter subjects. The failure of octreotide to diminish glycaemic values and HGP in type 2 diabetic patients in spite of its ability to lower GH and glucagon may probably depend on temporary blockage of residual endogenous insulin secretion induced by octreotide administration.

Topics: Adult; Antineoplastic Agents, Hormonal; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucose; Hormones; Humans; Hyperglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Liver; Male; Middle Aged; Octreotide

Although moderate weight loss improves glycemic control in obese NIDDM patients, quite often it is not normalized. To determine whether the response to weight loss can be improved by altering the macronutrient composition of hypocaloric diets, 17 obese NIDDM patients were studied at I) baseline, 2) after dieting for 6 weeks on a formula diet enriched in either monounsaturated fatty acids (MUFAs, n = 9) or carbohydrates (CHOs, n = 8) at a 50% caloric deficit, and 3) after 4 weeks of postdiet refeeding on the respective formulas with caloric intake titrated to achieve weight maintenance. Fasting, 24-h, and oral glucose tolerance test (OGTT) blood glucose, plasma insulin, and C-peptide levels were measured. All prediet parameters were similar between groups. After dieting, although weight loss was similar between groups, the fasting glucose level decreased significantly more in the MUFA group (-4.6 +/- 0.7 mmol/l) than in the CHO group (-2.4 +/- 1.0 mmol/l; P < 0.05). Twenty-four-hour glycemia decreased in both groups after dieting, but the MUFA group had a greater decrease than the CHO group (P < 0.05, analysis of variance [ANOVA]). Although decreases in fasting glycemia were maintained in both groups after refeeding, postprandial glycemia deteriorated after refeeding with the CHO- but not the MUFA-enriched formula (P < 0.05). After dieting and refeeding, fasting C-peptide increased 204 +/- 47 pmol/l in the MUFA group, but the CHO group remained at prediet levels (P < 0.05). Twenty-four-hour C-peptide levels were similar between groups after dieting and refeeding, despite the lower glycemia and CHO content of the MUFA formula. However, when equal amounts of CHO were consumed during the OGTT, the MUFA group had significantly higher C-peptide levels after both dieting and refeeding (P < 0.05). Fasting, 24-h, and OGTT insulin levels were similar between groups throughout the study. These results indicate that macronutrient composition is an important determinant of the glycemic response to weight-loss therapy in obese NIDDM patients. Based on the C-peptide response during the OGTT, increased CHO-induced insulin secretion is one possible mechanism by which this occurs.

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Fatty Acids, Monounsaturated; Female; Glucagon; Humans; Insulin; Male; Middle Aged; Obesity; Time Factors; Triglycerides; Weight Loss

Most obese patients with noninsulin-dependent diabetes mellitus (NIDDM) are initially treated with diet, then with oral hypoglycemic agents, eventually with insulin. However several reports indicate that in these patients insulin therapy has little chance to control glucose metabolism, promotes weight gain and arterial hypertension, and is likely to aggravate insulin resistance. In this randomized, double-blind trial vs. placebo (P) we evaluated in 29 obese NIDDM patients poorly controlled by insulin (daily insulin doses 48.7 +/- 4.0 U/day, HbA1c 10 +/- 0.27%, mean daily blood glucose levels 12.3 +/- 0.3 mmol/L, fasting C-peptide 1.8 +/- 0.2, C-peptide after 1 mg iv glucagon 3.2 +/- 0.3 ng/mL, means +/- SE), the clinical and metabolic effects of benfluorex (B), a lipid-lowering drug able to improve insulin sensitivity. After a 2-3 week run-in period (1 tablet P at dinner and diet 800 cal/day to lose 5% of the initial body weight (BWi), patients received a 1000 kcal/day diet and were randomized to B, 150 mg/ tablet, or P (3 tablets/day); the time limit was set at a 10% decrease of BWi or at 90 days. At the end of run-in there was a significant reduction of BWi (P < 0.001), fasting (P = 0.002) and mean daily blood glucose levels (P < 0.001), triglycerides (P = 0.02), cholesterol (P < 0.001) and daily insulin doses (P < 0.001). At the end of the double-blind trial, weight-loss was greater (P < 0.05), faster (P = 0.018), and more frequent (P < 0.05) with B than with P, and systolic blood pressure (P < 0.05) decreased only with B. Considering only patients with a 10% decrease of BWi (B = 15, P = 10), HbA1c (P < 0.001) decreased only with B, while fasting insulin levels decreased with both B (P < 0.01) and with P (P < 0.05). Insulin sensitivity was evaluated by means of a double infusion test (LDIGIT, insulin 25 mU/Kg/h plus glucose 4 mg/kg/min, lasting 150 min) at the end of run-in and at the end of the double-blind trial; at the end of the double-blind trial steady state blood glucose (SSBG, P < 0.05), free fatty acids (FFA, P < 0.05) and blood beta-hydroxybutyrate (P < 0.05) decreased only with B, while blood glycerol decreased both with both P (P < 0.05) and B (P < 0.06). At the end of the double-blind trial, C-peptide release was unchanged with either P or B. In conclusion, benfluorex potentiates the effects of hypocaloric diet on weight loss and on glycemic control in obese NIDDM patients treated with insulin, and this effect seems to be the result of an

Topics: 3-Hydroxybutyric Acid; Appetite Depressants; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Fenfluramine; Glucose; Glycerol; Humans; Hydroxybutyrates; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Obesity; Placebos

To compare results obtained with metformin versus those obtained with DNA-recombinant insulin in obese patients with NIDDM suffering from secondary failure to sulfonylureas.. We conducted an open, prospective, randomized, and comparative study comprising a total of 60 patients selected and placed in two parallel groups. We had previously confirmed that the subjects had secondary failure to high doses of sulfonylureas. The initial metformin dosage was a single 850 mg tablet, and the dosage was increased to two or three tablets depending on the patient's metabolic changes. The initial dosage of DNA-recombinant insulin was 24 U, subcutaneously administered and divided into two portions: two-thirds at around 8:00 A.M., before breakfast, and the remaining third at 8:00 P.M., before dinner. The dosage was adjusted based on the patient's clinical and metabolic response.. The initial average glucose value for the metformin group was 269.1 +/- 32.2 mg/dl, decreasing by the end of the study to 159.7 +/- 30.5 mg/dl. For the insulin group, these figures went from 270.7 +/- 24.0 mg/dl at the beginning of the study to 134.8 +/- 26.7 mg/dl. This decrease correlates with the reduction in glycosylated hemoglobin from 12.8 to 8.9% for the first group and from 12.3 to 8.2% for the second, as well as with the reduction in triglyceride values from 230.3 to 183.1 mg/dl and from 218.4 to 186.3 mg/dl, respectively. The BMI (27.5-26.4), blood pressure (systolic from 145.7-132.1 mmHg, diastolic from 90.3-84.8 mmHg), and total cholesterol levels (235-202 mg/dl) decreased in only the metformin group.. Metformin is an effective, safe, and well-tolerated treatment that improves metabolic control and favorably modifies secondary clinical alterations due to insulin resistance, such as arterial hypertension, overweight, and hyperlipidemia, in obese patients with NIDDM suffering from secondary failure to sulfonylureas.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Lipids; Male; Metformin; Middle Aged; Obesity; Recombinant Proteins; Regression Analysis; Sulfonylurea Compounds; Treatment Failure; Triglycerides

To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas.. Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity.. FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized ( < 6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity.. NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Glucose; Glycated Hemoglobin; Humans; Insulin, Isophane; Liver; Male; Middle Aged; Obesity; Reference Values; Time Factors; Triglycerides

12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.

Topics: Age of Onset; Aged; Blood Glucose; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Liver; Middle Aged; Obesity; Reference Values; Triglycerides; Tritium; Twins, Monozygotic

Short-term administration of physiological amounts of C-peptide to patients with insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in these patients as well as augment whole body glucose utilization. It could also be shown that C-peptide administration increases blood flow, oxygen uptake and capillary diffusion capacity of exercising forearm muscle in IDDM patients, probably by increasing capillary recruitment in the working muscle. Studies under in vitro conditions have shown that C-peptide stimulates glucose transport in skeletal muscle with its maximal effect within the physiological concentration range. The findings in a clinical study in which IDDM patients were given C-peptide and insulin or insulin alone for 4 weeks in a double-blind randomized study design, indicate that C-peptide improves renal function by reducing urinary albumin excretion and glomerular filtration, decreases blood retinal barrier leakage and improves metabolic control. Preliminary findings suggest that C-peptide administration on a short-term basis (3h) may ameliorate autonomic neuropathy by restoring to near normal the heart rate variability in response to expiration and inspiration. Insight into a possible mechanism of action of C-peptide is provided by the finding that C-peptide stimulates Na+K(+)-ATPase activity in renal tubular segments. In conclusion, the present results suggest that, contrary to the prevailing view, C-peptide possesses important physiological effects.

Topics: Animals; Awards and Prizes; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Double-Blind Method; Europe; Glucose; History, 20th Century; Humans; Insulin; Kidney; Muscles; Randomized Controlled Trials as Topic; Regional Blood Flow; Societies, Medical; Sweden

To determine whether previously reported abnormalities in fibrinolytic activity and plasma lipoprotein (a) levels could reflect obesity rather than diabetes per se, plasma concentrations of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and lipoprotein (a) (Lp (a)) were investigated in sixty-four type 2 diabetic patients (56.1 +/- 9.5 years; body mass index, 24.6 +/- 3.3 kg/m2) and thirty-two control subjects (57.9 +/- 8.9 years; body mass index, 24.6 +/- 3.4 kg/m2). Both the plasma t-PA and PAI-1 antigen levels were similar between the diabetic group (10.6 +/- 3.8 ng/ml; 27.7 +/- 11.6 ng/ml) and the control group (12.2 +/- 3.5 ng/ml; 27.7 +/- 9.6 ng/ml). The PAI-1 levels were evenly distributed from 5.93 to 52.7 ng/ml in diabetic patients. The difference of Lp (a) levels between the two groups was negligible (the diabetic group, median 11 mg/dl (range 0-72 mg/dl); the control group, median 13 mg/dl (range 0-55 mg/dl)). Significant correlations between PAI-1 levels and body mass index (BMI) were observed in both groups. In the diabetic group, PAI-1 levels also correlated with fasting C-peptide levels (r = 0.54, P < 0.01) and serum triglyceride levels (r = 0.28, P < 0.05). However, we could not find a significant association between either t-PA or PAI-1 levels and Lp (a) levels in the diabetic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinolysis; Glycated Hemoglobin; Humans; Hypertension; Korea; Lipids; Lipoprotein(a); Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNA(LEU(UUR)) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Base Sequence; C-Peptide; Child; Diabetes Mellitus; DNA Primers; DNA, Mitochondrial; Female; Humans; Islets of Langerhans; Male; MELAS Syndrome; Middle Aged; Mitochondria; Molecular Sequence Data; Pedigree; Point Mutation; Polymerase Chain Reaction; Reference Values; RNA, Transfer, Leu

We have examined the effects of two types of insulin therapy (continuous i.v. infusion (group A: 1.25 u. h-1) and direct i.v. bolus administration of 10 u. every 2 h (group B: 10 u./2 h)) on the metabolic and endocrine responses to surgery in 60 adult diabetic patients undergoing general anaesthesia for elective procedures. Blood glucose concentrations were measured every 15 min from just before induction of anaesthesia until 2 h after surgery. Plasma ketone bodies, lactate, pyruvate, insulin, C-peptide and counter-regulatory hormone concentrations were measured also. Blood glucose concentrations were comparable in both groups, except at 60 min, because of fluctuating blood glucose concentrations in group B. In each group, one patient became hyperglycaemic. One case of hypoglycaemia occurred in group B. There were no statistically significant differences for the other data except for C-peptide. We conclude that, during the operative period, the administration of a direct i.v. bolus of insulin 10 u. every 2 h is a simple and effective method to control blood glucose concentrations; the method can be used when an insulin infusion pump is not available.

Topics: Adult; Aged; Anesthesia, General; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Insulin; Intraoperative Period; Male; Middle Aged; Prospective Studies; Surgical Procedures, Operative; Time Factors

The metabolic effects of a 3-week dietary supplement of a fish oil concentrate was examined in mildly obese, normotriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents (n = 20). Patients were randomized into two groups, receiving 15 ml per day of fish oil (Martens Oil, Norway) containing 3.1 g of omega-3 fatty acids (FA) (n = 10) or placebo (n = 10). Whereas fish oil led to the expected increase in the ratio of omega-3 to omega-6 FA in serum phospholipids, reflecting the increase in omega-3 FA intake, it did not alter fasting or mixed meal stimulated blood glucose, plasma insulin, and C-peptide concentrations. No changes in insulin action were noted, estimated by the metabolic clearance rates of glucose at plasma insulin levels of approximately 100 microU/ml and 1,400 microU/ml during a hyperinsulinemic, isoglycemic clamp; no changes were seen in insulin binding to erythrocytes. We conclude that during short-term administration, no adverse effects of low dose fish oil on glucose homeostasis were found in mildly obese NIDDM patients treated with oral hypoglycemic agents.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Fish Oils; Glyburide; Humans; Insulin; Kinetics; Male; Middle Aged; Obesity; Triglycerides

The Early Treatment Diabetic Retinopathy Study (ETDRS), conducted at 22 clinical centers during the period 1980 to 1989, collected baseline data on C-peptide levels after ingestion of Sustacal in 582 patients with diabetes mellitus, prior to enrollment in the trial. Data on several clinical factors associated with diabetes were also collected from all 3711 enrolled patients. C-peptide data were used to develop sets of clinical criteria for the classification of ETDRS patients and to compare and contrast definitions of type of diabetes used in previous studies. The distribution of C-peptide levels was strikingly bimodal, suggesting a division of study participants into two groups--those with levels at 80 pmol/L or less and those with more than 80 pmol/L of C-peptide after Sustacal ingestion. Constellations of clinical characteristics that could serve as proxies for C-peptide level were ascertained. The result was two sets of clinically developed definitions for type of diabetes in the ETDRS. According to the more restrictive set of definitions, three groups were identified, compared to two groups using the "broad" set of definitions. Discriminant analysis was also used to classify ETDRS patients, yielding similar results. A comparison of definitions of type of diabetes used in the ETDRS and in previous studies revealed that even in the absence of C-peptide data, clinically derived definitions provided good discrimination between type I and type II diabetes.

Topics: Adult; Aspirin; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Diabetic Retinopathy; Discriminant Analysis; Female; Humans; Light Coagulation; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

To examine the effect of prior meal ingestion on the glucose, insulin, and C-peptide response to a 50-g glucose challenge test in the third trimester of pregnancy.. Ten pregnant women with gestational diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age and weight underwent a 50-g glucose challenge test on three occasions within a 2-wk period, in random order. On one occasion the test was administered in the fasting state (fasting glucose challenge test), on a second occasion the test was administered 1 h after ingestion of a standard mixed meal (1-h postprandial study), and on a third occasion the test was administered 2 h after ingestion of a standard mixed meal (2-h postprandial study).. In the control subjects, the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects, insulin and C-peptide levels were higher at the time of ingestion of the 50 g of glucose, but the early (1 h) insulin secretory response was less than in the fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1 subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3 +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the control subjects, the insulin secretory response to 50 g of oral glucose was greater in the two postprandial studies than in the fasting study.. We have reached the following conclusions. 1) In nondiabetic gravidas, plasma glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher if administered in the fasting state compared with the postprandial state. 2) During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose disposal after successive glucose load administrations, occurs and appears to be caused by mechanisms other than enhanced insulin secretion with successive glucose loads. 3) The effect of the prandial state on plasma glucose response to the 50-g glucose challenge test used to screen for gestational diabetes mellitus may be of sufficient magnitude to significantly alter the operating characteristics, i.e., sensitivity and specificity, of this test.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes, Gestational; Eating; Female; Glucose Tolerance Test; Humans; Inulin; Obesity; Pregnancy; Pregnancy Trimester, Third; Reference Values

Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Middle Aged; Obesity

The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These positive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile < 10 mmol.l-1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile > 10 mmol.l-1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day). Metformin was well tolerated by all diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon; Glycated Hemoglobin; Homeostasis; Humans; Islets of Langerhans; Lipids; Male; Metformin; Middle Aged; Obesity; Prospective Studies; Risk Factors; Single-Blind Method

To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk.. The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2).. Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018).. Benfluorex increases insulin sensitivity in obese type II diabetic patients.

Topics: Apolipoprotein A-I; Apolipoproteins B; Appetite Depressants; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Middle Aged; Multivariate Analysis; Obesity; Placebos; Triglycerides

Altogether twenty-six elderly subjects (aged 65-74 years) with persistent impaired glucose tolerance (World Health Organization (1985) criteria) identified in a population-based study, were randomly treated either with chromium-rich yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n 13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11 (SE 0.02) micrograms/d). No significant change was observed in the oral glucose tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3 (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE 0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v. 4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v. 6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein A1 and B levels remained unchanged, and no improvement was seen in serum total cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4) v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein-cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1) v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4) v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for the placebo group). The present results indicate that Cr supplementation does not improve glucose tolerance or serum lipid levels in elderly subjects with stable impaired glucose tolerance.

Topics: Aged; Blood Glucose; Body Mass Index; C-Peptide; Chromium; Diabetes Mellitus; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Lipids; Male; Weight Loss

To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.. A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.. Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.. The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Metformin; Middle Aged; Obesity

Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin-only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone.

Topics: Adult; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glyburide; Glycated Hemoglobin; Humans; Insulin; Lipoproteins; Obesity; Triglycerides

Our objective was to determine whether 1) hydrogenated starch hydrolysates (HSHs), bulking/sweetening agents used in hard candies, produce a diminished postmeal glycemic response relative to glucose in individuals with and without diabetes and 2) any diminished glycemia is secondary to altered carbohydrate absorption. This study followed a randomized double-blind crossover design and was performed in 12 individuals with diabetes (6 non-insulin dependent, 6 insulin dependent) and 6 nondiabetic individuals. Each group consisted of 3 men and 3 women, none with known neuropathy. After an overnight fast, each subject was challenged with 50 g of glucose, HSH 5875 (7% sorbitol/60% maltitol), and HSH 6075 (14% sorbitol/78% hydrogenated maltooligosaccharides)/1.73 m2 of body surface area in random order on 3 successive days. Individuals with diabetes were maintained on continuous subcutaneous insulin infusion throughout the study to achieve prechallenge glucose levels between 4.5 and 6.7 mM. For all groups, the order of plasma glucose responses over 5 h postchallenge was glucose greater than HSH 6075 greater than HSH 5875, P less than 0.001 (glucose vs. HSH). Pooled data for all groups for areas under the curve confirmed that HSH 6075 resulted in greater glycemia than HSH 5875 (P less than 0.05). This was reflected in the order of C-peptide responses seen in the nondiabetic and non-insulin-dependent groups (glucose greater than HSH 6075 greater than HSH 5875, P less than 0.001). Breath H2 after glucose was low, whereas HSH 5875 greater than HSH 6075 (P = 0.003). Gastric distress was noticed with all products.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Female; Glucose; Humans; Insulin; Insulin Infusion Systems; Male; Middle Aged; Random Allocation; Reference Values; Sugar Alcohols

Hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) stimulates peripheral glucose uptake, which tends to compensate for impaired insulin-mediated glucose uptake. The metabolic fate of glucose and suppression of fat oxidation may differ, however, when glucose uptake is stimulated primarily by insulin or hyperglycemia. To address this issue, three hyperinsulinemic glucose-clamp studies were performed in combination with indirect calorimetry in seven nonobese subjects with NIDDM. In the first two experiments, when glucose uptake was matched at approximately 8 mg.kg-1 fat-free mass (FFM).min-1 with primarily hyperinsulinemia (1350 +/- 445 pM) or hyperglycemia (20.8 +/- 1.8 mM), identical rates of glucose oxidation (3.21 +/- 0.29 and 3.10 +/- 0.23 mg.kg-1 FFM.min-1, NS) and nonoxidative glucose metabolism (5.19 +/- 0.75 and 5.46 +/- 0.61 mg.kg-1 FFM.min-1, NS) were achieved. When glucose uptake was increased further to 11.11 +/- 0.36 mg.kg-1 FFM.min-1 with less insulin (625 +/- 70 pM) and hyperglycemia, glucose oxidation (3.85 +/- 0.26 mg.kg-1 FFM.min-1) and nonoxidative glucose metabolism (7.26 +/- 0.51 mg.kg-1 FFM.min-1) rose significantly (both P less than 0.05 from matched studies at lower rates of glucose uptake). During all glucose-clamp studies, free fatty acids were comparably suppressed by 40-46% (all P less than 0.005 vs. basal values), whereas fat oxidation was suppressed by 70-80% (all P less than 0.005 vs. basal values). A strong negative correlation was observed between rates of glucose and fat oxidation (r = -0.88, P less than 0.001) when all studies were combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Clamp Technique; Humans; Hyperglycemia; Hyperinsulinism; Insulin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxidation-Reduction

We studied 12 subjects with diabetes to determine how well the glycemic index (GI) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted GI in every individual. The observed mean +/- SD GI values of the meals were significantly different from each other (bread 100 +/- 7, rice 75 +/- 9, spaghetti 54 +/- 9), with no significant difference in response between subjects. It is concluded that individuals share common mean GI values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected GI difference, the GI can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.

Topics: Adult; Aged; Blood Glucose; Bread; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Energy Intake; Fasting; Female; Flour; Humans; Male; Middle Aged; Oryza; Random Allocation

Forty-two obese subjects with non-insulin-dependent diabetes mellitus had their plasma insulin, C peptide, and glucose levels measured after an overnight fast and in response to a 75-g oral glucose loading. Subjects were then prospectively followed up with dietary treatment, and the same measurements were repeated at 1 year. Although insulin values tended to be lower with greater fasting hyperglycemia at baseline, no correlation was observed among three parameters. However, near-normalization of glycemia (measured as the level of hemoglobin A1) was associated with significantly higher fasting and stimulated plasma insulin concentrations. Sixteen subjects were matched to each other for equivalent baseline hyperglycemia (by glycosylated hemoglobin) and divided into group 1 (normalization of the hemoglobin A1 value to 7.0% +/- 0.3% [mean +/- SE]) and group 2 (persistent hyperglycemia) (hemoglobin A1 value, 10.7% +/- 0.7% [mean +/- SE]). Before dietary therapy, the plasma insulin concentrations were twofold to threefold higher in group 1, and despite similar degrees of weight loss, group 2 failed to demonstrate improved glycemia. We concluded that the outcome of diet therapy for non-insulin-dependent diabetes mellitus is dependent on the duration of diabetes and endogenous insulin secretory reserve. There is a subgroup of patients with non-insulin-dependent diabetes mellitus in whom delayed dietary intervention may have a beneficial effect.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Time Factors

Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n = 31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n = 68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20 +/- 3 pmol/l to a peak of 68 +/- 5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27 +/- 3 pmol/l to a higher peak value of 104 +/- 6 pmol/l at 30 min (p less than 0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30-90 min (p less than 0.01-0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22 +/- 4 pmol/l to a peak of 93 +/- 6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25 +/- 2 pmol/l to a higher peak of 133 +/- 7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p less than 0.001), 60 min (p less than 0.01) and from 210-240 min (p less than 0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Eating; Female; Gastric Inhibitory Polypeptide; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity; Random Allocation; Reference Values

Insulin requirements, C-peptide levels, and serum lipids have been assessed in 12 obese, insulin-requiring (greater than 60 U/day) patients with type II diabetes mellitus, in a randomized crossover fashion with two treatment regimens: NPH alone and combined NPH and tolazamide, over a period of 3 months each, with maintenance of weight and glycemic control (HgA1, 2hpp and mean 24h glucose profile) at comparable levels. Serum cholesterol improved in both groups compared to their respective baseline values (p less than 0.05). In addition, serum triglyceride was lower (p less than 0.05) in the combined therapy as compared with NPH alone therapy. Insulin requirements were decreased by 23% (p less than 0.002) in the combined therapy group, without significant change in weight, glycemic control, or C-peptide levels. However, C-peptide increments in the combined therapy group were significantly higher than the baseline by 70% (p less than 0.02). NPH plus tolazamide therapy as compared with NPH alone lowers insulin requirement in obese, type II diabetic women without significant alteration in glycemic control, possibly by an increased tissue sensitivity to insulin, and decreases serum triglyceride levels.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Random Allocation; Tolazamide; Triglycerides

An insulin suppression test performed in random order with either biosynthetic human insulin or purified pork insulin was used to compare biological activity of these two insulins in obese patients suffering from varying degrees of glucose intolerance. Blood glucose curve, steady-state blood glucose levels, insulin sensitivity indices and steady-state plasma insulin levels were identical during the two sets of tests. Furthermore endogenous insulin and glucagon secretion were similarly suppressed. The insulin suppression test is a simple and rapid procedure to compare the biological activity of fast-acting insulins. Our results confirm the insulin-resistance in obesity and clearly show that biosynthetic human and porcine insulins have similar biological potency.

Topics: Adult; Aged; Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Pork; Male; Middle Aged; Obesity; Recombinant Proteins; Somatostatin; Swine

Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a standardized diet and were treated either with Bay m 1099, b.d. (100 mg before breakfast and dinner) or placebo for 3 days, according to a double-blind cross-over design. The postprandial blood glucose level was significantly lower during Bay m 1099 treatment compared to placebo after breakfast and dinner (AUC after breakfast p less than 0.001). The reduced postprandial hyperglycaemia was associated with a decrease in meal stimulated serum insulin and C-peptide levels. Thus, Bay m 1099 may be a useful addition in the treatment of Type II diabetic patients.

Topics: 1-Deoxynojirimycin; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Eating; Female; Glucosamine; Glycoside Hydrolase Inhibitors; Humans; Imino Pyranoses; Insulin; Male; Middle Aged; Obesity; Pancreatic Hormones

Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.

Topics: Ampicillin; Bacterial Infections; Blood Glucose; C-Peptide; Diabetes Complications; Diabetes Mellitus; Drug Therapy, Combination; Floxacillin; Glucagon; Humans; Middle Aged; Penicillanic Acid; Sulbactam; Time Factors

As part of a multicenter trial, 70 individuals with insulin-dependent diabetes were randomized to either conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion (CSII). In order to standardize patient selection in the six participating centers, one of the eligibility criteria was the demonstration that each patient had no residual endogenous insulin secretion as assessed by plasma C-peptide determinations. The patients were of average (+/- SEM) age of 33.0 +/- 1.6 yr, had had diabetes for a mean (+/- SEM) duration of 17.4 +/- 1.1 yr, and had both fasting and postglucagon stimulation C-peptide values of less than 0.1 pmol/ml, consistent with clinically insignificant endogenous insulin secretion. There was no change in C-peptide response at 4 or 8 mo compared with baseline values, whether or not the patient's glucose control remained unchanged (CIT group) or significantly improved to near-normoglycemia (CSII group). In a subgroup of 34 patients at three centers, the 24-h mean glucose concentration was significantly lower in the CSII group compared with the CIT group at 4 mo (126 +/- 10 versus 176 +/- 14 mg/dl) and at 8 mo (121 +/- 5 versus 183 +/- 15 mg/dl) (P less than 0.005). Although the 24-h mean serum free immunoreactive insulin levels were shown to be no different at baseline (27.4 +/- 3.8 versus 26.2 +/- 3.1 microU/ml) or after 4 mo (22.5 +/- 3.2 versus 25.6 +/- 3.2) or 8 mo (26.5 +/- 3.4 versus 28.8 +/- 3.4) of CIT or CSII therapy, respectively, the mean increase of free insulin concentrations in relation to the main meals was greater in the CSII group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diagnosis-Related Groups; Humans; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Middle Aged

In 16 non-diabetic and 16 diabetic patients prenalterol, dobutamine and dopamine infusions (5 micrograms/kg/min for 30 min) were given. The haemodynamic and metabolic changes were similar in diabetics and non-diabetics. Prenalterol has the most pronounced haemodynamic effect on heart rate (increase 25-47%) and the heart rate-blood pressure-product (increase 54-81%). The metabolic effects were moderate. The slight lipolytic effect of prenalterol documented its functional selectivity for beta 1-adrenoceptors.

Topics: Adrenergic beta-Agonists; Adult; Aged; Blood Pressure; C-Peptide; Diabetes Mellitus; Dobutamine; Dopamine; Heart Rate; Hemodynamics; Humans; Infusions, Parenteral; Lipolysis; Middle Aged; Practolol; Prenalterol

An assessment of the metabolic effect of dietary carbohydrate on daily insulin secretion, reflected by the 24-h urine output of C-peptide, has been made. Urinary C-peptide excretion increased when the carbohydrate intake of 6 normal subjects was increased from 200 to 400 g. A high-fibre diet rich in beans and lentils caused a significant fall in urine C-peptide and a lowering of blood glucose values in both normal and diabetic subjects. This confirms the insulin-sparing effect of leguminous foods. An increase of dietary fibre to 50 g mainly as cereal fibre did not significantly alter urine C-peptide excretion in normal subjects. Urinary C-peptide estimations could be useful for assessing the effect of different diets on daily insulin secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet; Dietary Carbohydrates; Dietary Fiber; Dose-Response Relationship, Drug; Edible Grain; Fabaceae; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Peptides; Plants, Medicinal

In a randomized cross-over study, 24 type II diabetics were given at first 50 g palatinite and later 50 g glucose or vice versa in the morning before food intake. After administration of glucose there was a definite rise in blood-glucose, serum-insulin and C-peptide concentrations. After palatinite the rise of blood-glucose as well as serum-insulin and C-peptide was significantly less. Subjective side-effects were noted only after a single high dose of palatinite. Nonetheless, palatinite appears to be suitable as a sugar substitute in a diabetic diet, since in comparison with glucose there are no significant changes in blood-sugar levels and no additional insulin consumption is induced. Furthermore, because of its low energetic utilization it has an advantage over other sugar substitutes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus; Disaccharides; Fatty Acids, Nonesterified; Female; Humans; Insulin; Male; Middle Aged; Random Allocation; Sugar Alcohols; Sweetening Agents

Within 24h of diagnosis, 15 consecutive Type 1 (insulin-dependent) diabetic patients were allocated at random to one of two treatment groups: group A (n = 9, mean age: 28 years, range: 17-35 years) was treated conventionally with one or two daily doses of insulin; group B (n = 6, mean age: 27 years, range: 21-37 years) was treated with nine daily injections of fast-acting insulin for ten days and there-after conventionally as for group A. The mean diurnal blood glucose concentration during the initial ten days of insulin treatment was 11.7 +/- 0.5 mmol/l (mean +/- SEM) in group A and 6.4 +/- 0.3 mmol/l in group B (p less than 0.01). Pancreatic B cell function was evaluated 1, 7, 14, 90, and 180 days after the start of insulin treatment from the C-peptide response to a standard meal. At one and seven days after diagnosis, no difference was found in B cell function between the two groups. After 14 days, the amount of C-peptide secreted during the test meal was 18.0 +/- 2.6 nmol (mean +/- SEM) in group A compared with 29.0 +/- 3.6 nmol in group B (p less than 0.05). After 90 and 180 days, no difference was demonstrated in B cell function. The maximal B cell function observed was similar in the two groups, but occurred earlier in group B (at 14 days) than in group A (at 90 days) (p less than 0.05). This study indicates that strict initial glycaemic control may lead to an earlier improvement in B cell function, but that this improvement is of short duration.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Male

In a double-blind cross-over trial we compared the effects of placebo and propranolol on iv tolbutamide and oral glipizide-stimulated insulin secretion in 10 non-insulin dependent diabetics. The patients were randomly allocated for 2 weeks treatment with placebo and propranolol 80 mg twice daily. At the end of each period an iv tolbutamide test and an oral glipizide-glucose-test were performed. Tolbutamide-stimulated insulin secretion was not affected by propranolol. There was no change in blood glucose levels during the iv tolbutamide test (IVTT), which excluded an effect of blood glucose on insulin secretion. During the oral glipizide-glucose challenge propranolol decreased blood glucose at 60 min (P less than 0.01) and increased C-peptide at 0 min (P less than 0.01) and 30 min (P less than 0.05) compared with placebo. In contrast to earlier results obtained in animals and healthy subjects propranolol does not inhibit insulin- or C-peptide responses to sulphonylurea in patients with non-insulin dependent diabetes mellitus.

Topics: Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus; Double-Blind Method; Female; Glipizide; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Propranolol; Random Allocation; Sulfonylurea Compounds; Tolbutamide

The therapeutic effect of tolbutamide (1.5 g daily) in a random sample of patients with non-insulin dependent diabetes mellitus (NIDDM), was studied in a controlled, double-blind cross-over trial of 13 women and 6 men, aged 40-65 years and of 85-155% ideal body weight. The trial comprised C-peptide determinations during a standard carbohydrate rich meal followed by four periods of 3 months in which alternating tolbutamide and placebo were given. From the beginning to the end of the treatment periods fasting blood glucose was reduced from 11.9 +/- 1.1 (mean +/- SEM) to 10.0 +/- 0.8 mmol/l (P less than 0.025), glycohaemoglobin from 12.8% +/- 0.7 to 11.3% +/- 0.5 (P less than 0.02) with a close correlation between fasting blood glucose and glycohaemoglobin (r = 0.87, P less than 0.001). The observations during the first 3 months of study was not included in the calculations. Fasting C-peptide and fasting insulin concentrations were not significantly altered by tolbutamide treatment. The effect of tolbutamide was inversely correlated to the C-peptide response to the standard test meal at the start of the trial (r = 0.76, P less than 0.01), so that patients with the most pronounced beta-cell failure had the greatest therapeutical effect. The beta-cell response to the test meal could not identify patients, whose fasting blood glucose would be normalized by tolbutamide treatment.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Random Allocation; Tolbutamide

The present study was undertaken to reevaluate the influence of somatostatin on platelet function in insulin-dependent diabetics and in normal subjects. In in vivo studies, nine insulin-requiring diabetics were infused with cyclic somatostatin (250 microgram/hour) for 120 minutes or with saline, in randomized order. This dose of somatostatin, sufficient to depress the basal concentrations of plasma glucose, glucagon and C-peptide, resulted in no significant change of platelet aggregation response to either ADP or collagen. By contrast, a progressive and significant reduction of platelet aggregation response to ADP was found during saline infusion. A similar pattern of response was seen in normal subjects. In all diabetics, but not in normals, somatostatin induced the appearance of circulating platelet aggregates. In in vitro studies, somatostatin augmented the aggregation response to epinephrine in both normals and diabetics. In conclusion, somatostatin counteracts the decrease of platelet aggregation response to ADP seen in saline studies, induces the appearance of platelet aggregates in diabetics and potentiates the aggregation response to epinephrine (in vitro) in both normals and diabetics. These actions of somatostatin suggest some aggregating capacity of the peptide in man.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Male; Middle Aged; Platelet Aggregation; Somatostatin

The purpose of the study was to investigate whether the potency of effect on the beta cell differs with type of sulfonylurea (SU) and with degree of severity of diabetes. 12 maturity onset diabetics were classed according to fasting blood glucose (FBG) in three groups of 4 patients each. Each patient served as his own control. Glibenclamide, Gliquidone, Glusoxepide and placebo were administered in random order with degree dosage adjusted according to degree of severity of diabetes. All patients were given a standardized diet with 150 g carbohydrates per day. Fullday profiles of blood glucose, insulin, C-peptide and sulfonylurea level in serum were made on the third day under each preparation. Results showed that with proper nutrition and sufficient weight reduction, patients in group I (FBG 80--130 mg/dl) needed no oral medication and in fact showed a tendency towards hypoglycaemic episodes under oral therapy. In group II (FBG 130--200 mg/dl) the effect of nutrients on beta cell secretion appeared to be both enhanced and accelerated by SU administration. Satisfactory metabolic control was achieved with SU, but not with placebo. This group seems to represent the type of patient most likely to benefit from SU therapy. In spite of high dosage levels, satisfactory control was not achieved with SU in any patient in group III (FBG greater than 200 mg/dl). Depending on individual factors such as ketosis-proneness, vascular complications, age and psycho-social aspects, insulin administration should be considered for these patients. There were not differences between the individual SU preparations in the parameters studied. There was insufficient evidence for a pharmacokinetic differential diagnosis.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Glyburide; Humans; Placebos; Sulfonylurea Compounds

A high-carbohydrate-(HC)-modified fat diet was compared with a standard low-carbohydrate (LC) diabetic diet in 11 insulin-dependent diabetics. Basal and preprandial plasma glucose concentrations were appreciably lower when the patients received the HC diet derived chiefly from readily available cereal and vegetable sources (mean (+/- SE of mean) basal concentrations 6.7 +/- 1.2 mmol/l (121 +/- 22 mg/100 ml) with the LC diet and 4.3 +/- 0.7 mmol/l (77 +/- 13 mg/100 ml) with the HC diet; mean preprandial concentrations 11.1 +/- 1.2 mmol/l (200 +/- 22 mg/100 ml) LC diet and 8.9 +/- 1.3 mmol/l (160 +/- 23 mg/100 ml) HC diet). total and low-density lipoprotein cholesterol concentrations were lower when patients took the HC diet (mean 4.4 +/- 0.2 and 2.4 +/- 0.2 mmol/l (189 +/- 8 and 124 +/- 8 mg/100 ml) respectively), and the ratio of high-density lipoprotein cholesterol to total cholesterol tended to rise. The average percentage of glycosylated haemoglobin did not differ between the two diets. Thus several measures of carbohydrate and lipid metabolism appear to be more satisfactory when patients receive a HC diet, which is an acceptable alternative to that still recommended to most insulin-requiring patients.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diet, Diabetic; Dietary Carbohydrates; Female; Humans; Insulin; Male; Middle Aged; Triglycerides

Factitious hypoglycemia is a factitious disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), referring to intentionally covertly induced hypoglycemia, with potentially severe consequences. Knowledge of factitious hypoglycemia relies on case reports, and evidence-based information and guidelines are lacking. Diagnosing factitious hypoglycemia in insulin-treated diabetic persons is therefore challenging and often requires a long and costly process. Moreover, the typical metrics proposed to differentiate insulin-induced factitious hypoglycemia from insulinoma (i.e., high insulin and low C-peptide versus high insulin and high C-peptide, respectively) are not always applicable, depending on whether the insulin quantification method can detect the insulin analog. When factitious hypoglycemia is suspected, an emerging trend from recent publications advocates a combination of two insulin quantification methods with different cross-reactivity for insulin analogs, early on in the diagnostic process.

Topics: C-Peptide; Diabetes Mellitus; Factitious Disorders; Humans; Hypoglycemia; Insulin; Pancreatic Neoplasms

Topics: Animals; C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Endothelial Cells; Humans; Hyperglycemia; Mice; Neovascularization, Pathologic; Retinal Neovascularization

The possible mechanism of increased urinary C-peptide due to neprilysin inhibitors is investigated. Neprilysin inhibition blocks degradation of natriuretic peptides, and elicits a natriuretic and antihypertensive effect. Neprilysin inhibition might similarly block degradation of C-peptides in the kidney and thus increase the urinary C-peptide level.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; C-Peptide; Diabetes Mellitus; Drug Combinations; Heart Failure; Humans; Neprilysin; Tetrazoles; Valsartan

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Predicting the risk of developing DPN is important for clinical decision-making and designing clinical trials.. We retrospectively reviewed the data of 1278 patients with diabetes treated in two central hospitals from 2020 to 2022. The data included medical history, physical examination, and biochemical index test results. After feature selection and data balancing, the cohort was divided into training and internal validation datasets at a 7:3 ratio. Training was made in logistic regression, k-nearest neighbor, decision tree, naive bayes, random forest, and extreme gradient boosting (XGBoost) based on machine learning. The k-fold cross-validation was used for model assessment, and the accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC) were adopted to validate the models' discrimination and clinical practicality. The SHapley Additive exPlanation (SHAP) was used to interpret the best-performing model.. The XGBoost model outperformed other models, which had an accuracy of 0·746, precision of 0·765, recall of 0·711, F1-score of 0·736, and AUC of 0·813. The SHAP results indicated that age, disease duration, glycated hemoglobin, insulin resistance index, 24-h urine protein quantification, and urine protein concentration were risk factors for DPN, while the ratio between 2-h postprandial C-peptide and fasting C-peptide(C2/C0), total cholesterol, activated partial thromboplastin time, and creatinine were protective factors.. The machine learning approach helped established a DPN risk prediction model with good performance. The model identified the factors most closely related to DPN.

Topics: Bayes Theorem; C-Peptide; Diabetes Mellitus; Diabetic Neuropathies; Humans; Machine Learning; Retrospective Studies; Risk Factors

The prevalence of diabetic foot ulcers, a common, more serious chronic diabetes-related complication, is increasing. Vacuum sealing drainage (VSD) constitutes an effective adjunctive treatment for diabetic foot ulcers. Factors, such as poor glycemic control, ischemia, and infection prolong wound healing time, and VSD products are expensive and unaffordable for many patients.. To compare the use of customized VSD and customized VSD in the treatment of diabetic foot ulcer.. This retrospective study included 83 patients with diabetic foot ulcers in customized VSD (n = 44) and VSD (n = 39) groups. Baseline data, efficacy after 14 days, total treatment efficiency, final outcome (28 days after treatment, healing rate), average treatment cost, and hospitalization (days) of the two groups were compared. Factors affecting wound healing were analyzed.. No significant intergroup differences in the baseline data were detected (VSD vs. customized VAD, p > 0.05). Treatment efficacy was higher in the customized VSD group than in the VSD group after 14 days (p < 0.05), although total treatment efficiency in both groups reached 100%. The final outcome in the customized VSD group was better (vs. VSD group, p < 0.05), and the wound healing rate was higher than in the VSD group (66.7% vs. 33.3%). The mean treatment cost and hospital days were greater in the VSD group (vs. customized VSD group; p < 0.05). Factors affecting wound healing include age, Wagner classification, HDL-C, and fasting C-peptide. Younger age, low Wagner classification grade, low HDL-C level, and high fasting C-peptide contribute to higher healing rate, CONCLUSION: Efficacy and final outcome of customized VSD were better than that of VSD; the customized VSD device is simple and convenient to operate, and enables cost-effective treatment.

Topics: C-Peptide; Diabetes Mellitus; Diabetic Foot; Drainage; Humans; Negative-Pressure Wound Therapy; Retrospective Studies; Treatment Outcome

Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.. MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit. The differentiated cells were evaluated by immunocytochemistry staining for Insulin and PDX-1. Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.. Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their higher potency.

Topics: Adipose Tissue; Bone Marrow; Bone Marrow Cells; C-Peptide; Cell Differentiation; Diabetes Mellitus; Glucose; Humans; Insulin; Insulin-Secreting Cells; Mesenchymal Stem Cells

To investigate factors influencing glycemic control in diabetes mellitus complicated by autoimmune pancreatitis.. This retrospective cohort study investigated 33 patients with diabetes mellitus complicated by autoimmune pancreatitis who had received steroid therapy at Toranomon Hospital between January 1, 2011, and December 31, 2020. The course of glycemic control at 12 months after starting steroids was classified into three groups: Improved, Unchanged, or Worsened. Factors affecting these groups were investigated. Furthermore, we created two scores: (1) time of diabetes mellitus onset and baseline body mass index; (2) time of diabetes mellitus onset and baseline C-peptide index. Diabetes mellitus occurring at the same time as autoimmune pancreatitis, body mass index ≥22 kg/m. Ten patients were in the Improved group, 10 were in the Unchanged group, and 13 were in the Worsened group. The baseline body mass index and baseline C-peptide index were lower in the Worsened group than in the Improved group (P < 0.05 each). In addition, the scores were lower in the Worsened group than in the other groups (P < 0.05).. Patients with a lower baseline body mass index and a decreased baseline C-peptide index may experience worse glycemic control on steroid therapy.

Topics: Autoimmune Pancreatitis; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Retrospective Studies; Steroids

Diabetes mellitus (DM) is one of the most common underlying diseases that may aggravates COVID-19. In the present study, we explored islet function, the presence of SARS-CoV-2 and pathological changes in the pancreas of patients with COVID-19. Oral glucose tolerance tests (OGTTs) and the C-peptide release test demonstrated a decrease in glucose-stimulated C-peptide secretory capacity and an increase in HbA1c levels in patients with COVID-19. The prediabetic conditions appeared to be more significant in the severe group than in the moderate group. SARS-CoV-2 receptors (ACE2, CD147, TMPRSS2 and neuropilin-1) were expressed in pancreatic tissue. In addition to SARS-CoV-2 virus spike protein and virus RNA, coronavirus-like particles were present in the autophagolysosomes of pancreatic acinar cells of a patient with COVID-19. Furthermore, the expression and distribution of various proteins in pancreatic islets of patients with COVID-19 were altered. These data suggest that SARS-CoV-2 in the pancreas may directly or indirectly impair islet function.

Topics: C-Peptide; COVID-19; Diabetes Mellitus; Humans; Pancreas; SARS-CoV-2

The role of executive functions (EF) is to maintain particular behaviours in order to achieve intended goals. EF are crucial in management of pre-diabetes, diabetes and obesity which are grievous diseases and can lead to severe complications. The aims of our study were to: assess EF in group of obese subject with carbohydrate disorders, evaluate whether biochemical factors and comorbidities related to metabolic disorders have adverse effect on EF in this group of patients.. The study included 185 obese patients (146 women; 39 men) who were divided on three groups: pre-diabetic, diabetic and control subgroup. Patient underwent Wisconsin Card Sorting Test (WCST) to evaluate EF. Assessed biochemical factors included C-peptide, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c).. Diabetic patients showed the worst WCST scores among the rest of groups. Pre-diabetic individuals did not differ in EF performance from control subgroup. We observed significant correlations between FPG and HbA1c and worse WCST scores in pre-diabetic subgroup. In diabetic patients C-peptide correlated with poorer EF. Depressive symptoms and hypertension significantly correlated with non-perseverative errors in WCST.. The subgroup of diabetic patients were the most obese and had the worst glycemia parameters. They also showed the worst EF in WCST. According to obtained results, hyperglycemia positively correlated with poor EF in pre-diabetes. However, in diabetic subjects cognitive deterioration may results from insulin resistance rather than hyperglycemia. In obese individuals with carbohydrate disorders both hypertension and depressive symptoms significantly contributed to EF dysfunction.

Topics: C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Male; Obesity; Prediabetic State; Prefrontal Cortex

Cushing’s disease (CD) causes diabetes mellitus (DM) through different mechanisms in a significant proportion of patients. Glucose metabolism has rarely been assessed with appropriate testing in CD; we aimed to evaluate hormonal response to a mixed meal tolerance test (MMTT) in CD patients and analyzed the effect of pasireotide (PAS) on glucose homeostasis. To assess gastro-entero-pancreatic hormones response in diabetic (DM+) and non-diabetic (DM−) patients, 26 patients with CD underwent an MMTT. Ten patients were submitted to a second MMTT after two months of PAS 600 µg twice daily. The DM+ group had significantly higher BMI, waist circumference, glycemia, HbA1c, ACTH levels and insulin resistance indexes than DM− (p < 0.05). Moreover, DM+ patients exhibited increased C-peptide (p = 0.004) and glucose area under the curve (AUC) (p = 0.021) during MMTT, with a blunted insulinotropic peptide (GIP) response (p = 0.035). Glucagon levels were similar in both groups, showing a quick rise after meals. No difference in estimated insulin secretion and insulin:glucagon ratio was found. After two months, PAS induced an increase in both fasting glycemia and HbA1c compared to baseline (p < 0.05). However, this glucose trend after meal did not worsen despite the blunted insulin and C-peptide response to MMTT. After PAS treatment, patients exhibited reduced insulin secretion (p = 0.005) and resistance (p = 0.007) indexes. Conversely, glucagon did not change with a consequent impairment of insulin:glucagon ratio (p = 0.009). No significant differences were observed in incretins basal and meal-induced levels. Insulin resistance confirmed its pivotal role in glucocorticoid-induced DM. A blunted GIP response to MMTT in the DM+ group might suggest a potential inhibitory role of hypercortisolism on enteropancreatic axis. As expected, PAS reduced insulin secretion but also induced an improvement in insulin sensitivity as a result of cortisol reduction. No differences in incretin response to MMTT were recorded during PAS therapy. The discrepancy between insulin and glucagon trends while on PAS may be an important pathophysiological mechanism in this iatrogenic DM; hence restoring insulin:glucagon ratio by either enhancing insulin secretion or reducing glucagon tone can be a potential therapeutic target.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Incretins; Insulin; Insulin Resistance; Meals; Pituitary ACTH Hypersecretion; Somatostatin

Type A Insulin resistance syndrome (TAIRS) is an autosomal dominant or recessive genetic disorder caused by insulin dysfunction resulting from insulin receptor (INSR) gene mutation. The main features of TAIRS include hyperinsulinemia, abnormal glucose metabolism, and changes in acanthosis nigricans. We identified, in China, a TAIRS family with a novel heterozygous missense gene mutation type. One patient from the Chinese Han family exhibited signs and symptoms of TAIRS and was presented for evaluation. Whole-exome sequencing revealed a heterozygous mutation. Both the patient proband and his father were identified with insulin receptor exon 19c.3472C>T(p.Arg1158Trp), which resulted in a missense mutation that led to replace by a base in the amino acid codon. We found that the patient proband and his father exhibited high insulin and C-peptide release after glucose stimulation by insulin and C-peptide release tests. At the same time, we also ruled out the possibility of islet βcell tumor through relevant examinations. These findings indicate that the INSR gene mutation may cause pancreatic β cell functional impairment and contribute to the development of diabetes.

Topics: C-Peptide; Diabetes Mellitus; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Mutation, Missense; Receptor, Insulin

This study aimed to identify the clinical factors affecting postoperative residual pancreatic β-cell function, as assessed by the C-peptide index (CPI), and to investigate the association between perioperative CPI and the status of diabetes management after pancreatectomy.. The associations between perioperative CPI and clinical background, including surgical procedures of pancreatectomy, were analyzed in 47 patients who underwent pancreatectomy, and were assessed for pre-and postoperative CPI. The association between perioperative CPI and glycemic control after pancreatectomy was investigated.. The low postoperative CPI group (CPI <0.7) had longer duration of diabetes (17.5 ± 14.5 vs 5.5 ± 11.0 years, P = 0.004), a higher percentage of sulfonylurea users (41.7 vs 8.7%, P = 0.003) and a greater number of drug categories used for diabetes treatment (1.9 ± 1.1 vs 0.8 ± 0.8, P <0.001) than did the high postoperative CPI group. Postoperative CPI was higher (1.4 ± 1.2 vs 0.7 ± 0.6, P = 0.039) in patients with low glycosylated hemoglobin (<7.0%) at 6 months after pancreatectomy; preoperative (2.0 ± 1.5 vs 0.7 ± 0.5, P = 0.012) and postoperative CPI (2.5 ± 1.4 vs 1.4 ± 1.1, P = 0.020) were higher in non-insulin users than in insulin users at 6 months after surgery.. The duration of diabetes and preoperative diabetes treatment were associated with residual pancreatic β-cell function after pancreatectomy. Furthermore, perioperative β-cell function as assessed by CPI was associated with diabetes management status after pancreatectomy.

Topics: C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; Humans; Pancreatectomy; Postoperative Complications; Retrospective Studies

We aimed to identify clinical characteristics and biochemical parameters at presentation in newly diagnosed children and adolescents with Fibrocalculous pancreatic diabetes (FCPD) and compare them with Type 1 Diabetes (T1D) children.. A retrospective chart review yielded 226 patients (below 18 years) who presented and fulfilled diagnostic criteria of diabetes mellitus. Classification of diabetes was based on American Diabetes Association (ADA), World Health Organization (WHO), International Society for Paediatric and Adolescent Diabetes (ISPAD), and Mohan's criteria and all patients underwent abdominal X-ray.. A total of 31 (13.7%) patients fulfilled criteria of FCPD and 63 (27.9%) of autoantibody positive T1D. When comparing FCPD with T1D at presentation, FCPD patients were older, 14.23 years vs 11.32 years. Fewer FCPD patients presented with Diabetic Ketoacidosis (3.2% vs 34.9%), osmotic symptoms (54.8% vs 93.7%) with significantly longer median duration of symptoms (4.0 vs 1.0 months) and had more abdominal pain (58.06% vs 6.3%) & diarrhoea (38.71% vs 1.6%) as compared to patients with T1D". FCPD patients had higher c-peptide levels (median-0.85 vs 0.61) and required higher mean dose of insulin compared to T1D (1.16 U/kg vs 1.01 U/kg). At presentation fasting plasma glucose was significantly higher in T1D than FCPD, but no difference was noted in post prandial glucose and HbA1c.. There is a significant difference in clinical characteristics and biochemical parameters at presentation between FCPD and T1D patients with a longer symptom duration but insidious course in the former. To the best of our knowledge, this is the first study to report suitable cut-offs for age, c-peptide, duration of symptoms and insulin dose requirement which could be helpful for differentiating FCPD from T1DM patients.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; India; Insulin; Pancreatitis; Retrospective Studies

The presence of technological devices in our lives has increased exposure to environmental electromagnetic fields. As a result of this, especially Cancer and Diabetes are increasing.Rats were divided into 3 groups with 12 rats in each group. The 1st experimental group (n = 12) was exposed to a 50 Hz ELF magnetic field of 0.4 mT for 6 hours a day for 5 days, the 2nd experimental group (n = 12) was exposed for 10 days, and the control group (n = 12) was never exposed to a magnetic field. After completing the applications, blood collection from the rats was performed under appropriate conditions, measurements were made in the laboratory, and statistical analysis was performed between the groups. There was no significant difference between the groups in the results of transaminases and lipid profiles and C-Peptide. There was no significant difference in insulin, urea, creatinine, Na, K, Ca, and uric acid parameters between the groups. However, there was a significant increase in glucose, HbA1c, and Hba1 IFCC values between the control group and the experimental groups (p < .001). There was a significant increase in the level of Fetuin-A between the control group and the experimental groups (p < .05). There was an increase in the Fetuin-A, Glucose, HbA1c, and Hba1c IFCC values in both of the experimental groups compared to the control group. We believe that an increase in these values may cause Type 3 diabetes.

Topics: alpha-2-HS-Glycoprotein; Animals; C-Peptide; Creatinine; Diabetes Mellitus; Electromagnetic Fields; Glucose; Glycated Hemoglobin; Lipids; Magnetic Fields; Rats; Transaminases; Urea; Uric Acid

To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes.. 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing.. 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome.. Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management.. NCT04427189.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Mass Screening; Registries

Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes mellitus occurring primarily in tropical countries like Bangladesh and has distinct characteristics. The present study aimed to describe the demographic, clinical and biochemical characteristics of patients with FCPD. This cross-sectional study was conducted at Mymensingh Medical College Hospital, Bangladesh, from January 2019 to December 2021. All patients with FCPD (previously or newly diagnosed) admitted to the inpatient Endocrinology department of the hospital were evaluated. Out of the 15 patients, 73.3% were aged 10-29 years at diagnosis, the male: female ratio was 11:4, rural: urban ratio was 9:6, 20.0% had FCPD in the first-degree family members, 73.3% were underweight, none were overweight/obese or central obese and one of them was hypertensive. Diabetes was uncontrolled in all, with a mean HbA1c of 10.5±1.9%. All but one had low C-peptide and all required insulin to manage diabetes. Although their average (mean or median) lipid parameters were normal, 73.3% of them had dyslipidemia. Among diabetic complications, diabetic nephropathy (66.7%) and neuropathy (66.7%) were more frequent, whereas diabetic retinopathy (6.7%), ischemic heart disease (6.7%) and peripheral vascular disease (6.7%) were less frequently observed; 13.3% had a history of diabetic ketoacidosis. Malnutrition manifested as abnormal skin and hair conditions and anemia was also common in the study subjects. Patients with FCPD are usually young males from rural residences. Microvascular diabetic complications are common, but macrovascular complications and DKA can occur in FCPD.

Topics: Bangladesh; C-Peptide; Cross-Sectional Studies; Demography; Diabetes Complications; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Lipids; Male; Obesity

Immune checkpoint inhibitor (ICI) associated diabetes is a harmful adverse event (AE) in patients with cancer following anti-programmed (cell) death protein-1 (PD-1) treatment. There are no available biomarkers able to predict this AE. The primary aim of this study was to investigate C-peptide levels as potential predictor for the occurrence of ICI-related diabetes. The secondary aim was to describe the presence of islet autoantibodies and course of pancreatic enzymes in patients with and without ICI-related diabetes.. From a total of 1318 patients with cancer who started anti-PD-1 treatment 8 cases and 16 controls were studied in this nested case-control study. C-peptide levels, islet autoantibodies, and pancreatic enzymes were measured in prospectively collected blood serum.. In cases versus controls, median C-peptide levels were comparable at baseline and before toxicity or at the corresponding time point in controls. No patient had C-peptide levels below reference range before toxicity onset. Two out of eight patients in the ICI-related diabetes group had positive islet autoantibodies, whereas one out of 16 patients in the control group had positive islet autoantibodies. Pancreatic enzymes were elevated before diabetes onset in one patient (13%) and in one control (6%) at the corresponding time point.. In patients developing ICI-related diabetes, changes in C-peptide levels, islet autoantibody positivity, and pancreatic enzymes before ICI-related diabetes onset seem comparable to patients without ICI-related diabetes. (NTR: NL6828).

Topics: Autoantibodies; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Neoplasms

Coronary artery ectasia (CAE) is an entity frequently associated with atherosclerotic coronary artery disease (CAD) in clinical practice. Although it has common risk factors with atherosclerotic CAD in its development, the pathophysiology of CAE is not fully known and it is not seen in every CAD suggesting that different determinants may play a pivotal role in the development of CAD. This study aimed to reveal the impact of C-peptide and diabetes mellitus (DM) on CAE and the effect of C-peptide and coronary ectasia on long-term outcomes in patients who underwent coronary angiography.. A total of 6611 patients who underwent coronary angiography were followed up retrospectively, and their major adverse cardiovascular event (MACE) status of an average of sixty months was recorded. According to their angiographic features, the patients were divided into two groups those with and without CAE. MACE development was accepted as the primary endpoint.. A total of 552 patients had CAE and MACE developed in 573 patients. Patients with CAE and higher C-peptide levels (Q4 + Q3) showed higher rates of MACE as compared to those without CAE and lower C-peptide levels (Q1 + Q2) (20.8% vs 7.6%; 70.1% vs 29.1%;. Our study revealed that a high C-peptide level is an independent risk factor for CAE and that CAE and C-peptide are independent predictors for the development of MACE.

Topics: Atherosclerosis; C-Peptide; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Diabetes Mellitus; Dilatation, Pathologic; Humans; Retrospective Studies

A structured approach in the diagnostic process of hypoglycemia is important to find the right diagnosis. The first step is to recognize the symptoms of hypoglycemia, confirming the hypoglycemia during symptoms and dissolvement of complaints once the glucose level is restored to normal. This confirms the Whipple triad. The second step is to exclude common causes. The third, and most important, step is a diagnostic fasting test. Measurement of insulin and C-peptide during hypoglycemia will guide to exogenic or endogenic causes of hyperinsulinism. Targeted additional investigation is then required. Often the underlying cause is treatable. This justifies the need to measure a well-timed serum glucose when hypoglycemia is suspected to make a quick diagnosis.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Glucose; Humans; Hyperinsulinism; Hypoglycemia; Insulin

Topics: C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; Graft Survival; Humans

Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes.. Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n = 16] and CFRD [n = 18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers.. The median (interquartile range) IAPP:C-peptide ratio was significantly (P = 0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2 = 0.399, P < 0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r = 0.683, P = 0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF.. Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

Topics: Adult; C-Peptide; Cross-Sectional Studies; Cystic Fibrosis; Diabetes Mellitus; Humans; Islet Amyloid Polypeptide; Longitudinal Studies; Prospective Studies

Decreased pancreatic volume (PV) is a predictive factor for diabetes mellitus (DM) after surgery. There are few reports on PV and endocrine function pre- and post-surgery. We investigated the correlation between PV and insulin secretion.. Seventeen patients underwent pancreaticoduodenectomy (PD) Pre- and post-surgery PV and C-peptide index (CPI) measurements were performed. Additionally, the correlation between PV and CPI was analyzed.. The mean preoperative PV (PPV) was 55.1 ± 31.6 mL, postoperative remnant PV (RPV) was 25.3±17.3 mL, and PV reduction was 53%. The mean preoperative C-peptide immunoreactivity (CPR) was 1.39 ± .51 and postoperative CPR was .85±.51. The mean preoperative CPI was 1.29±.72 and postoperative CPI was .73 ± .48. Significant correlations were observed between RPV and post CPR (ρ = .507, P = .03) and post CPI (ρ = .619, P = .008).. There was a significant correlation between RPV and CPI after PD. A smaller RPV resulted in lower insulin secretion ability, increasing the potential risk of new-onset DM after PD.

Topics: Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Male; Multidetector Computed Tomography; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Retrospective Studies

Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion.. Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function.. Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value <0.001). The hemoglobin A1c was not different between TS and HC (median 5%, p = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, <0.0001 for SI, Φ total, DI, respectively).. β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Phenotype; Prediabetic State; Prevalence; Turner Syndrome

Preproinsulin (PPI) translocation across the membrane of the endoplasmic reticulum (ER) is the first and critical step of insulin biosynthesis. Inefficient PPI translocation caused by signal peptide (SP) mutations can lead to β-cell failure and diabetes. However, the effect of proinsulin domain on the efficiency of PPI translocation remains unknown. With whole exome sequencing, we identified a novel

Topics: Adolescent; Adult; C-Peptide; Child; Codon, Nonsense; Diabetes Mellitus; Endoplasmic Reticulum; Family; Female; Humans; Insulin; Male; Middle Aged; Pedigree; Protein Precursors; Protein Transport; Young Adult

PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA.. In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated.. Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032).. PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

Topics: Adult; Aniridia; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Heterozygote; Humans; Insulin; Male; Middle Aged; Mutation; PAX6 Transcription Factor; Proinsulin

To investigate how markers of beta-cell secretion (proinsulin-processing metabolites) are expressed in SLE patients and their potential relation to features associated with the disease such as activity or damage.. One hundred and forty-four SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analysed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors.. Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy [beta coeficient 0.19 (95% Confidence Interval 0.07, 0.30), P = 0.002] or not [beta coef. 0.09 (95% CI: 0.01, 0.17), P = 0.025]. Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids [beta coef. 0.08 (95% CI: 0.03, 0.12), P = 0.001]. SLE damage score was associated with higher serum levels of intact [beta coef. 0.51 (95% CI 0.17, 0.86) pmol/l, P = 0.004] and split proinsulins [beta coef. 1.65 (95% CI 0.24, 3.06) pmol/l, P = 0.022] after multivariable analysis, including disease duration and prednisone use.. Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucocorticoids; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Lupus Erythematosus, Systemic; Male; Middle Aged; Proinsulin

Until now, diabetes during pregnancy has been associated with a high risk of maternal, fetal, and neonatal morbidities and mortalities. The main aim of this study was to evaluate the risk factors of hypoglycemia in infants of diabetic mothers (IDMs) and to study the relationship between umbilical cord (UC) C peptide levels and the risk of developing hypoglycemia.. UC blood C-peptide and serial serum blood glucose measurements were done for all included singleton newborns born to diabetic mothers during the study period. Maternal and neonatal data such as gestational age, maternal age, maternal weight, types of diabetics and its control, maternal glycated hemoglobin (HbA1C), birth weight, Apgar score, and neonatal complete blood picture were collected.. In total, 83 IDMs met the inclusion criteria. Fifty-four (65.06%) developed hypoglycemia and 29 (34.94%) remained normoglycemic. However, there were no significant differences between hypoglycemic and normoglycemic IDMs in terms of types of maternal diabetics (P value = 0.41), its duration (P value = 0.43). The hypoglycemia peak occurred within the first 3 h of life, with 33.11 ± 8.84 mg/dl for the hypoglycemia group and 54.10 ± 6.66 mg/dl for the normoglycemic group (P value < 0.0001). Most of the babies had no hypoglycemic manifestation (96.30%). Neonates with hypoglycemia their mothers had poor diabetes control in the last trimester (HbA1C 7.09 ± 0.96%) compared to normoglycemic babies (HbA1C 6.11 ± 0.38%), (P-value < 0.0001). The mean (SD) of UC C-peptide level in hypoglycemic neonates increased to 1.73 ± 1.07 ng/ml compared to normoglycemic ones with 1.08 ± 0.81 ng/ml (P value = 0.005).. Poor diabetes control, especially in the last trimester, is associated with neonatal hypoglycemia. Increased UC C-peptide levels could be used as an early indicator for the risk of developing neonatal hypoglycemia and a predictor for babies need neonatal admission.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes, Gestational; Female; Humans; Hypoglycemia; Infant; Infant, Newborn; Mothers; Pregnancy; Pregnancy in Diabetics; Umbilical Cord

In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels-occurring as the result of glucose infusion or food intake-could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c-peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Eating; Glucagon; Glucose Clamp Technique; Hypoglycemic Agents; Insulin; Insulin Aspart; Male; Swine

Autoimmune pancreatitis (AIP) is frequently complicated by diabetes mellitus (DM), but DM associated with AIP is reported to improve after steroid therapy. The aim of this study is to investigate glucose intolerance during steroid therapy according to the onset of DM.. Sixty-one patients who underwent steroid therapy for AIP were included into this study. We evaluated C peptide index (CPI), homeostasis model assessment for insulin resistance (HOMA-R), and the pancreatic diameter at AIP diagnosis and after 4 weeks, 1 year, and 2 years of steroid therapy. Patients were categorized into three groups according to DM onset: Pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM).. Forty-three patients (71%) had DM: 15 pDM and 28 cDM. At AIP diagnosis, CPI was lower in patients with pDM (0.7, P = 0.007) and cDM (0.9, P = 0.018) than nDM (1.3). After 4 weeks of steroid therapy, CPI improved in cDM (P < 0.001) and in nDM (P = 0.021). After 2 years of steroid therapy, HOMA-R increased (2.1-3.0, P = 0.007) but CPI gradually improved (1.0-2.1, P = 0.004). DM improved in 23% of cDM, and 55% of insulin users in cDM discontinued using insulin. Pancreatic atrophy was seen in 30%, and was associated with DM.. DM in patients with AIP was associated with impaired insulin secretion rather than insulin resistance. Insulin secretion improved during steroid therapy for AIP in patients with concurrent DM. Thus, glucose intolerance can be an indication for AIP treatment.

Topics: Aged; Anti-Inflammatory Agents; Atrophy; Autoimmune Pancreatitis; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Intolerance; Homeostasis; Humans; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Pancreas; Prednisolone

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; C-Peptide; Child; Diabetes Complications; Diabetes Mellitus; Dietary Supplements; Female; Glucose Tolerance Test; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Iron Chelating Agents; Male; Metformin; Middle Aged; Pilot Projects; Thalassemia; Young Adult; Zinc; Zinc Sulfate

Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT).. Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models.. The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint.. Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Topics: Acute Disease; Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Diseases; Middle Aged; Pancreatic Hormones; Pancreatitis; Prediabetic State; Prevalence

Topics: Aged; Atrophy; Autoantibodies; C-Peptide; Diabetes Mellitus; Humans; Immunologic Factors; Insulin; Interferon-alpha; Male; Polycythemia Vera; Subcutaneous Fat

Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes.. We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC).. Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001].. Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.

Topics: Adult; Age of Onset; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Genetic Predisposition to Disease; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Reproducibility of Results; Young Adult; Zinc Transporter 8

Islet transplantation has been proved to be effective in delaying early stage of DN. This study was established to observe the mechanism of islet transplantation on early diabetic nephropathy (DN).. The diabetes mellitus (DM) rat model was established by an injection of a single-dose streptozotocin. According to the treatment, the rats were randomly divided into 4 groups: the untreated DN rats (DN group); the C-peptide treated rats (CP group); the islet transplanted rats (IT group); the normal control rats (NC group). Renal function and structure of glomerular filtration barrier (GFB) were evaluated by urinalysis and histopathological examination, respectively. The renal fibrotic factors, TGF- β1 and CTGF, as well as the anti-renal fibrosis factor HGF were assessed by immunohistochemical staining and western blotting methods.. After C-peptide treatment and islet transplantation, the GFB structure was obviously improved. The blood glucose significantly decreased in the IT group. The 24h urine protein and glomerular basement membrane thickness decreased, the pathological changes of podocytes improved, TGF- β1 and CTGF decreased and HGF increased in the CP group and the IT group compared with that in the DN group (P < 0.05), especially in the IT group.. Islet transplantation could ameliorate the structure of GFB of early DN in a rat model, and the treatment effect was partly attributed to the restoration of C-peptide concentration. Suppressing the fibrosis system can be the potential mechanism of islet transplantation, which is independent of blood glucose control.

Topics: Animals; C-Peptide; Diabetes Mellitus; Diabetic Nephropathies; Disease Models, Animal; Fibrosis; Glomerular Filtration Barrier; Humans; Islets of Langerhans Transplantation; Male; Rats; Rats, Sprague-Dawley; Streptozocin; Transforming Growth Factor beta1; Urinalysis

Serum C-peptide concentrations reflect insulin secretion and beta cell function and can be used to diagnose and distinguish type-1 and type-2 diabetes. C-peptide is a more accurate indicator of insulin status than direct insulin measurement for monitoring patients with diabetes. However, the current methods available for C-peptide quantification exhibit poor reproducibility, are costly, and require highly trained laboratory personnel. Here, we have developed and evaluated a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based assay to standardize C-peptide measurements, providing highly accurate and comparable results across testing systems and laboratories.. C-peptide from human serum was enriched using antibody-conjugated magnetic beads. The eluted isolates were further modified with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) to enhance the ionization of naturally acidic C-peptide. After desalting with ZipTips, the samples were subjected to MALDI-TOF MS analysis. Recombinant human C-peptide was used to develop the assay, and a heavy isotope labeled human C-peptide was used as an internal standard for quantification.. The MALDI-TOF MS method was validated in accordance with the restrictions of the device, with a limit of quantitation of 25 pmol/L. A correlation between the MAL-DI-TOF MS assay and a reference method was conducted using patient samples. The resulting regression revealed good agreement.. A simple, high-throughput, cost effective and quantitative MALDI-TOF MS C-peptide assay has been successfully developed and validated in clinical serum samples.

Topics: Aminoquinolines; Antibodies, Immobilized; C-Peptide; Carbamates; Diabetes Mellitus; Humans; Limit of Detection; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To investigate the incretin axis in people with cystic fibrosis.. Adults with cystic fibrosis-related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C-peptide, total and active glucagon-like peptide-1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min.. Five adults with cystic fibrosis-related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis-related diabetes group (cystic fibrosis-related diabetes vs control group: -6% vs 28%; p=0.03). No hyposecretion of glucagon-like peptide-1 or gastric inhibitory polypeptide was observed; conversely, 60-min incremental area under the curve for total glucagon-like peptide-1 was significantly higher in the cystic fibrosis-related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] CONCLUSIONS: The incretin effect was lost in cystic fibrosis-related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis-related diabetes.

Topics: Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Hyperglycemia; Incretins; Infusions, Intravenous; Insulin; Male

Islet xenotransplantation is a promising treatment for type I diabetes. Numerous studies of islet xenotransplantation have used pig-to-nonhuman primate transplantation models. Some studies reported long-term survival and successful function of porcine islets in diabetic monkeys. Genetic engineering techniques may improve the survival and function of porcine islets. A recent study reported the generation of transgenic pigs expressing human insulin rather than porcine insulin by changing one amino acid at the end of the β-chain in insulin. However, C-peptide from pigs still existed. In this study, we generated transgenic pigs expressing human proinsulin to express human insulin and C-peptide using fibroblasts from proinsulin knockout pigs as donor cells for somatic cell nuclear transfer. Eleven live piglets were delivered from three surrogates and characterized to confirm the genotype and phenotype of the generated piglets. Genotype analysis of the generated piglets showed that five of the eleven piglets contained the human proinsulin gene. Insulin expression was confirmed in the serum and pancreas in two of the five piglets. C-peptide derived from human proinsulin was also confirmed by liquid chromatography tandem mass spectrometry. Non-fasting blood glucose level was measured to verify the function of the insulin derived from the human proinsulin. Two piglets expressing insulin showed normal glucose levels similar to that in the wild-type control. In conclusion, human insulin- and C-peptide-expressing pigs without porcine insulin and C-peptide were successfully established. These pigs can be used as a source of islets for islet xenotransplantation.

Topics: Animals; Animals, Genetically Modified; Blood Glucose; C-Peptide; Diabetes Mellitus; Fibroblasts; Gene Knockout Techniques; Genetic Engineering; Humans; Insulin; Islets of Langerhans Transplantation; Swine; Transplantation, Heterologous

Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP).. In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models.. Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05).. We observed a measurable decline in β-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Progression; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatic Diseases; Pancreatitis, Chronic; Risk Factors; Young Adult

The loss of pancreatic β-cells is a cause of diabetes. Therefore, replacement of pancreatic β-cells is a logical strategy for the treatment of diabetes, and the generation of insulin-producing cells (IPCs) from stem cells has been widely investigated as an alternative source for pancreatic β-cells. Here, we isolated stem cells from human urine and investigated their differentiation potential into IPCs. We checked the expression of surface stem cell markers and stem cell transcription factors, and found that the isolated human urine-derived stem cells (hUDSCs) expressed the stem cell markers CD44, CD90, CD105 and stage-specific embryonic antigen (SSEA)-4. In addition, these cells expressed octamer binding transcription factor (Oct)4 and vimentin. hUDSCs could differentiate into adipocytes and osteocytes, as evidenced by Oil-red O staining and Alizarin Red S-staining of differentiated cells, respectively. When we directly differentiated hUDSCs into IPCs, the differentiated cells expressed mRNA for pancreatic transcription factors such as neurogenin (Ngn)3 and pancreatic and duodenal homeobox (Pdx)1. Differentiated IPCs expressed insulin and glucagon mRNA and protein, and these IPCs also secreted insulin in response to glucose stimulation. In conclusion, we found that hUDSCs can be directly differentiated into IPCs, which secrete insulin in response to glucose.

Topics: Adipocytes; C-Peptide; Cell Differentiation; Diabetes Mellitus; Glucose; Humans; Insulin; Insulin-Secreting Cells; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pancreas; Urine

Background Too much consumption of carbonated beverages increases the risk of diabetes. Insulin deficiency and the body's decreased sensitivity to insulin cause diabetes. C-peptide can assess a person's own insulin secretion. The decrease of C-peptide is closely related to the occurrence of diabetes and its chronic complications. The present study assessed the effect of carbonated beverages on C-peptide in adolescents and analyzed the correlation between C-peptide and the drinking index (DI). Methods The subjects investigated including 463 adolescents were divided into a carbonated beverages group, a non-carbonated beverages group and a control group. The general demographic characteristics, beverage consumption status, physical activity and family history of hypertension and diabetes were interviewed with a questionnaire designed by us. All the subjects maintained their original lifestyle and received the oral glucose tolerance test. Various biochemical indicators and C-peptides were detected in these three groups. The data were analyzed by statistical analysis, and multivariate logistic regression analysis was used to examine the risk factors related to C-peptide. Results Blood glucose, blood lipid, liver function and renal function had no statistically significant difference among the three groups. C-peptide levels were lower in the carbonated beverages group and the non-carbonated beverages group than in the control group. Compared to the non-carbonated beverages group, there was a significant decrease in C-peptide levels in the carbonated beverages group. Logistic analysis demonstrated that DI was negatively correlated with C-peptide levels when the physical activity was adjusted. The odds ratio (OR) (OR = 2.540, 95% confidence interval [CI] 1.121-5.752) value difference was statistically significant at a stratification level of DI ≥ 6. Conclusions The C-peptide of adolescents was affected by the long-term consumption of beverages, and the effect of carbonated beverages was even more obvious. DI ≥ 6 bottle-years was a risk factor for diabetes, and we can constitute prevention and control measures accordingly so as to reduce the incidence of diabetes.

Topics: Adolescent; Adult; C-Peptide; Carbonated Beverages; Case-Control Studies; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Prognosis; Risk Factors; Young Adult

Microsampling techniques are alternative methods to venous sampling for obtaining blood for measurement of circulating biomarkers, offering the convenience of reduced sample volume and elimination of the need for phlebotomists. Dried blood spot (DBS) microsampling methods have been used for many years while more recently a volumetric absorptive microsampling device (VAMS™) has been introduced. In diabetes mellitus, circulating C-peptide is commonly used as an indicator of endogenous insulin secretion and clinical measurement can aid in diagnosis as well as informing on therapy. This pilot study investigated the effectiveness of microsampling collection of capillary blood for measurement of C-peptide.. Capillary blood was collected into capillary tubes and centrifuged for plasma samples. Simultaneous samples were also collected using both microsampling methods (DBS and VAMS). Blood from both microsamplers was extracted prior to assaying for C-peptide alongside the corresponding plasma samples, using specific immunoassays and results obtained from microsampling compared to the reference plasma concentrations. Stability was determined by collecting duplicate DBS and VAMS and assaying both in a single assay after storing one at -20°C immediately and one at room temperature for 48 hours post-collection.. C-peptide collected using DBS and VAMS showed good agreement with reference plasma concentrations, suggesting both would be an effective microsampling method for collection and measurement of C-peptide.

Topics: Blood Specimen Collection; C-Peptide; Diabetes Mellitus; Dried Blood Spot Testing; Healthy Volunteers; Humans; Pilot Projects

Cystic fibrosis-related diabetes (CFRD) is the most frequent extrapulmonary complication of cystic fibrosis (CF).. We report the first combined pancreatic islet-lung-liver transplantation in a 14-year-old adolescent. CFTR was analyzed by Sanger sequencing. Further genes were analyzed by high-throughput sequencing.. The patient was diagnosed with CF at the age of 14 months. Nine years later, after diagnosis of CFRD, the patient's BMI and lung function began to decline. Bilateral lung transplantation with simultaneous liver transplantation was performed at the age of 14.5 years. The first islet transplantation (IT) was carried out 10 days later. Six months later, C-peptide secretion after arginine stimulation showed peak values of 371 pmol/L (vs. 569 pmol/L before IT) and insulin doses had slightly increased (1.40 vs. 1.11 units/kg/day before IT). A second IT was performed at the age of 15 years, a third at 16 years. Two years after the first IT, arginine-stimulated C-peptide secretion increased to 2,956 pmol/L and insulin doses could be reduced to 0.82 units/kg/day. HbA1c decreased from 7.3% (57.4 mmol/mol) to 5.9% (41.0 mmol/mol).. IT following lung and liver transplantation, with injection of islets into a transplanted organ, is feasible. It improves C-peptide secretion, decreases insulin needs, and lowers HbA1c.

Topics: Adolescent; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans Transplantation; Liver Transplantation; Lung Transplantation; Male

Diabetes mellitus (DM) is prevalent in patients with pancreatic cancer and tends to improve after tumor resection. However, the glycemic response of non-pancreatic cancer patients after surgery has not been examined in detail. We aimed to investigate the changes in glucose metabolism in patients with pancreatic cancer or non-pancreatic cancer after pancreatoduodenectomy (PD).We prospectively enrolled 48 patients with pancreatic cancer and 56 patients with non-pancreatic cancer, who underwent PD. Glucose metabolism was assessed with fasting glucose, glycated hemoglobin (HbA1c), plasma C-peptide and insulin, quantitative insulin check index (QUICKI), and a homeostatic model assessment of insulin resistance (HOMA-IR) and β cell (HOMA-β) before surgery and 6 months after surgery. Patients were divided into 2 groups: "improved" and "worsened" postoperative glycemic response, according to the changes in HbA1c and anti-diabetic medication. New-onset DM was defined as diagnosis of DM ≤ 2 years before PD, and cases with DM diagnosis >2 years preceding PD were described as long-standing DM.After PD, insulin resistance (IR), as measured by insulin, HOMA-IR and QUICKI, improved significantly, although C-peptide and HOMA-β decreased. At 6 months after PD, new-onset DM patients showed improved glycemic control in both pancreatic cancer patients (75%) and non-pancreatic cancer patients (63%). Multivariate analysis showed that long-standing DM was a significant predictor for worsening glucose control (odds ratio = 4.01, P = .017).Favorable glycemic control was frequently observed in both pancreatic cancer and non-pancreatic cancer after PD. PD seems to contribute improved glucose control through the decreased IR. New-onset DM showed better glycemic control than long-standing DM.

Topics: Aged; Ampulla of Vater; Blood Glucose; C-Peptide; Common Bile Duct Neoplasms; Diabetes Mellitus; Duodenal Neoplasms; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy

C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women.. A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement.. Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively).. This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Topics: Aged; Biomarkers; Bone Density; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Italy; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Prevalence; Prognosis; Risk Factors

As both of peripheral arterial disease (PAD) and depression carried a poor prognosis in patients on maintenance hemodialysis (MHD), we investigated the correlation between the ankle-brachial index (ABI), an indicator of subclinical PAD, and symptoms of depression in patients on MHD.. One hundred and twenty-nine patients on MHD (75 males and 54 females, mean age 64.8 ± 12 years) were enrolled in this cross-sectional study, which aimed at evaluating the relationship between symptoms of depression and ABI. Demographic as well as clinical and laboratory variables including status of diabetes, chronic hepatitis C infection, dialysis duration, Charlson comorbidity index (CCI), plasma levels of albumin, C-peptide, insulin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin, and lipid profile were obtained. The self-administered beck depression inventory (BDI) was used to determine the presence or absence of symptoms of depression, and depression was defined as a BDI score ≧14. Multivariable-adjusted linear regression models were constructed to confirm the independent association of biologic parameters of symptoms of depression. Significance was defined as P < 0.05. Statistical analyses were performed using SPSS/Windows software (SPSS Science, v. 15.0, Chicago, IL).. The mode of multivariate analysis showed that diabetes (β = 3.594; P = 0.040), hepatitis C infection (β = 4.057; P = 0.008), levels of serum albumin (β = -5.656; P = 0.024), C-peptide (β = -0.292; P = 0.002), ABI (β = -9.041; P = 0.031), and Ln-transformed hsCRP were significantly associated with BDI.. Hepatitis C infection, serum levels of albumin, C-peptide, and ABI levels were found to be correlated with BDI (P < 0.05).

Topics: Aged; Ankle Brachial Index; C-Peptide; C-Reactive Protein; Cross-Sectional Studies; Depression; Diabetes Mellitus; Female; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peripheral Arterial Disease; Psychiatric Status Rating Scales; Renal Dialysis; Serum Albumin; Symptom Assessment

Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY. In vivo studies of these mutations may lead to a better understanding of insulin mutation-associated diabetes and point to the best treatment strategy. We studied an 18-year-old woman with MODY heterozygous for the insulin mutation p.R46Q (GlnB22-insulin), measuring the secretion of mutant and wild-type insulin by LC-MS. The clinical study was combined with in vitro studies of the synthesis and secretion of p.R46Q-insulin in rat INS-1 insulinoma cells.. We performed a standard 75 g OGTT in the 18-year-old woman and measured plasma glucose and serum insulin (wild-type insulin and GlnB22-insulin), C-peptide, proinsulin, glucagon and amylin. The affinity of GlnB22-insulin was tested on human insulin receptors expressed in baby hamster kidney (BHK) cells. We also examined the subcellular localisation, secretion and impact on cellular stress markers of p.R46Q-insulin in INS-1 cells.. Plasma GlnB22-insulin concentrations were 1.5 times higher than wild-type insulin at all time points during the OGTT. The insulin-receptor affinity of GlnB22-insulin was 57% of that of wild-type insulin. Expression of p.R46Q-insulin in INS-1 cells was associated with decreased insulin secretion, but not induction of endoplasmic reticulum stress.. The results show that beta cells can process and secrete GlnB22-insulin both in vivo and in vitro. Our combined approach of immunoprecipitation and LC-MS to measure mutant and wild-type insulin may be useful for the study of other mutant insulin proteins. The ability to process and secrete a mutant protein may predict a more benign course of insulin mutation-related diabetes. Diabetes develops when the beta cell is stressed because of increased demand for insulin, as observed in individuals with other insulin mutations that affect the processing of proinsulin to insulin or mutations that reduce the affinity for the insulin receptor.

Topics: Adolescent; Animals; Blotting, Western; C-Peptide; Cell Line; Cricetinae; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Islet Amyloid Polypeptide; Proinsulin; Rats; Receptor, Insulin

Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease.. We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events.. We performed a mean follow-up of 56 months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p < 0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors.. C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker.

Topics: Aged; Atherosclerosis; Biomarkers; C-Peptide; Cause of Death; Chronic Disease; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Linear Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Proportional Hazards Models; Registries; Risk Factors; Time Factors

Serum CA19-9 level is a sensitive marker for pancreatic tissue damage; however, its correlation factors are still unclear in diabetic patients. This study was aimed to investigate the correlation factors of serum CA 19-9 levels in these patients.. Based on their serum CA19-9 levels, 412 diabetic patients (57 type 1 and 355 type 2) were divided into the negative group (432 cases, CA19-9 37 U /ml) and the positive group (31 cases, CA19-9 ≥ 37 U /ml). The two groups were compared with age, sex, duration of diabetic history, hemoglobin A1c, blood lipid, fasting C-peptide level, and area under the curve C-peptide. The difference was significant between 2 groups in age, hemoglobin A1c, total cholesterol, highdensity lipoprotein cholesterol, fasting C-peptide level, and area under the curve C-peptide (P < 0.05). A multivariate linear regression model found that the type of diabetes, hemoglobin A1c, area under the curve C-peptide, and high-density lipoprotein cholesterol are the independent contributors to CA19-9 levels.. The results indicated that CA19-9 levels in patients with diabetes mellitus were related to not only age and sex but also diabetic type, hemoglobin A1c, lipid metabolism, and pancreatic beta cell function.

Topics: Adolescent; Adult; Antigens, Tumor-Associated, Carbohydrate; C-Peptide; China; Cholesterol; Cholesterol, HDL; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Insulin-Secreting Cells; Linear Models; Lipid Metabolism; Male; Middle Aged; Multivariate Analysis; Young Adult

Over the last 20 years, proinsulin C-peptide emerged as an important player in various biological events. Much time and effort has been spent in exploring all functional features of C-peptide and recording its implications in Diabetes mellitus. Only a few studies, though, have addressed C-peptide oligomerization and link this procedure with Diabetes. The aim of our work was to examine the aggregation propensity of C-peptide, utilizing Transmission Electron Microscopy, Congo Red staining, ATR-FTIR, and X-ray fiber diffraction at a 10 mg ml

Topics: Amino Acid Sequence; Amyloid; C-Peptide; Congo Red; Diabetes Mellitus; Humans; Insulin; Microscopy, Electron, Transmission; Microscopy, Polarization; Microscopy, Video; Protein Aggregation, Pathological; Protein Conformation; Protein Multimerization; Spectroscopy, Fourier Transform Infrared; Staining and Labeling; X-Ray Diffraction

Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation.. We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant.. Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.. At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Topics: Acute Disease; Adult; C-Peptide; Cohort Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Health Facilities; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Postoperative Complications; Recurrence; Retrospective Studies; Transplantation, Autologous; Treatment Outcome

Human proinsulin with C-peptide-bearing Superfolder Green Fluorescent Protein (CpepSfGFP) has been expressed in transgenic mice, driven by the Ins1 promoter. The protein, expressed exclusively in β-cells, is processed and stored as CpepSfGFP and human insulin comprising only ∼0.04% of total islet proinsulin plus insulin, exerting no metabolic impact. The kinetics of the release of insulin and CpepSfGFP from isolated islets appear identical. Upon a single acute stimulatory challenge in vitro, fractional release of insulin does not detectably deplete islet fluorescence. In vivo, fluorescence imaging of the pancreatic surface allows, for the first time, visual assessment of pancreatic islet insulin content, and we demonstrate that CpepSfGFP visibly declines upon diabetes progression in live lepR(db/db) mice. In anesthetized mice, after intragastric or intravenous saline delivery, pancreatic CpepSfGFP (insulin) content remains undiminished. Remarkably, however, within 20 min after acute intragastric or intravenous glucose delivery (with blood glucose concentrations reaching >15 mmol/L), a small subset of islets shows rapid dispossession of a major fraction of their stored CpepSfGFP (insulin) content, whereas most islets exhibit no demonstrable loss of CpepSfGFP (insulin). These studies strongly suggest that there are "first responder" islets to an in vivo glycemic challenge, which cannot be replicated by islets in vitro.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Progression; Glucose; Green Fluorescent Proteins; Humans; In Vitro Techniques; Insulin-Secreting Cells; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Proinsulin

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely.. We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment.. Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea.. During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glyburide; Humans; Hyperglycemia; Infant; Infant, Newborn; Insulin; Insulin Infusion Systems; Male; Monitoring, Physiologic; Sulfonylurea Compounds

Mitochondrial diabetes is a rare form of diabetes mellitus accounting for up to 1% of all diabetes. Pyruvate therapy has been reported to be a potential therapeutic choice for patients with mitochondrial diseases.. Water-based sodium pyruvate solutions (0.5 g/kg, thrice daily) were administrated orally to a 32-year-old Japanese male with mitochondrial diabetes and myopathy caused by m.14709T>C mutation. At the age of 20 years, he was diagnosed with diabetes mellitus and started insulin therapy. He tested negative for islet cell and glutamic decarboxylase antibodies. To evaluate favorable therapeutic improvements, we measured the lactate and pyruvate levels in plasma and cerebrospinal fluid; urinary C-peptide, glycated hemoglobin, and glycoalbumin levels; and total daily insulin dose (TDD). The patient experienced no side effects such as diarrhea because of pyruvate therapy. His urinary C-peptide level improved from 4.3 to 17.2 μg/d after 1 day and to 30.2 μg/d after 6 months of pyruvate therapy. TDD decreased from 33 to 20 U/d after 6 months of pyruvate therapy, but the lactate levels of plasma and cerebrospinal fluid and the lactate/pyruvate ratio did not change.. Sodium pyruvate improved insulin secretion and resulted in decreased TDD in a patient with mitochondrial diabetes. Pyruvate therapy may be a potential therapeutic choice for patients with mitochondrial diabetes. Clinical trials involving a larger number of patients and long-term evaluation of the therapy are necessary to clarify the efficacy of pyruvate therapy.

Topics: Adult; C-Peptide; Diabetes Mellitus; Humans; Insulin; Male; Mitochondrial Diseases; Mutation; Pyruvic Acid; Treatment Outcome

Topics: Animals; C-Peptide; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Proinsulin

Diabetes mellitus is a frequent consequence of chronic pancreatitis (CP). Little is known about pancreatic endocrine function before the development of diabetes mellitus in CP, particularly in females, or those without calcific and/or alcoholic pancreatitis.. Twenty-five nondiabetic adult patients with CP (19 female; mean [SE] age, 34.2 [2.4] years) were compared with 25 healthy controls matched for age, sex, and body mass index. Subjects underwent frequent sample intravenous glucose tolerance testing (FSIVGTT) and mixed meal tolerance testing (MMTT).. Mean (SE) fasting glucose was higher in patients with CP (89.5 [2.3] mg/dL) than in controls (84.4 [1.2] mg/dL, P = 0.04). On MMTT, patients with CP had a higher area under the curve (AUC) glucose and AUC glucagon compared with controls (P ≤ 0.01). The AUC C-peptide was equivalent (P = 0.6) but stimulated C-peptide at 30 minutes was lower in patients with CP (P = 0.04). Mean insulin sensitivity index calculated from the FSIVGTT was lower in CP group, indicating reduced insulin sensitivity (P ≤ 0.01). Disposition index (insulin secretion adjusted for insulin sensitivity on FSIVGTT) was lower in patients with CP (P = 0.01).. Patients with CP had higher fasting and MMTT glucose levels, without a compensatory increase in insulin secretion suggesting subtle early islet dysfunction. Our cohort had relative hyperglucagonemia and was less insulin sensitive than controls.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Progression; Fasting; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis, Chronic

Islet transplantation has been hampered by the shortage of islet donors available for diabetes therapy. However, pluripotent stem cells (PSCs) can be an alternative source of insulin-producing cells (IPCs) because of their capacity for self-renewal and differentiation. We described a method to efficiently differentiate PSCs into IPCs by co-culturing mature islets with directed-differentiated pancreatic endoderm (PE) cells from mouse and human PSCs. PE cells co-cultured with islet cells or islet cell-derived conditioned medium (CM) showed increased expression levels of β-cell markers; significantly higher levels of proinsulin- and Newport Green (NG)-positive cells, which revealed the characteristics of insulin producing cells; and increased insulin secretion upon glucose stimulation. Co-culturing human PE cells with islet cells was also effective to differentiate PE cells into IPCs. Diabetic nude mice transplanted with co-cultured cells exhibited restored euglycemia, human C-peptide release, and improved glucose tolerance. Immunohistochemistry revealed that insulin+/C-peptide + cells existed in the grafted tissues. These results suggest that mature islet cells can increase the differentiation efficiency of PE cells into mature IPCs via paracrine effects.

Topics: Animals; Biomarkers; Blood Glucose; C-Peptide; Cell Differentiation; Cells, Cultured; Coculture Techniques; Diabetes Mellitus; Embryonic Stem Cells; Endoderm; Gene Expression; Humans; Insulin; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Islets of Langerhans; Mice, Nude; Microscopy, Electron; Microscopy, Fluorescence; Pancreas; Pluripotent Stem Cells; Proinsulin; Reverse Transcriptase Polymerase Chain Reaction

In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass.. It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density.. Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay.. rteen percent of the population had osteoporosis and 38% had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013).. These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.

Topics: Absorptiometry, Photon; Aged; Biomarkers; Body Mass Index; Bone Density; Bone Diseases, Metabolic; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Sensitivity and Specificity

In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT).. We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥ 2.0 ng/mL or < 2.0 ng/mL.. From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥ 2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥ 5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2).. Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be used exclusively to determine candidacy for SPKT.

Topics: Adult; Biomarkers; C-Peptide; Diabetes Mellitus; Disease Progression; Female; Follow-Up Studies; Graft Survival; Humans; Male; North Carolina; Pancreas Transplantation; Preoperative Period; Prognosis; Retrospective Studies; Survival Rate

Topics: C-Peptide; Diabetes Mellitus; Female; Humans; Male; Pancreas Transplantation

To investigate the characteristics of immunological hypoglycemia associated with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients with diabetes.. The clinical data of patients with immunological hypoglycemia due to IAbs were retrospectively analyzed by screening patients with diabetes discharged from West China Hospital from 2007 to 2013.. A total of 11 patients (eight men and three women) were identified. Insulin-C-peptide separation was found in all patients via insulin and C-peptide release test. Previous insulin use was ceased after admission and was switched to oral hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days (interquartile range [IQR], 11-40), while IAbs turned negative after a median of 17 months (IQR, 4-19), and serum immunoreactive insulin (IRI) levels dropped substantially after a median of 22 months (IQR, 9-32) in these cases.. In insulin-treated patients with unexpected and refractory hypoglycemia even after insulin therapy was gradually reduced or even withdrawn, IAbs induced by exogenous insulin should be considered, and insulin withdrawal might be promptly needed. The course of immunological hypoglycemia was benign and self-limited.

Topics: Aged; Blood Glucose; C-Peptide; China; Diabetes Mellitus; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Male; Middle Aged; Retrospective Studies

Topics: Adolescent; Biomarkers; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Humans; Male

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Drug Substitution; Glyburide; Humans; Hypoglycemic Agents; Male; Mutation; Potassium Channels, Inwardly Rectifying; Sulfonylurea Compounds; Treatment Failure; Young Adult

This study investigated the differentiation of human amniotic fluid-derived stem cells (hAFSCs) into insulin-producing clusters in vitro. Adenovirally-delivered mouse Pdx1 (Ad-Pdx1) induced human Pdx1 expression in hAFSCs and enhanced the coordinated expression of downstream β-cell markers. When Ad-Pdx1-transduced hAFSCs were sequentially treated with activin A, bFGF and nicotinamide and the culture plate surface coated with poly-l-ornithine, the expression of islet-associated human mRNAs for Pdx1, Pax6, Ngn3 and insulin was increased. C-peptide ELISA confirmed that Ad-Pdx1-transduced hAFSCs processed and secreted insulin in a manner consistent with that pathway in pancreatic β-cells. To sustain the β-cell-like phenotype and investigate the effect of three-dimensional (3D) conformation on the differentiation of hAFSCs, Pdx1-transduced cells were encapsulated in alginate and cultured long-term under serum-free conditions. Over 2 weeks, partially differentiated hAFSC clusters increased in size and increased insulin secretion. Taken together, these data demonstrate that ectopic Pdx1 expression initiates pancreatic differentiation in hAFSCs and that a β-cell-like phenotype can be augmented by culture conditions that mimic the stromal components and 3D geometry associated with pancreatic islets.

Topics: Adenoviridae; Amniotic Fluid; Animals; C-Peptide; Cell Culture Techniques; Cell Differentiation; Cell- and Tissue-Based Therapy; Culture Media; Culture Media, Serum-Free; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Mice; Stem Cells; Trans-Activators

The Diabetes Control and Complications Trial established that a stimulated C-peptide concentration ≥0.2 nmol/L at study entry among subjects with up to a 5-year diabetes duration is associated with favorable metabolic and clinical outcomes over the subsequent 7 years of follow-up. Herein we further examine the association of both fasting and stimulated C-peptide numerical values with outcomes. In the intensive treatment group, for a 50% higher stimulated C-peptide on entry, such as from 0.10 to 0.15 nmol/L, HbA1c decreased by 0.07% (0.8 mmol/mol; P = 0.0003), insulin dose decreased by 0.0276 units/kg/day (P < 0.0001), hypoglycemia risk decreased by 8.2% (P < 0.0001), and the risk of sustained retinopathy was reduced by 25% (P = 0.0010), all in unadjusted analyses. Other than HbA1c, these effects remained significant after adjusting for the HbA1c on entry. While C-peptide was not significantly associated with the incidence of nephropathy, it was strongly associated with the albumin excretion rate. The fasting C-peptide had weaker associations with outcomes. As C-peptide decreased to nonmeasurable concentrations, the outcomes changed in a nearly linear manner, with no threshold or breakpoint. While preservation of stimulated C-peptide at ≥0.2 nmol/L has clinically beneficial outcomes, so also does an increase in the concentration of C-peptide across the range of values.

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Time Factors; Young Adult

Diabetes mellitus is a chronic disease affecting millions of people globally and resulting in significant death rates each year. A fast, inexpensive alternative to traditional testing and monitoring techniques is desirable, since secretion of insulin and C-peptide is impaired in diabetes mellitus.. A highly sensitive immunoassay was developed for the simultaneous measurement of C-peptide and insulin levels in human serum, utilizing dual-label time-resolved fluoroimmunoassay (TRFIA) and magnetic particle technologies. This assay was characteristic for a single-step sandwich-type immunoassay, wherein antibody-coated magnetic particles were used as the solid phase and Eu(3+) and Sm(3+) chelate labels were used for detection.. Antibody-coated magnetic particles in a TRFIA format performed well in addressing a number of quantitative needs.. The results of this assay correlated well with commercial chemiluminescence assays and provided a number a advantages, including reduced sample volume, reduced reagent and personnel costs and reduced assay time, while maintaining the required clinical sensitivity.

Topics: Antibodies; C-Peptide; Calibration; Diabetes Mellitus; Fluoroimmunoassay; Glucagon; Humans; Insulin; Limit of Detection; Magnetic Phenomena; Reproducibility of Results; Sensitivity and Specificity; Time Factors

To characterize the clinical signature and etiopathogenetic factors of diabetes associated with pancreas disease [type 3 diabetes mellitus (T3cDM)]. To estimate incidence and identify predictors of both diabetes onset and remission after pancreatic surgery. A prospective observational study was conducted. From January 2008 to December 2012, patients (n = 651) with new diagnosis of pancreatic disease admitted to the Pancreatic Surgery Unit of the San Raffaele Scientific Institute were evaluated. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. At baseline, the prevalence of diabetes was 38 % (age of onset 64 ± 11 years). In most cases, diabetes occurred within 48 months from pancreatic disease diagnosis. Among different pancreatic diseases, minor differences were observed in diabetes characteristics, with the exception of the prevalence. Diabetes appeared associated with classical risk factors for type 2 diabetes (i.e., age, sex, family history of diabetes and body mass index), and both beta-cell dysfunction and insulin resistance appeared relevant determinants. The prevalence of adult-onset autoimmune diabetes was as previously reported within type 2 diabetes. Within a few days after surgery, either diabetes remission or new-onset diabetes was observed. In patients with pancreatic cancer, no difference in diabetes remission was observed after palliative or resective surgery. Classical risk factors for type 2 diabetes were associated with the onset of diabetes after surgery. T3cDM appeared as a heterogeneous entity strongly overlapped with type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Pancreatic Diseases; Prospective Studies; Young Adult

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus; Disasters; Disease Management; Earthquakes; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Japan; Male; Predictive Value of Tests; Retrospective Studies

Exhaled breath analysis is able to identify biomarkers of respiratory and systemic diseases. It was hypothesized that markers of pancreatic function would be identified in the breath of those with diabetes mellitus and cystic fibrosis. Children aged 6-18 years old with diabetes mellitus (DM), cystic fibrosis (CF), cystic fibrosis related diabetes (CFRD) and healthy controls (C) contributed exhaled breath condensate (EBC), with concurrent blood glucose measurements taken from a subset. EBC C-peptide, glucose, sodium concentrations and conductivity were subsequently measured.A total of 104 children were recruited (DM = 56, CF = 26, CFRD = 5, C = 17). C-peptide was detected in EBC: CF 19.6  ±  11.7 pmol L(-1); DM: 9.66  ±  8.27 pmol L(-1); CFRD: 11.9  ±  9.23 pmol L(-1) which was significantly higher than in the control group (0.987  ±  2.26 pmol L(-1)) (p < 0.0001). No statistically significant difference was seen between the three groups for glucose, conductivity or sodium concentration.Glucose was not reliably found in EBC, but C-peptide was found to be higher in CF EBC. This may represent inflammation and a change in airway integrity, rather than increased secretion of this peptide.

Topics: Adolescent; Analysis of Variance; Biomarkers; Blood Glucose; Breath Tests; C-Peptide; Case-Control Studies; Child; Cystic Fibrosis; Diabetes Mellitus; Electric Conductivity; Exhalation; Female; Humans; Ions; Male; Pancreas; Sodium

There is controversy regarding whether a specific hepatitis C virus (HCV) genotype is associated with diabetes mellitus. This study aimed to investigate HCV genotype distribution in diabetics and its relation to some clinical and laboratory variables in HCV-positive diabetic versus non-diabetic Egyptians in East Delta.. The study included 100 HCV-positive patients of which 66 were diabetic in addition to 35 healthy adults as a control group. Clinical assessment, laboratory measurements of plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α) and liver functions (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)) as well as HCV genotype determination were done, and AST/platelet ratio index (APRI) and Homoeostasis Model of Assessment-Insulin Resistance (HOMA-IR) were calculated.. The main results were the presence of HCV genotype 3, in 31.8% of the diabetic group and in 26.5% of the non-diabetic group, while the remainder of cases had genotype 4, the predominant genotype in Egypt. This is the first report of the presence of HCV genotype 3 in about 30% of an Egyptian cohort. However, there was no significant difference in genotype distribution between both groups. Further, there were significantly higher values of HOMA-IR, insulin and C-peptide in HCV-positive groups in comparison to the control group, while TNF-α was significantly higher in the HCV-positive diabetic group. However, there were no significant differences between both genotypes regarding these parameters.. Although this study reveals for the first time the presence of HCV genotype 3 in a significant percentage of a group of Egyptian patients, where the majority were diabetic, the association between diabetes and certain HCV genotypes could not be confirmed on the basis of our findings. Hence, taking into consideration the impact of such a finding on the treatment decisions of those patients, further studies are warranted to explore these findings to a greater extent.

Topics: Adult; Alanine Transaminase; Analysis of Variance; Aspartate Aminotransferases; Blood Glucose; C-Peptide; C-Reactive Protein; Diabetes Mellitus; Egypt; Female; gamma-Glutamyltransferase; Genotype; Hepacivirus; Hepatitis C; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; Platelet Count; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The diabetes mellitus Incidence Cohort Registry (DiMelli) aims to characterize diabetes phenotypes by immunologic, metabolic, and genetic markers. We classified patients into three groups according to islet autoantibody status and examined whether patients with multiple diabetes-associated autoantibodies, one autoantibody, or without autoantibodies differed with respect to clinical, metabolic, and genetic parameters, including an insulin sensitivity (IS) score based on waist, HbA1c, and triglycerides. We also assessed whether metabolic markers predicted the immune status.. As of June 2012, 630 patients in Bavaria, Germany, aged <20 years diagnosed with any type of diabetes within the preceding 6 months were registered in DiMelli. We compared the clinical and laboratory parameters between islet autoantibody status defined patient groups. Parameters showing the strongest associations were included in principal component analysis. Receiver operating characteristic curves were used to assess the ability of the IS Score to predict islet autoantibody status.. Patients with multiple islet autoantibodies, one autoantibody, or without autoantibodies were significantly different in terms of BMI percentile, weight loss before diagnosis, fasting C-peptide (all, P<0.001), and IS Score (P=0.034). However, principal component analysis revealed no distinct patterns according to autoantibody status. At the optimal IS Score cut-off for predicting islet autoantibody positivity (single compared to none), the specificity was 52.0% and the sensitivity was 86.8%. With respect to prediction of multiple autoantibodies (compared to none), specificity and sensitivity were slightly lower and in combination inferior to those obtained using the BMI percentile and fasting C-peptide.. The DiMelli study indicated that patients with and without islet autoantibodies differed with respect to metabolic and genetic markers but there was considerable overlap of phenotypes, and autoantibody status could not be predicted by these parameters. Thus, our results suggest that refined diabetes classification may require both immune and metabolic phenotyping.

Topics: Adolescent; Autoantibodies; Body Mass Index; C-Peptide; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus; Female; Humans; Incidence; Infant; Insulin Resistance; Islets of Langerhans; Male; Phenotype; Registries; Young Adult

Magnetic resonance (MR) techniques allow noninvasive fat quantification. We aimed to investigate the accuracy of MR imaging (MRI), MR spectroscopy (MRS) and histological techniques to detect early-onset liver steatosis in three rat phenotypes assigned to an experimental glucolipotoxic model or a control group.. This study was approved by the institutional committee for the protection of animals. Thirty-two rats (13 young Wistar, 6 old Wistar and 13 diabetic Goto-Kakizaki rats) fed a standard diet were assigned to a 72h intravenous infusion of glucose and Intralipid fat emulsion or a saline infusion. Plasma insulin levels were measured. Steatosis was quantified in ex vivo livers with gradient-recalled multi-echo MRI, MRS and histology as fat fractions (FF).. A significant correlation was found between multi-echo MRI-FF and MRS-FF (r=0.81, p<0.01) and a weaker correlation was found between histology and MRS-FF (r=0.60, p<0.01). MRS and MRI accurately distinguished young Wistar and Goto-Kakizaki rats receiving the glucose+Intralipid infusion from those receiving the saline control whereas histology did not. Significant correlations were found between MRI or MRS and insulin plasma level (r=0.63, p<0.01; r=0.57, p<0.01), and between MRI or MRS and C-peptide concentration (r=0.54, p<0.01; r=0.44, p<0.02).. Multi-echo MRI and MRS may be more sensitive to measure early-onset liver steatosis than histology in an experimental glucolipotoxic rat model.

Topics: Animals; C-Peptide; Diabetes Mellitus; Fat Emulsions, Intravenous; Fatty Liver; Glucose; Glucose Clamp Technique; Infusions, Intravenous; Insulin; Lipid Metabolism; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Rats; Rats, Wistar; ROC Curve; Tissue Fixation

The aim of the study was to analyse the prevalence and characteristics of secondary diabetes induced by 5-fluorouracil (5-FU) based chemotherapy in non-diabetic patients with colorectal cancer (CRC).. A total of 422 consecutive CRC patients who received 5-FU-based chemotherapy were retrospectively analysed. Fasting plasma glucose (FPG) levels were determined before each cycle of chemotherapy during active treatment and regular follow-up. The prevalence and characteristics of secondary hyperglycaemia were investigated, with special focus on the clinical outcome.. Among the 422 CRC patients, 60 had pre-existing hyperglycaemia. In the remaining 362 with normal FPG levels before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and impaired fasting glucose during the study period. Among the 42 secondary diabetic patients, 22 (52.4%) received anti-diabetes drug therapy, in 7 (16.7%) cases the FPG level returned to normal without any active intervention, and 13 (30.9%) cases received diet control and physiotherapy. Thirty-one (8.6%) patients developed diabetes. Based on the Common Terminology Criteria for Adverse Events, an adverse event over Grade 3 occurred in seven cases during follow-up. Diabetes-related adverse events had a serious negative impact on chemotherapy in six cases. Diabetes-related death occurred in three patients.. Secondary diabetes associated with 5-FU-based chemotherapy occurs in around 10% of CRC patients, with a significant negative impact on treatment and clinical outcome. 5-FU-related diabetes should be regarded as a common side effect of 5-FU treatment.

Topics: Aged; Analysis of Variance; Antimetabolites, Antineoplastic; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus; Feeding Behavior; Female; Fluorouracil; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Physical Therapy Modalities; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome

The aim of this study was to examine whether autoantibodies to: ZnT8-Tryptophan (ZnT8WA), ZnT8-Arginine (ZnT8RA) or ZnT8-Glutamine (ZnT8QA) correlated with C-peptide or other autoantibodies and to assess diagnostic sensitivity of ZnT8WRQA. Specimens from 270 newly diagnosed diabetic subjects (age 15-34 years) and after 5 years duration of disease were examined. Four linear regression models were used to dissect the importance of different factors from diagnosis for the respective difference of (logZnT8WA), (logZnT8RA) and (logZnT8QA); A) unadjusted model for: initial C-peptide, age, BMI, gender, clinical classification, ICA, GADA, IA-2A, (ZnT8WA/ZnT8RA/ZnT8QA); B) C-peptide corrected for clinical factors; C) C-peptide corrected for autoantibodies; D) C-peptide corrected for all factors. The least decrease of ZnT8WA was observed in patients with high initial C-peptide in all models A) p = 0.054; B) p = 0.021; C) p = 0.047 and D) p = 0.017. A less statistically significant decrease of ZnT8RA was observed in patients with high initial C-peptide in A) p = 0.038 and C) p = 0.047, but this finding was not confirmed in B or D. The decrease of ZnT8QA levels was not related to C-peptide in any model but correlated to age D) p = 0.049. Furthermore, patients with unclassifiable diabetes showed the least decrease in D) p = 0.035. ZnT8WA, ZnT8RA or ZnT8QA were identified as a single autoantibody in 3.8% (10/266) of patients, thereby increasing diagnostic sensitivity from 79.3% (211/266) to 83.1% (221/266). In conclusion, high initial C-peptide was the most important factor even after adjusting for other factors in patients positive for ZnT8WA or ZnT8RA to remain autoantibody positive 5 years after diagnosis.

Topics: Adolescent; Adult; C-Peptide; Cation Transport Proteins; Diabetes Mellitus; Female; Humans; Insulin-Secreting Cells; Linear Models; Male; Prospective Studies; Radioimmunoassay; ROC Curve; Sweden; Young Adult; Zinc Transporter 8

To reveal the specific features of pancreatogenic diabetes mellitus (DM) and to discuss the principles of its medical therapy.. Sixty-six patients (55 men and 11 women) aged 30 to 65 years with chronic pancreatitis (CP) were examined. The disease was accompanied with pancreatic calcification and cyst formation in 22 and 13 patients, respectively; 5 patients were found to have a pseudotumorous form of CP and 10 had clinically and laboratorily verified DM. 14 resections and 11 drainages for complicated CP were performed. Its diagnosis was established on the basis of clinical, instrumental, and laboratory findings. Pancreatic exocrine function was evaluated from the results of the 13C-trioctanain breath test (BT) that is designed for its in vivo diagnosis. The level of C-peptide was studied by an enzyme immunoassay.. The findings suggest that pancreatic exocrine function is diminished in CP patients both with and without complications as compared with the normal value in 44% (24.3 +/- 1.7 and 26.6 +/- 1.3%, respectively), as shown by BT. According to the results of BT, a substantial decrease in the total proportion of a released label was noted in patients with CP and pancreatic calcification, diabetes mellitus, after resection operations for complications of CP and there were also significant differences, as compared to a group of CP patients without complications. In these patient groups, the level of C-peptide fell to a larger extent than that in CP patients without complications and in patients with CP and DM it was decreased to 0.11 +/- 0.02 ng/ml, the normal level being 0.7-1.9 ng/ml. There was a direct correlation between C-peptide levels and BT results in the patients with CP after resection operations. Insulin antibodies were absent in all the examined patients with CP, which proves the specific type of DM in CP. These are detectable only in type 1 DM. Seven patients with CP and DM were found to have calcification, 5 underwent resection operations, 3 had calcification and underwent pancreatic resection operations.. The development of DM may be predicted in CP patients with formation of pancreatic calcification and resections. In these patients, pancreatic exocrine dysfunction achieves a severe degree.

Topics: Adult; Breath Tests; C-Peptide; Calcinosis; Diabetes Mellitus; Female; Glucose; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Pancreatitis, Chronic

No data is so far available on the relation between glucose values and insulin resistance and mortality, both at short- and long-term, in patients with acute heart failure syndromes (AHF). We prospectively assessed in 100 consecutive non-diabetic AHF patients whether acute glucose metabolism, as indicated by fasting glycemia and insulin resistance (HOMA index) was able to affect short- and long-term mortality. In the overall population, 51 patients showed admission glucose values >140 mg/dl. No significant difference was observed in admission and peak glycemia, insulin and C-peptide values and in HOMA-index between dead and survived patients. At multivariate logistic backward stepwise analysis the following variables were independent predictors for in-ICCU mortality (when adjusted for left ventricular ejection fraction): Fibrinogen (1 mg/dl increase) [OR (95% CI) 0.991 (0.984-0.997); p = 0.004]; NT-pro BNP (100 UI increase) [OR (95%CI) 1.005 (1.002-1.009); p = 0.004]; leukocyte count (1,000/μl increase) [OR (95%CI) 1.252 (1.070-1.464); p = 0.005]. eGFR was independently correlated with long-term mortality (HR 0.96, 95%CI 0.94-0.98, p < 0.001). In consecutive patients with acute heart failure without previously known diabetes, we documented, for the first time, that fasting glucose and insulin values and insulin resistance do not affect mortality at short- and long-term. Inflammatory activation (as indicated by the leukocyte count and the fibrinogen) and NT-pro BNP levels are independent predictors for early death while the eGFR affects the long-term mortality.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperglycemia; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

To report C-peptide results in newly diagnosed patients and the relation to clinical diagnosis of diabetes.. A nation-wide cohort, the Better Diabetes Diagnosis study was used to determine serum C-peptide at diagnosis in 2734 children and adolescents. Clinical data were collected at diagnosis and follow-up. C-peptide was determined in a validated and controlled time-resolved fluoroimmunoassay.. The clinical classification of diabetes, before any information on human leukocyte antigen, islet autoantibodies, or C-peptide was received, was type 1 diabetes (T1D) in 93%, type 2 diabetes (T2D) in 1.9%, maturity onset diabetes of the young (MODY) in 0.8%, secondary diabetes (0.6%), while 3.3% could not be classified. In a random, non-fasting serum sample at diagnosis, 56% of the patients had a C-peptide value >0.2 nmol/L. Children classified as T2D had the highest mean C-peptide (1.83 + 1.23 nmol/L) followed by MODY (1.04 ± 0.71 nmol/L) and T1D (0.28 ± 0.25 nmol/L). Only 1/1037 children who had C-peptide <0.2 nmol/L at diagnosis was classified with a type of diabetes other than T1D. Predictive value of C-peptide >1.0 nmol/L for the classification of either T2D or MODY was 0.46 [confidence interval 0.37-0.58].. More than half of children with newly diagnosed diabetes have clinically important residual beta-cell function. As the clinical diagnosis is not always straightforward, a random C-peptide taken at diagnosis may help to classify diabetes. There is an obvious use for C-peptide determinations to evaluate beta-cell function in children with diabetes.

Topics: Adolescent; Age of Onset; C-Peptide; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnostic Techniques, Endocrine; Female; Humans; Infant; Infant, Newborn; Male; Osmolar Concentration; Predictive Value of Tests

Glucose homeostasis is significantly altered immediately after partial pancreatectomy. The present study examined the long-term consequences of a hemipancreatectomy in 10 patients with chronic pancreatitis and 10 patients with benign pancreatic and extrapancreatic tumors. A 240-minute oral glucose challenge was performed before and shortly after pancreatic surgery, as well as after a follow-up of 3.1 ± 0.5 years. Plasma concentrations of glucose, insulin, and C-peptide were determined; and indices of insulin sensitivity and insulin secretion were calculated. In both groups of patients, fasting and postchallenge glucose concentrations were significantly altered immediately after surgery, but returned to preoperative levels at the time of follow-up (P < .0001). Postchallenge insulin and C-peptide concentrations were reduced immediately after surgery (P < .0001), but were partly normalized at the time of follow-up (P < .0001). These changes were not accompanied by improvements in insulin sensitivity (Matsuda index). However, the oral disposition index revealed a significant recovery of β-cell function at the time of follow-up (P < .05). These findings demonstrate a capacity for recovery of glucose control after partial pancreatectomy and suggest that β-cell function can improve significantly over time even in adult humans.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis, Chronic; Recovery of Function

Heterozygous male Munich Ins2(C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in male Munich Ins2(C95S) mutants.. One group of male Ins2(C95S) mutants was treated with subcutaneous insulin pellets, as soon as blood glucose levels began to rise; placebo-treated mutants and wild-type mice served as controls. An additional group of mutant mice received a sodium-dependent glucose transporter 2 (SGLT2) inhibitor (AVE2268) via rodent chow.. Insulin treatment normalised blood glucose concentrations, improved oral glucose tolerance, preserved insulin sensitivity and inhibited oxidative stress of Munich Ins2(C95S) mutant mice. Pancreatic C-peptide content, as well as total beta cell and isolated beta cell volumes, of insulin-treated mutant mice were higher than those of placebo-treated mutants. In addition, alpha cell dysfunction and hyperplasia of non-beta cells were completely normalised in insulin-treated mutant mice. Treatment with the SGLT2 inhibitor lowered blood glucose, improved glucose tolerance and normalised insulin sensitivity as well as oxidative stress of Ins2(C95S) mutants. The abundance of the endoplasmic reticulum (ER) stress markers binding Ig protein (BiP) and phosphorylated eukaryotic translation initiation factor 2 alpha (P-eIF2α) was significantly increased in the islets of mutants, before onset of hyperglycaemia, vs wild-type mice.. We conclude that early insulin treatment protects Munich Ins2(C95S) mutant mice from insulin resistance, alpha cell hyperfunction, beta cell loss and hyperplasia of non-beta cells, some well-known features of human diabetes mellitus. Therefore, insulin treatment may be considered early for human patients harbouring INS mutations.

Topics: Animals; Animals, Newborn; C-Peptide; Diabetes Mellitus; Disease Models, Animal; Endoplasmic Reticulum; Glucose; Homeostasis; Insulin; Insulin-Secreting Cells; Male; Mice; Oxidative Stress; Pancreas; Phenotype; Placebos; Sodium-Glucose Transporter 2

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.

Topics: Adult; C-Peptide; Comorbidity; Cystic Fibrosis; Diabetes Mellitus; Disease Progression; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Postprandial Period; Young Adult

This edition of 'Then and now' re-examines Lise Heding's very highly cited paper 'Radioimmunological determination of human C-peptide in serum', which was published in Diabetologia in 1975. We show how this article and other related articles by Heding contributed to heightened respect for C-peptide (and transformation of Heding's research programme). Initially thought of as an inert discard, C-peptide in blood is now recognised as an excellent surrogate measure of insulin secretion under a wide range of conditions. The assay is especially valuable for acute ascertainment of the insulin secretory capabilities of patients with type 1 diabetes or of transplanted beta cells. The assay is also being used to monitor endogenous beta cell loss or in vivo expansion of beta cell mass over the long term. We conclude with two promising future applications: (1) measurements of C-peptide in blood (along with insulin, glucose, and HbA(1c)) at annual intervals as a potential approach to earlier diagnosis of diabetes; and (2) among many recent advances in recognising properties of C-peptide (including status as a candidate hormone), most promising is C-peptide as a possible therapy for diabetic neuropathy and nephropathy.

Topics: C-Peptide; Diabetes Mellitus; Humans; Immunoassay; Insulin

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI(0,120)) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI(0,120) and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients.

Topics: Acromegaly; Adult; Asian People; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Prediabetic State; Republic of Korea

Institut Georges Lopez-1 (IGL-1) is a preservation solution similar to University of Wisconsin (UW) with reversed Na/K contents. In this study, we assessed the impact of IGL-1, UW, and Celsior (CS) solutions on islet isolation and transplant outcome.. We retrospectively analyzed 376 islet isolations from pancreases flushed and transported with IGL-1 (n=95), UW (n=204), or CS (n=77). We determined isolation outcome and β-cell function in vitro. Transplanted patients were divided into three groups depending on preservation solution of pancreas, and islet graft function was assessed by decrease in daily insulin needs, C-peptide/glucose ratios, β-scores, and transplant estimated function at 1- and 6-month follow-up.. IGL-1, UW, and CS groups were similar according to donor age, body mass index, and pancreas weight. There was no difference in islet yields between the three groups. Success rates, transplant rates, β-cell secretory function, and viability were similar for all three groups. We observed no difference in decreased insulin needs, C-peptide glucose ratios, β-scores, and transplant estimated function at 1- and 6-month follow-up between IGL-1, UW, and CS groups.. Our study shows that IGL-1 is equivalent to UW or CS solutions for pancreas perfusion and cold storage before islet isolation and transplantation.

Topics: Adenosine; Adult; Allopurinol; Analysis of Variance; Biomarkers; Blood Glucose; C-Peptide; Chi-Square Distribution; Diabetes Mellitus; Disaccharides; Electrolytes; Female; Glutamates; Glutathione; Glycated Hemoglobin; Histidine; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Mannitol; Middle Aged; Organ Preservation; Organ Preservation Solutions; Raffinose; Retrospective Studies; Time Factors; Tissue and Organ Harvesting; Tissue Culture Techniques; Treatment Outcome

Periampullary malignant neoplasms have been increasing in Japan, mainly in response to an increase in the incidences of pancreatic cancer, and glucose intolerance due to deterioration of insulin secretion is an important problem. We investigated preoperative parameters to predict postoperative insulin secretion and the need for insulin therapy in patients undergoing pancreaticoduodenectomy (PD). Thirty-six patients with malignant neoplasms of periampullary lesions were enrolled. Preoperative pancreatic parenchymal thickness was evaluated by computed tomography. Insulin secretion and glucose tolerance were evaluated by a 75-g oral glucose tolerance test and an intravenous glucagon loading test. The relationships between postoperative insulin secretion and preoperative parameters and the cut-off values for predicting the need for postoperative insulin therapy for glycemic control were investigated. Pancreatic parenchymal thickness and other preoperative parameters, including the increment of serum C-peptide (Δ C-peptide), fasting plasma C-peptide (F-CPR), insulinogenic index (I.I.) and fasting plasma glucose (FPG), were significantly associated with postoperative insulin secretion. Multiple regression analyses revealed that preoperative Δ C-peptide or F-CPR was the most significant determinant of postoperative insulin secretion, followed by pancreatic parenchymal thickness. In the receiver operating characteristic curve, the best preoperative cut-off values for predicting the need for postoperative insulin therapy were a Δ C-peptide of 0.65 ng/mL, a F-CPR of 0.85 ng/mL and a pancreatic parenchymal thickness of 6.0 mm. Both preoperative insulin secretion and pancreatic parenchymal thickness effectively predict postoperative insulin secretion and identify subjects who need postoperative insulin therapy for glycemic control.

Topics: Abdominal Neoplasms; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Organ Sparing Treatments; Pancreas; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Preoperative Period; Prognosis; ROC Curve; Tomography, X-Ray Computed

C-peptide is a main outcome measure in treatment trials of diabetes. C-peptide also has a role in the classification of diabetes, which is often difficult in adults and this is also increasingly recognised in adolescents and elders.. We aimed to describe the levels of C-peptide in relation to age and body mass index (BMI) in a large population-based cohort of adults with newly diagnosed diabetes and compare the capabilities of C-peptide, age and BMI to discriminate between autoimmune and non-autoimmune diabetes.. Blood samples from 1180 patients were analysed regarding islet cell antibody, glutamic acid decarboxylase antibody and fasting C-peptide (FCP). Receiver operating characteristics (ROC) curves were analysed to check the ability of age, BMI and C-peptide to discriminate between autoantibody-positive (Ab(+)) and -negative (Ab(-)) diabetes.. Mean FCP was 0.73±0.5 (range 0.13-1.80) nmol/l in the Ab(+) and 1.42±0.9 (range 0.13-8.30) nmol/l in the Ab(-). FCP was 0.02 nmol/l higher per year increase in age at diagnosis of diabetes. Mean BMI was 26.0±4.8 (range 18.0-39.0) kg/m(2) in the Ab(+) and 28.9±5.3 (range 15.5-62.6) kg/m(2) in the Ab(-). FCP increased with age also within each BMI group. The highest area under the curve (AUC) in the ROC analysis was found for C-peptide, followed by age and BMI (0.78, 0.68 and 0.66 respectively).. At diagnosis of diabetes, C-peptide was superior to age and BMI in discriminating between autoimmune and non-autoimmune diabetes. C-peptide increased significantly with BMI and age, latter also within each BMI group. Most of the adults had normal or high levels of C-peptide at presentation of diabetes among the autoimmune patients.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Analysis of Variance; Area Under Curve; Autoantibodies; Autoimmunity; Biomarkers; Body Mass Index; C-Peptide; Carboxy-Lyases; Diabetes Mellitus; Diagnosis, Differential; Fasting; Female; Glutamic Acid; Humans; Incidence; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; ROC Curve; Statistics, Nonparametric; Sweden

Juvenile (2-23 years old) cynomolgus monkeys are frequently used as recipients in non-human primate islet transplantation studies. The aim of this study was to examine the effects of different doses of streptozotocin (STZ), and find the optimal dose for inducing diabetes in these monkeys. Fifteen juvenile (2-3 years old) cynomolgus monkeys were separated into three groups and administered with different doses of STZ (100, 68 or 60 mg kg(-1)). Basal and glucose-stimulated blood glucose, insulin, and C-peptide levels, as well as body weights were monitored. Hepatic and renal function tests and pancreatic immunohistochemistry were performed before and after STZ treatment. Monkeys treated with both 100 and 68 mg kg(-1) of STZ exhibited continuous hyperglycemia, which coincided with a nearly complete loss of islet β-cells. Two monkeys received 60 mg kg(-1) of STZ, but only one became completely diabetic. During the first week following STZ treatment, hepatic and renal function slightly increased in these three groups. However, 24 hours post-STZ, serum total bile acid levels were significantly increased in monkeys treated with 100 mg kg(-1) than those treated with 68 mg kg(-1) of STZ (P<0.05). These data suggest that 100 mg kg(-1) and 68 mg kg(-1) of STZ can safely induce diabetes in cynomolgus monkeys aged 2-3 years, but 68 mg kg(-1) of STZ, rather than 100 mg kg(-1) of STZ, may be more appropriate for inducing diabetes in these monkeys. Furthermore, body surface area, rather than body weight, was a more reliable determinant of dosage, where 700 mg m(-2) of STZ should be the lower limit for inducing diabetes in juvenile monkeys.

Topics: Animals; Bile Acids and Salts; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperglycemia; Immunohistochemistry; Islets of Langerhans; Kidney; Liver; Macaca fascicularis; Male; Streptozocin; Time Factors

Blood glucose variability is known to be associated with increased risk of long-term complications. Reliable indices for predicting hyperglycaemic and hypoglycaemic fluctuations are therefore needed. Glycaemic standard deviation (SD) obtained by continuous glucose monitoring correlates closely with nine previously described glycaemic variability formulas. Here, new indices predictive of glycaemic variability were developed, which can be calculated from laboratory measures based on a single blood draw. The indices included the glycated albumin (GA) to HbA1c ratio (GA/A1c ratio) and the fasting C-peptide immunoreactivity (FCPR) to fasting plasma glucose (FPG) ratio (FCPR index). Predictive values of these indices were assessed in 100 adults with diabetes. GA/A1c ratio and FCPR index showed close associations with glycaemic SD in addition to the nine existing glucose variability formulas. Subjects with a GA/A1c ratio ≥ 2.8 and FCPR index <3.0 showed the greatest SD and longest durations of hypoglycaemia, while those with a GA/A1c ratio <2.8 and FCPR index ≥ 3.0 had smaller SDs and little sign of hypoglycaemia. In adults with diabetes, a high GA/A1c ratio and low FCPR index value reflect higher glycaemic excursions, irrespective of diabetes type. Simultaneous measurements of GA, HbA1c, FPG and FCPR may help to identify a group of patients who warrant closer monitoring in relation to glycaemic variability and hypoglycaemia.

Topics: Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Reference Values; ROC Curve; Serum Albumin

Insulin resistance, characterized by hyperinsulinemia and normal or elevated serum glucose, is an established precursor to diabetes and cardiovascular disease. Despite fasting serum C-peptide levels being an accurate and stable marker of endogenous insulin production used in patients with diabetes, it is unknown whether C-peptide could serve as a marker of insulin resistance and predict outcomes in patients without diabetes.. This is a retrospective cohort study using data from the NHANES-3 (1988-1994) survey with mortality follow-up through December 31, 2006. Participants included 5153 subjects, 40 to 74 years of age with fasting glucose ≥ 70 mg/dL, without diabetes by history or laboratory testing. Receiver-operating-curve analysis compared fasting C-peptide against known insulin resistance measures such as fasting plasma glucose, serum insulin, HOMA-IR, quantitative-insulin-sensitivity-check-index, and metabolic syndrome for the prediction of cardiovascular and overall death. Subjects were then stratified by quartiles of C-peptide levels. Cox proportional-hazards modeling compared hazards of cardiovascular and overall death amongst C-peptide quartiles and adjusted for potential confounders of cardiovascular and diabetes risk. Fasting serum C-peptide levels predicted cardiovascular and overall death better than other studied measures (AUC=0.62 and 0.60 respectively vs the rest, with AUC ≤ 0.58 and ≤ 0.57 respectively, P<0.001). When compared with the lowest C-peptide quartile, subjects in the highest quartile had significantly higher adjusted hazard ratios (HR) of cardiovascular death (HR=1.60, 95%CI 1.07 to 2.39) and overall mortality (HR=1.72, 95%CI 1.34 to 2.21) after controlling for confounders.. C-peptide levels significantly related to hazards of cardiovascular and overall death in nondiabetic adults and was a better predictor of these outcomes than serum insulin and/or glucose derived measures.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Fasting; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Mortality; Nutrition Surveys; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; ROC Curve

Recent studies in mice have demonstrated that insulin signaling in osteoblasts stimulates bone formation and reduces osteoprotegerin production; the latter results in an increase in bone resorption, which then leads to the release of undercarboxylated osteocalcin from bone. Undercarboxylated osteocalcin, in turn, enhances insulin sensitivity.. The objective of the study was to test whether physiological changes in insulin levels regulate bone metabolism in humans.. This investigation was an analysis of samples from a prospective study.. The study was conducted at a clinical research unit.. Fourteen subjects underwent a 7-h stepped insulin infusion accompanied by a glucose clamp and somatostatin infusion along with replacement infusions of GH and glucagon, thus isolating possible effects of insulin on bone. Insulin was infused at rates achieving low (∼150 pmol/liter), intermediate (∼350 pmol/liter), or high (∼700 pmol/liter) plasma insulin levels.. Bone turnover markers, undercarboxylated osteocalcin, and osteoprotegerin levels at the end of the low, intermediate, and high dose insulin infusions were measured.. Values for the outcome measures at the end of the intermediate- and high-dose insulin infusions were no different from values at the end of the low-dose insulin infusion. However, measures of insulin sensitivity (glucose infusion and disappearance rates) correlated positively with C-terminal telopeptide of type I collagen levels.. Acute changes in insulin levels, as occur during meals, do not regulate bone turnover, undercarboxylated osteocalcin, or osteoprotegerin levels. However, the correlation of measures of insulin sensitivity with bone resorption suggests the need for further studies in humans on the possible regulation of bone metabolism by insulin.

Topics: Absorptiometry, Photon; Biomarkers; Blood Glucose; Bone and Bones; C-Peptide; Diabetes Mellitus; Endpoint Determination; Female; Glucagon; Glucose Clamp Technique; Human Growth Hormone; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Peptide Fragments; Procollagen; Prospective Studies

To explore whether it is possible to predict a child's eventual diabetes phenotype using characteristics at initial presentation, we reassessed 111 young patients on average 7.8 ± 4.2 (2.2-19.7) [mean ± SD (range)] years after diagnosis.. Medical records at diagnosis for 111 patients, aged 0-17, were compared with their follow-up characteristics including stimulated C-peptide (CP) and islet autoantibodies (AB).. Initially, 18 patients were obese; 9 displayed other type 2 diabetes (T2DM) features (polycystic ovary syndrome, acanthosis, diagnosed T2DM); the remaining 84 had a classic type 1 diabetes (T1DM) presentation. At follow-up, 83 patients (75%) with no measured CP were classified as T1DM; 17 (15%) were CP+ and AB- and thus considered T2DM. Eleven patients with both T1DM and T2DM features were classified as having mixed diabetes phenotype (MDM). One-fifth (22 subjects) changed presumed phenotype at follow-up. In multivariable models, T1DM patients were younger at diagnosis, had higher initial glucose values, were more likely to have experienced ketoacidosis, and less likely to be obese or of African American ethnicity.. Ten percent of subjects had MDM and 15% had T2DM at ∼8 years' duration. Although no onset feature was completely reliable, ketoacidosis and hyperglycemia were more likely to predict T1DM; obesity and African American ethnicity made T2DM more likely. At diagnosis, features of T2DM in addition to obesity were strongly predictive of eventual T2DM phenotype. Given the significant percentage who changed or had mixed phenotype, careful tracking of all young people with diabetes is essential to correctly determine eventual disease type.

Topics: Adolescent; Adult; Autoantibodies; Black or African American; C-Peptide; Chicago; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Longitudinal Studies; Male; Obesity; Phenotype

Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.. To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.. A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.. Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.. The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male

Fabrication of a glucose biosensor based on Au-cluster emission quenching in the UV region is reported. The glucose biosensor is highly sensitive to β-d-glucose in 2.5-25.0mM range as confirmed from a linear calibration plot between Au-cluster colloid emission intensity as a function of β-d-glucose concentration. The interaction of β-d-glucose with l-cysteine capped Au cluster colloids has been confirmed from their Fourier transformed infrared spectroscopy (FTIR) measurements. It has been found that the biomolecules present in the serum such as ascorbic and uric acids, proteins and peptides do not interfere and affect in glucose estimation as confirmed from their absorption and fluorescence (FL) emission measurements. Practical utility of this sensor based on FL quenching method has been demonstrated by estimating the glucose level in human serum that includes diabetes and the data were found to be comparable or more accurate than those of the pathological data obtained from a local hospital. In addition, this biosensor is useful to detect glucose level over a wide range with sensor response time of the order of nano to picoseconds that is emission lifetime of Au clusters.

Topics: Animals; Biosensing Techniques; Blood Glucose; C-Peptide; Cattle; Colloids; Cysteine; Diabetes Mellitus; Gold; Humans; Metal Nanoparticles; Serum Albumin, Bovine; Spectrometry, Fluorescence; Spectrophotometry; Spectroscopy, Fourier Transform Infrared

C-peptide is cleaved from the proinsulin chains A and B during insulin synthesis. The views on its role in human physiology has changed in recent years. Soon after discovery of C-peptide it was believed that this protein is inactive by-product of insulin synthesis, and its role is limited to role in conformational changes of insulin and indicator of exocrine function of the pancreas. At present, it is known that C-peptide is bioactive compound, with multiple functions, and it acts probably through membrane receptor. The known physiological actions of C-peptide are related mainly to kidneys, circulatory and nervous systems function. In kidney, it changes the glomerular filtration and proteinuria. In blood vessels, C-peptide is able to act as a vasodilator. It is also able to improve the neurotransmission rate. The newest data indicates possible involvement of C-peptide in etiopathology of diabetes and polycystic ovary syndrome. The possible role of C-peptide in these disorders is very interesting and requires further studies.

Topics: C-Peptide; Diabetes Mellitus; Endocrine System Diseases; Female; Glomerular Filtration Rate; Humans; Insulin; Pancreas; Polycystic Ovary Syndrome; Proinsulin; Vasodilation

Assessing the engrafted islet mass is important in evaluating the efficacy of islet transplantation. We previously demonstrated that the average secretory unit of islet transplant objects (SUITO) index within 1 month of allogeneic islet transplantation was an excellent predictor of insulin independence. However, the usefulness of the SUITO index for evaluating autologous islet transplantation has not been explored. The purpose of the present study was to assess the relationship between the SUITO index and clinical outcomes after total pancreatectomy followed by autologous islet transplantation.. We performed 27 total pancreatectomies followed by autologous islet transplantation from October 2006 to January 2011. Cases were divided into an insulin-independent group (IIG; n = 12) and an insulin-dependent group (lDG; n = 15). The SUITO index was calculated by the formula [fasting C-peptide (ng/mL)/fasting glucose (mg/dL) -63] × 1,500. The average SUITO index within the first month of transplantation except for days 0, 1, and 2, maximum SUITO index, and most recent SUITO index were calculated in each case, and values were compared between the IIG and the IDG.. The average SUITO index within 1 month was significantly higher in the IIG than in the IDG (24.6 ± 3.4 vs 14.9 ± 2.0, respectively; P < .02). The maximum SUITO indices were 45.7 ± 7.7 in the IIG and 30.1 ± 8.1 in the IDG (not significant), and the recent SUITO indices were 36.9 ± 6.7 in the IIG and 22.8 ± 6.1 in the IDG (not significant).. The average SUITO index within 1 month was an excellent predictor of insulin independence after total pancreatectomy followed by autologous islet transplantation.

Topics: Adult; Blood Glucose; C-Peptide; Cell Survival; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Sex Factors; Time Factors; Transplantation, Autologous; Treatment Outcome

In order to identify features of the course pancreatic diabetes and discussion of the principles of conservative therapy were examined 66 patients with CP in age of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed with formation of calcification of pancreas, 13 - pancreatic cysts, and 5 revealed pseudo tumor form of CP, 10 patients had clinical and laboratory evidence of diabetes. Concerning CP complicated course were performed 14 resection and 11 draining operations on the pancreas. Based on clinical, instrumental and laboratory data was made the diagnosis of CP. Exocrine pancreatic function was assessed on the results of the breath test, using 13C-trioktanaine, which is applied for exocrine pancreatic function in vivo test. The content of C-peptide was investigated by enzyme-linked immunosorbent assay (ELISA). The data indicate pancreatic exocrine function decrease in patients with CP with complications and without complications in compare with the norm of 44% (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test. Significant decrease of the cumulative output tags based on the test data of patients with CP and pancreatic calcification, diabetes mellitus, after resection surgery with CP complications, and there were significant differences in compare with a group of patients with CP without complications (p = 0.5). The level of C-peptide in these groups of patients decreased significantly in compare with a group of patients with CP without complications, and patients with CP and Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie below the minimum values of norm. Obtained a direct correlation between the level of C-peptide and indicators breath test in patients after resection HP (r = 0,84, p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were negative, which proves the specific type of Diabetes at HP. Antibodies to insulin can be detected only at diabetes type 1. In 7 patients with CP and CD detected calcification, 5 patients performed resection surgery, 3 patients had calcification and conducted the pancreas resection. Thus, we can conclude that in patients with CP and formation of pancreas calcification, pancreas resections may predict the development of diabetes.

Topics: Adult; Aged; Blood Glucose; Breath Tests; C-Peptide; Diabetes Mellitus; Female; Gastrointestinal Agents; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Pancreatic Function Tests; Pancreatin; Pancreatitis, Chronic

Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. In this study, the human Pdx1 gene was transduced and expressed in murine adipose tissue-derived stem cells (ASCs). To evaluate pancreatic repair, we used a mouse model of pancreatic damage resulting in hyperglycemia, which involves injection of mice with streptozotocin (STZ). STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. These results suggest that Pdx1-ASCs are stably engrafted in the pancreas, acquire a functional beta-cell phenotype, and partially restore pancreatic function in vivo. The ease and safety associated with extirpating high numbers of cells from adipose tissues support the applicability of this system to developing a new cell therapy for IDDM.

Topics: Adipose Tissue; Animals; C-Peptide; Cell Differentiation; Diabetes Mellitus; Diabetes Mellitus, Type 1; Homeodomain Proteins; Humans; Hyperglycemia; Insulin; Insulin-Secreting Cells; Mice; Pancreas; Stem Cell Transplantation; Stem Cells; Streptozocin; Trans-Activators

It has previously been shown that misfolded mutant Akita proinsulin in the endoplasmic reticulum engages directly in protein complexes either with nonmutant proinsulin or with "hProCpepGFP" (human proinsulin bearing emerald-GFP within the C-peptide), impairing the trafficking of these "bystander" proinsulin molecules (Liu, M., Hodish, I., Rhodes, C. J., and Arvan, P. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 15841-15846). Herein, we generated transgenic mice, which, in addition to expressing endogenous proinsulin, exhibit beta-cell-specific expression of hProCpepGFP via the Ins1 promoter. In these mice, hProCpepGFP protein levels are physiologically regulated, and hProCpepGFP is packaged and processed to CpepGFP that is co-stored in beta-secretory granules. Visualization of CpepGFP fluorescence provides a quantifiable measure of pancreatic islet insulin content that can be followed in live animals in states of health and disease. We examined loss of pancreatic insulin in hProCpepGFP transgenic mice mated to Akita mice that develop neonatal diabetes because of the expression of misfolded proinsulin. Loss of bystander insulin in Akita animals is detected initially as a block in CpepGFP/insulin production with intracellular accumulation of the precursor, followed ultimately by loss of pancreatic beta-cells. The data support that misfolded proinsulin perturbs bystander proinsulin in the endoplasmic reticulum, leading to beta-cell failure.

Topics: Animals; Animals, Newborn; Bystander Effect; C-Peptide; Crosses, Genetic; Diabetes Mellitus; Female; Fluorescence; Glucose; Green Fluorescent Proteins; Homeostasis; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Mice; Mice, Transgenic; Organ Specificity; Proinsulin; Protein Folding; Rats; Secretory Pathway; Transgenes

The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients.. Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 years and in 21 matched healthy volunteers (HVs). Insulin and C-peptide responses were measured during the first (5-10 min) and second (120-150 min) release phase, and after glucagon injection (150-160 min). Clamp-induced C-peptide release was compared with C-peptide release during OGTT.. Seven (41%) FDRs developed diabetes 3-63 months after their initial clamp test. In all phases they had lower C-peptide responses than non-progressors (p < 0.05) and HVs (p < 0.002). All five FDRs with low first-phase release also had low second-phase release and developed diabetes 3-21 months later. Two of seven FDRs with normal first-phase but low second-phase release developed diabetes after 34 and 63 months, respectively. None of the five FDRs with normal C-peptide responses in all test phases has developed diabetes so far (follow-up 56 to 99 months). OGTT-induced C-peptide release also tended to be lower in progressors than in non-progressors or HVs, but there was less overlap in results between progressors and the other groups using the clamp.. Clamp-derived functional variables stratify risk of diabetes in IA-2A(+) FDRs and may more consistently identify progressors than OGTT-derived variables. A low first-phase C-peptide response specifically predicts impending diabetes while a low second-phase response may reflect an earlier disease stage.. ClinicalTrials.gov NCT00654121. The insulin trial was financially supported by Novo Nordisk Pharma nv.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Family; Glucose Clamp Technique; HLA-DQ Antigens; Humans; Hyperglycemia; Insulin; Medical History Taking; Reference Values; Risk Assessment; Young Adult

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

We used homeostasis model assessment to investigate insulin sensitivity and secretion after a simultaneous pancreas-kidney transplant or kidney transplant alone. In that model, fasting plasma glucose and C-peptide levels are used to evaluate insulin sensitivity and beta-cell function.. Factors (eg, age, sex, race, delayed kidney allograft function) were correlated with homeostasis model assessment of beta-cell function and homeostasis model assessment of insulin sensitivity values after simultaneous pancreas-kidney transplant (n=89) or kidney transplant alone (n=68), and the results were compared with those in healthy subjects (n=49).. Homeostasis model assessment of beta-cell function values were similar in patients who underwent kidney transplant alone or a simultaneous pancreas-kidney transplant, and were higher than homeostasis model assessment of beta cell function values in healthy subjects. The homeostasis model assessment of insulin sensitivity showed intermediate values for patients who underwent a simultaneous pancreas-kidney transplant and correlated with prednisone dosages (in those who underwent kidney transplant alone) and tacrolimus levels (in patients who underwent a simultaneous pancreas-kidney transplant). Homeostasis model assessment of beta-cell function values correlated with prednisone dosages in both groups and with tacrolimus levels in only those who underwent a simultaneous pancreas-kidney transplant. The body mass index of subjects who underwent kidney transplant alone correlated with both homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. A family history of diabetes in subjects who underwent a simultaneous pancreas-kidney transplant correlated with homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results.. Immunosuppressive regimen and body mass index were linked with reduced insulin sensitivity after kidney transplant. A family history of diabetes was linked with higher values of insulin secretion and lower insulin sensitivity in patients who underwent a simultaneous pancreas-kidney transplant.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Homeostasis; Humans; Immunosuppressive Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Kidney Transplantation; Male; Models, Biological; Pancreas Transplantation; Pedigree; Prednisone; Tacrolimus

A 4-year-old girl was hospitalized in a local hospital with bloody diarrhoea, vomitus and abdominal pain. Because of acute abdominal symptoms she underwent appendectomy after which convulsions and acute respiratory distress were noticed. The child was transferred to the intensive care unit. During the examination she was unconscious, pale, oedematous with scattered ecchymoses, severe hypertension and urine output diminished to several ml per day. Routine blood tests showed microangiopathic anaemia, thrombocytopenia (52000/ul.) and uremia. Proteinuria and hematuria were revealed on urine examination. Among coagulation parameters kaolin-kefalin time (69 s) and D-dimers (2000-4000/ul.) were abnormal. On the strength of history, clinical and laboratory investigation the diagnosis of D-positive hemolytic uremic syndrome was established. Controlled artificial respiration (for 10 weeks), total parenteral alimentation (TPN), antihypertensive treatment and diuretics (furosemide, dopamine) were introduced. Daily temporary access hemodialyses were performed for 4 weeks. Subsequently peritoneal dialysis was started for 2 weeks. Despite the appropriate TPN glucose blood levels were unexpectedly high from first days from admission (200-330 mg%). Intensive intravenous insulin therapy was performed for 50 days. The child was discharged after 72 days with moderate renal function impairment (blood urea-53 mg%, creatinine-1,2 mg%), mild hypertension and proteinuria. Additional factor prone to thrombotic events was the 4G/4G genotype responsible for increased PAI-1 blood concentration, which may result in intensified fibrinolysis inhibition. Diabetes mellitus as a rare immunological complication of haemolytic uremic syndrome was suspected on the following evidence: positive anti-GAD antibodies (ELISA), elevated levels of glycosylated haemoglobin A1c, three-fold reduction of blood C-peptide concentration, negative family history for diabetes. After 12 y of follow up glucose and C-peptide concentrations were normal. Glucose loading test gave adequate response. Kidney function was decreased with serum creatinine 1.7-1.9 mg/dl and urea 60-75 mg/dl.

Topics: C-Peptide; Child, Preschool; Diabetes Mellitus; Female; Hemolytic-Uremic Syndrome; Humans; Renal Dialysis

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7-7.3]. Fasting (f)-insulin increased from 123 +/- 81 to 193 +/- 124 pmol/l (P = 0.03), whereas f-glucose was unchanged (6.0 +/- 0.8 vs. 6.2 +/- 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7-22%) and 53% (CI: 14-90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 +/- 1.82 vs. 4.85 +/- 2.37 mg.kg(-1).min(-1)) and glucose tracer-based rate of disappearance were unchanged (5.01 +/- 1.61 vs. 4.97 +/- 2.13 mg.kg(-1).min(-1)). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 +/- 0.42 vs. 2.42 +/- 0.58 mg.kg(-1).min(-1)) and was suppressed equally by insulin (1.1 +/- 0.1 vs. 1.0 +/- 0.1 mg.kg(-1).min(-1)). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.

Topics: Body Composition; C-Peptide; Diabetes Mellitus; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Liver; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Predictive Value of Tests; Rest

Cassia auriculata traditionally has been used to treat diabetes from ancient times. The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of C. auriculata (CLEt) in streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) rats. CLEt was orally administered to MD and SD rats at a dose of 400 mg/kg once a day for 15 days. CLEt-treated MD and SD rats showed significant reduction in fasting blood glucose. Assessment of plasma insulin and C-peptide following treatment with CLEt revealed significant elevation in their levels. Administration of CLEt enhanced the activity of hepatic hexokinase and phosphofructokinase and suppressed glucose-6-phosphatase and fructose-1,6-bisphosphatase in both MD and SD rats. A significant rise in glycogen content was also observed in both liver and muscles of CLEt-fed MD and SD rats. Histopathological examination of pancreatic sections revealed increased number of islets and beta-cells in CLEt-treated MD as well as SD rats. The findings of the study suggest that the antidiabetic effect of CLEt could be due to its insulinogenic action. In addition, impaired glucose homeostasis was improved by feeding the extract through amelioration in the carbohydrate metabolic pathways. Thus, the extract may exert an antidiabetic effect through pancreatic as well as extrapancreatic action.

Topics: Animals; Blood Glucose; C-Peptide; Cassia; Diabetes Mellitus; Disease Models, Animal; Glucose; Glycogen; Humans; Hypoglycemic Agents; Insulin; Liver; Male; Muscle, Skeletal; Plant Extracts; Plant Leaves; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Streptozocin

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Eating; Homeostasis; Humans; Insulin; Insulin-Secreting Cells

In vitro labeling of pancreatic islets by iron nanoparticles enables their detection as hypoitnense spots on serial magnetic resonance (MR) images. We report the first results of a pilot trial aiming to test the feasibility and safety of this technique in humans.. Islets were labeled in culture with 5 μL/mL ferucarbotran for 6 to 48 hr and transplanted into the portal vein (12 infusions) in 8 C-peptide negative recipients. The liver area was examined the next day and 1, 4, and 24 weeks posttransplant using a 3T MR scanner.. In all recipients, significant C-peptide levels and near-normal HbA1c values were achieved with 50% to 80% insulin dose reduction. No side effects related to the labeling procedure were documented. Typically, a significant islet spot number decrease (on average 60%) was detected at week 1 with subsequent only slight decrease for up to 24 weeks. In two subjects with labeling period of less than 6 and 10 hr, only few islet spots were detected corresponding to poor islet visualization in phantoms labeled for the same period of time.. Pancreatic islets (PI) visualization was safe and successful in all recipients but was less efficient if labeling period was less than 16 hr. Significant decrease of islet spots occurred at week 1, suggesting early islet destruction or impaired engraftment. Afterward, the islet spot numbers remained stable for up to 24 weeks. Data show that MR detection of ferucarbotran-labeled islets enables their long-term noninvasive visualization and correlates with sustained C-peptide production.

Topics: C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Magnetic Resonance Imaging; Phantoms, Imaging; Portal Vein

This article presents a clinically characterization of the mitochondrial DNA mutation (A3243G) associated with maternally inherited diabetes and deafness (MIDD) syndrome in two families.. Six patients with MIDD and one mutation-positive relative with normal glucose tolerance (NGT) were examined. Fasting serum C-peptide was measured in all subjects and compared with controls having NGT (n = 14). C-peptide response to an intravenous glucose tolerance test (IVGTT) was investigated in the diabetic patients not treated with insulin (n = 3) and in the mutation-positive healthy individual and compared with the controls.. The A3243G heteroplasmy value varied between 5 and 30%. All A3243G carriers had HLA-DR1-DQ5 haplotype, and either the -DQ5 or the -DQ6 allele. The fasting and the serum C-peptide levels at 120 min during the IVGTT did not differ between the A3243G carriers and the controls. A missing first phase and a decreased total C-peptide response was detected in the mutation-positive diabetics compared with controls (p < 0.0001). The same abnormality was found in the A3243G carrier with NGT. Circulating islet cell antibody (ICA) was present in three patients with MIDD. Glutamic acid decarboxylase (GAD), tyrosine phosphatase-like protein IA-2 (IA-2) and mitochondrial antibodies were missing. The diagnosis of MIDD was delayed in each case.. A missing first phase and a decreased total C-peptide response during an IVGTT was characteristic for the A3243G mutation. The fasting C-peptide level of the carriers did not differ from the controls. Circulating ICA was present in some patients, but GAD, IA-2 and mitochondrial antibodies were absent. All subjects had HLA-DR1-DQ5 haplotype, and either -DQ5 or -DQ6 alleles.

Topics: Adult; C-Peptide; Deafness; Diabetes Complications; Diabetes Mellitus; DNA Primers; DNA, Mitochondrial; Family; Female; Glucose Tolerance Test; HLA-DQ Antigens; HLA-DR Antigens; Humans; Male; Middle Aged; Mothers; Pedigree; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus.. The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation.. FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%).. Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Middle Aged; Pancreas, Exocrine; Pancreatic Elastase; Pancreatic Function Tests; Young Adult

Quantitative assessment of pancreatic insulin secretion rate in individuals may help advance our understanding and treatment of diabetes. We describe for the first time the application of a long-established numerical deconvolution procedure in which a prescribed input function is used to represent first-phase pancreatic secretion response to an intravenous glucose challenge (intravenous glucose tolerance test [IVGTT]) in individual subjects. We identify that C-peptide secretory response to an IVGTT can be described by a basal secretion rate (S(b)) (picomoles per liter per minute) and a first-phase secretory response characterized by a Gaussian function. The Gaussian function contains 3 parameters: P(1) (picomoles per liter per minute), which represents the peak rate secretion; P(2) (per square minute), which is related to the inverse of peak width at half-peak height; and P(3) (minutes), which is the time of the peak secretion rate. When applied to data from 8 healthy Chinese subjects, the estimated parameter values (mean +/- SD) were 19.2 +/- 12.9 pmol L(-1) min(-1), 1548 +/- 1143 pmol L(-1) min(-1), 1.09 +/- 1.21 min(-2), and 2.94 +/- 1.13 minutes for S(b), P(1), P(2), and P(3), respectively. The Gaussian input functions are shown to have similar shapes and to be highly concordant in magnitude with secretory responses estimated by means of the method of Eaton et al (1980) and by the ISEC computer program. In conclusion, we have presented a simple, integrated, validated, and easily implemented method suitable for quantifying pancreatic C-peptide and insulin secretion in individual human subjects. The superiority of our method in comparison with other methods is that it uses as an input function the Gaussian, which has been experimentally verified as describing in vivo the profile of pulsatile insulin secretion. The particular strength of our method is that the Gaussian parameters and simple indices derived from them provide a standardized and interpretable means for carrying out comparative investigations aimed at quantifying how pancreatic secretory responses to an IVGTT differ in various demographic groups or in response to therapeutic treatments.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Kinetics; Male; Middle Aged; Models, Biological; Numerical Analysis, Computer-Assisted; Young Adult

Measurement of C-peptide under standardized conditions provides a sensitive and well-established assessment of beta-cell function. We describe the analytical and clinical validation of an automated, microparticle-based chemiluminescent immunoassay method. The assay is designed to measure C-peptide in human serum, plasma and urine.. Assay performance characteristics such as precision and recovery were measured according to protocols established by the Clinical Laboratory Standards Institute (CLSI). A reference range study was conducted. Analytical sensitivity and specificity, interfering substances, recovery, and linearity studies were performed. Method comparison, against the ADVIA Centaur C-Peptide assay (Siemens), was evaluated with clinical specimens from patients with abnormal insulin secretion.. The detection limit for this assay was 0.01 ng/mL. Functional sensitivity (inter-assay imprecision < or = 20%) was 0.015 ng/mL at a coefficient of variation (%CV) of 11.2%. Total imprecision was below 6.5% CV. The assay was linear upon dilution. Comparison with the ADVIA Centaur C-Peptide assay yielded a correlation coefficient (r) of 0.99.. The ARCHITECT C-Peptide assay measures C-peptide rapidly, accurately, and precisely in human serum, plasma and urine. It provides useful improvements for beta-cell function testing and for evaluating the clinical status of a patient in combination with other diabetes markers.

Topics: C-Peptide; Diabetes Mellitus; Glucose Metabolism Disorders; Humans; Immunoassay; Luminescent Measurements; Reagent Kits, Diagnostic; Sensitivity and Specificity

beta-Cell mass declines progressively during the course of diabetes, and various antidiabetic treatment regimens have been suggested to modulate beta-cell mass. However, imaging methods allowing the monitoring of changes in beta-cell mass in vivo have not yet become available. We address whether pancreatic beta-cell area can be assessed by functional test of insulin secretion in humans.. A total of 33 patients with chronic pancreatitis (n = 17), benign pancreatic adenomas (n = 13), and tumors of the ampulla of Vater (n = 3) at various stages of glucose tolerance were examined with an oral glucose load before undergoing pancreatic surgery. Indexes of insulin secretion were calculated and compared with the fractional beta-cell area of the pancreas.. beta-Cell area was related to fasting glucose concentrations in an inverse linear fashion (r = -0.53, P = 0.0014) and to 120-min postchallenge glycemia in an inverse exponential fashion (r = -0.89). beta-Cell area was best predicted by a C-peptide-to-glucose ratio determined 15 min after the glucose drink (r = 0.72, P < 0.0001). However, a fasting C-peptide-to-glucose ratio already yielded a reasonably close correlation (r = 0.63, P < 0.0001). Homeostasis model assessment (HOMA) beta-cell function was unrelated to beta-cell area.. Glucose control is closely related to pancreatic beta-cell area in humans. A C-peptide-to-glucose ratio after oral glucose ingestion appears to better predict beta-cell area than fasting measures, such as the HOMA index.

Topics: Adenoma; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Hair Cells, Ampulla; Humans; Insulin; Insulin-Secreting Cells; Male; Pancreatic Neoplasms; Pancreatitis, Chronic

Topics: C-Peptide; Diabetes Mellitus; Female; Humans; Insulin-Secreting Cells; Pancreas; Pregnancy

To determine the extent of beta-cell function in youth with diabetes and GAD65 and/or IA2 autoantibodies.. Fasting C-peptide levels from 2,789 GAD65- and/or IA2 autoantibody-positive youth aged 1-23 years from the SEARCH for Diabetes in Youth study were used. Preserved beta-cell function was defined on the basis of cut points derived from the Diabetes Control and Complications Trial (DCCT) (fasting C-peptide > or =0.23 ng/ml) and from the U.S. adolescent population of the National Health and Nutrition Examination Survey (NHANES) 5th percentile for fasting C-peptide (> or =1.0 ng/ml). We compared the clinical characteristics between those with and without preserved beta-cell function.. Within the first year of diagnosis, 82.9% of youth had a fasting C-peptide > or =0.23 ng/ml and 31.2% had values > or =1.0 ng/ml. Among those with > or =5 years of diabetes duration, 10.7% had preserved beta-cell function based on the DCCT cutoff and 1.0% were above the 5th percentile of the NHANES population.. Within the 1st year of diagnosis, four of five youth with autoantibody-positive diabetes have clinically significant amounts of residual beta-cell function and about one-third have fasting C-peptide levels above the 5th percentile of a healthy adolescent population. Even 5 years after diagnosis, 1 of 10 has fasting C-peptide above a clinically significant threshold. These findings have implications for clinical classification of youth with diabetes as well as clinical trials aimed to preserve beta-cell function after diabetes onset.

Topics: Adolescent; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Humans; Infant; Insulin-Secreting Cells; Male; Young Adult

Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with homozygous or compound heterozygous mutations. We describe a novel translocation [t(7,19)(p15.2;p13.2)] cosegregating with insulin resistance and pre- and postnatal growth deficiency. Chromosome translocations present a unique opportunity to identify modifying loci; therefore, our objective was to determine the mutational mechanism resulting in this complex phenotype.. Breakpoint mapping was performed by fluorescence in situ hybridization (FISH) on patient chromosomes. Sequencing and gene expression studies of disrupted and adjacent genes were performed on patient-derived tissues. RESULTS Affected individuals had increased insulin, C-peptide, insulin-to-C-peptide ratio, and adiponectin levels consistent with an insulin receptoropathy. FISH mapping established that the translocation breakpoints disrupt INSR on chromosome 19p15.2 and CHN2 on chromosome 7p13.2. Sequencing demonstrated INSR haploinsufficiency accounting for elevated insulin levels and dysglycemia. CHN2 encoding beta-2 chimerin was shown to be expressed in insulin-sensitive tissues, and its disruption was shown to result in decreased gene expression in patient-derived adipose tissue.. We present a likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo.

Topics: Adult; Age of Onset; Antigens, CD; Biomarkers; Blood Glucose; C-Peptide; Chromosome Mapping; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 7; Diabetes Mellitus; DNA-Binding Proteins; Female; Fetal Growth Retardation; Gene Expression Regulation; Growth Disorders; Haplotypes; Humans; In Situ Hybridization, Fluorescence; Insulin; Insulin Resistance; Male; Pregnancy; Receptor, Insulin; Receptors, Steroid; Receptors, Thyroid Hormone; Sequence Analysis, DNA; Signal Transduction; Translocation, Genetic

Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K(+) channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause.. We report a sporadic case of diabetes without ketoacidosis diagnosed on the fourth day of life.. Analysis of the KCNJ11 gene found a novel R365H mutation in the proband and her unaffected father. The functional analysis did not support pathogenicity of this variant. When the patient's diabetes remitted in the seventh month of life, the 6q24 region was analyzed and a paternally inherited duplication was identified.. Our case reports a coincidental novel KCNJ11 variant in a patient with transient neonatal diabetes due to a 6q24 duplication, illustrating the difficulty in testing neonates before the clinical course of neonatal diabetes is known.

Topics: Birth Weight; C-Peptide; Chromosomes, Human, Pair 6; Diabetes Mellitus; Female; Gene Duplication; Genetic Variation; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Male; Mutation, Missense; Potassium Channels, Inwardly Rectifying

Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control dogs) were given 0.5 or 1.0 mg glucagon intravenously. Blood samples were taken before the injection and 10 and 20 minutes after it. Samples were analysed to determine C-peptide, insulin and glucose concentrations, and one sample from each dog was analysed for fructosamine. The median (interquartile range) concentrations of C-peptide in the samples taken at 10 minutes were 0.5 (0.3 to 0.8) nmol/l in the control dogs, 0.1 (0 to 0.2) nmol/l in the diabetic dogs, and 0.3 (0.2 to 0.4) nmol/l in the dogs that had recovered from diabetes. Seven of the 51 dogs showed mild adverse reactions after the injection of glucagon.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Dog Diseases; Dogs; Female; Fructosamine; Glucagon; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Treatment Outcome

Alterations in plasma insulin and C-peptide concentrations following hemodialysis were evaluated using five types of dialyzer, which made of polysulphone, polyethersulfone, cellulose triacetate, polymethylmethacrylate, and polyester-polymer alloy, in diabetic patients. Plasma insulin and C-peptide were cleared by hemodialysis; their clearance rates and reduction rates differed across dialyzer types.

Topics: Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Male; Middle Aged; Renal Dialysis; Reproducibility of Results

The purpose of this study was to examine the relationship of glycemic control and exogenous and endogenous insulin levels with all-cause and cause-specific mortality (ischemic heart disease and stroke) in an older-onset diabetic population.. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an ongoing, prospective, population-based cohort study of individuals with diabetes first examined in 1980-1982. A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older was labeled "older-onset" (n = 1,370). Those participating in the 1984-1986 examination phase (n = 1,007) were included in the analysis. Endogenous insulin was determined by measurements of plasma C-peptide (in nanomoles per liter), and exogenous insulin was calculated in units per kilogram per day. Glycemic control was determined by levels of glycosylated hemoglobin (HbA(1)).. After 16 years of follow-up, 824 individuals died (all-cause mortality); 358 deaths involved ischemic heart disease and 137 involved stroke. C-peptide and HbA(1) were significantly associated with all-cause and ischemic heart disease mortality in our study. The hazard ratio (95% CI) values for all-cause mortality were 1.12 (1.07-1.17) per 1% increase in HbA(1), 1.20 (0.85-1.69) per 1 unit x kg(-1) x day(-1) increase in exogenous insulin, and 1.15 (1.04-1.29) per 1 nmol/l increase in C-peptide and for ischemic heart disease mortality were 1.14 (1.06-1.22), 1.50 (0.92-2.46), and 1.19 (1.02-1.39) for HbA(1), exogenous insulin, and C-peptide, respectively, after adjusting for relevant confounders. C-peptide was associated with stroke mortality only among men (1.65 [1.07-2.53]).. Our results show that individuals with higher endogenous insulin levels are at higher risk of all-cause, ischemic heart disease, and stroke mortality.

Topics: Adult; Age of Onset; Aged; C-Peptide; Cohort Studies; Diabetes Mellitus; Diabetic Retinopathy; Female; Humans; Hypoglycemic Agents; Insulin; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Prospective Studies; Survival Rate; Wisconsin

Both type 2 diabetes and hyperinsulinemia have been related to diminished cognition. To address independent effects of increasing mid-life insulin secretion on late-life cognition, we prospectively examined the relation of plasma C-peptide levels to cognitive decline in a large sample of older women without diabetes or stroke.. Plasma C-peptide levels were measured in 1187 "young-old" women (mean age=64 years) without diabetes in the Nurses' Health Study. Cognitive decline was assessed approximately 10 years later. Three repeated cognitive batteries were administered over an average of 4.4 years using telephone-based tests of general cognition, verbal memory, category fluency, and attention. Primary outcomes were general cognition (measured by the Telephone interview for Cognitive Status [TICS], as well as a global score averaging all tests) and a verbal memory score averaging four tests of word-list and paragraph recall. Linear mixed effects models were used to compute associations between C-peptide levels and rates of cognitive decline.. Higher C-peptide levels were associated with faster decline in global cognition and verbal memory. Compared to those in the lowest C-peptide quartile, multivariable-adjusted mean differences (95% CI) in rates of decline for women in the highest quartile were -0.03 (-0.06,-0.00) units/year for the global score, and -0.05 (-0.09,-0.02) units/year for verbal memory. Each one standard-deviation increase in C-peptide was associated with significantly faster decline on the TICS (p-trend=0.05), global score (p-trend=0.04) and verbal memory (p-trend=0.006).. Higher levels of insulin secretion in those without diabetes may be related to decline in general cognition and verbal memory.

Topics: Adult; Aging; C-Peptide; Cognition; Cognition Disorders; Cohort Studies; Diabetes Mellitus; Female; Humans; Linear Models; Middle Aged; Prospective Studies; Reference Values; Residence Characteristics; United States

Variation within six novel genetic loci has been reported to confer risk of type 2 diabetes and may be associated with beta cell dysfunction. We investigated whether these polymorphisms are also associated with impaired proinsulin to insulin conversion.. We genotyped 1,065 German participants for single nucleotide polymorphisms rs7903146 in TCF7L2, rs7754840 in CDKAL1, rs7923837 and rs1111875 in HHEX, rs13266634 in SLC30A8, rs10811661 in CDKN2A/B and rs4402960 in IGF2BP2. All participants underwent an OGTT. Insulin, proinsulin and C-peptide concentrations were measured at 0, 30, 60, 90 and 120 min during the OGTT. Insulin secretion was estimated from C-peptide or insulin levels during the OGTT using validated indices. We used the ratio proinsulin/insulin during the OGTT as indicator of proinsulin conversion.. In our cohort, we confirmed the significant association of variants in TCF7L2, CDKAL1 and HHEX with reduced insulin secretion during the OGTT (p<0.05 for all). Variation in SLC30A8, CDKN2A/B and IGF2BP2 was not associated with insulin secretion. The risk alleles of the variants in TCF7L2, CDKAL1 and SLC30A8 reduced proinsulin to insulin conversion (p<0.05 for all), whereas the risk alleles in HHEX, CDKN2A/B and IGF2BP2 were not associated with reduced proinsulin to insulin conversion (p>0.6).. Diabetes-associated variants in TCF7L2 and CDKAL1 impair insulin secretion and conversion of proinsulin to insulin. However, both aspects of beta cell function are not necessarily linked, as impaired insulin secretion is specifically present in variants of HHEX and impaired proinsulin conversion is specifically present in a variant of SLC30A8.

Topics: Adult; Area Under Curve; C-Peptide; Cation Transport Proteins; Cyclin-Dependent Kinase 5; Diabetes Mellitus; Female; Germany; Homeodomain Proteins; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Polymorphism, Single Nucleotide; Proinsulin; TCF Transcription Factors; Transcription Factor 7-Like 2 Protein; Transcription Factors; tRNA Methyltransferases; Zinc Transporter 8

Previous studies suggest men with diabetes may be at reduced risk for prostate cancer as compared to men without diabetes. To investigate potential biological mechanisms, hormonal profiles of diabetic men and non-diabetic controls were compared.. In the Health Professionals Follow-Up Study, plasma levels of C-peptide, testosterone, sex-hormone binding globulin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were determined in 171 diabetic men and 3,001 non-diabetic controls. Multiple linear regression analysis was conducted and least square means were calculated for hormones of interest.. Plasma levels of several hormones either < or =1, 1.1-6, 6.1-14.9, or > or =15 years after diagnosis with diabetes were examined. As time since diabetes diagnosis increased, plasma levels of C-peptide and IGFBP-3 significantly decreased (p for trend: C-peptide =.05, IGFBP-3 =.03). While testosterone and SHBG levels both significantly increased with increasing time since diabetes diagnosis (p for trend: testosterone =.02, SHBG =.002), the ratio of testosterone to SHBG decreased, suggesting a reduction in bioavailable testosterone. Plasma IGF-1 levels were lower in diabetics than non-diabetics, but no significant time trend was noted.. This study of hormonal profiles of diabetic versus non-diabetic men identified changes in diabetic men that may be consistent with reduced prostate cancer risk.

Topics: Adult; Aged; C-Peptide; Case-Control Studies; Diabetes Mellitus; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Linear Models; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk; Sex Hormone-Binding Globulin; Surveys and Questionnaires; Testosterone; Time Factors

Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (> or = 126) status.. High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide.. Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes.. Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.

Topics: Arginine; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; Coronary Disease; Cortisone; Diabetes Mellitus; Female; Humans; Hydrocortisone; Hyperinsulinism; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nitric Oxide Synthase; Predictive Value of Tests; Risk Assessment

To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response.. Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response.. Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. The first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones.. We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. In addition, our data suggest that this could be a functional defect.

Topics: Adult; C-Peptide; Coenzymes; Diabetes Mellitus; DNA, Mitochondrial; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Pedigree; Point Mutation; RNA, Transfer, Leu; Ubiquinone; Vitamins

To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers).. Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis.. Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later.. We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

Topics: Adult; Analysis of Variance; Autoantibodies; Autoimmune Diseases; Biomarkers; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Follow-Up Studies; Glutamate Decarboxylase; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Statistics, Nonparametric

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Headache; Humans; Male; Middle Aged; Migraine Disorders; Norway; Odds Ratio; Surveys and Questionnaires

The incretin effect is reduced and the insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is abolished in patients with type 2 diabetes mellitus (T2DM).. To evaluate the causality of this deficiency we investigated 8 patients with chronic pancreatitis (CP) and normal glucose tolerance (NGT) (fasting plasma glucose (FPG): 5.5 (4.5-6.0) mM (mean (range); HbA(1c): 5.8 (5.4-6.3) %) and 8 patients with CP and secondary diabetes not requiring insulin (FPG: 7.1 (6.0-8.8) mM; HbA(1c): 7.0 (5.8-10.0) %) during three 15-mM hyperglycaemic clamps with continuous iv infusion of saline, glucagon-like peptide-1 (GLP-1) or GIP.. The initial (0-20 min) insulin and C-peptide responses were enhanced significantly in both groups by GLP-1 and GIP, respectively, compared to saline (P<0.05). In both groups GLP-1 infusion resulted in significantly greater insulin and C-peptide responses from 20-120 min compared with saline infusion. During GIP infusion the late-phase insulin response (20-120 min) was 3.1+/-1.0 fold greater than during saline infusion in the group of patients with CP and NGT (P<0.05), whereas there was no significant differences in patients with CP and DM.. The lack of GIP amplification of the late insulin response to iv glucose develops alongside the deterioration of glucose tolerance in patients with CP, suggesting that the same may be true for the loss of the GIP effect in patients with T2DM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Male; Middle Aged; Pancreatitis, Chronic

Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.

Topics: Base Sequence; C-Peptide; Diabetes Mellitus; DNA Mutational Analysis; Female; Glyburide; Glycated Hemoglobin; Heterozygote; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Korea; Mutation; Potassium Channels, Inwardly Rectifying; Sulfonylurea Compounds; Treatment Outcome

In this work, we studied the association of the E23K polymorphism of the Kir6.2 ATP-sensitive potassium channels in 212 Czech patients with diabetes mellitus who were diagnosed after the age of 35. Patients were classified into T1DM, LADA and T2DM groups based on C-peptide and GADA levels. Carriers of the predisposing Kir6.2 E23K K allele showed no increased risk of either type of diabetes mellitus development. On the other hand, we found a correlation between E23K SNP of the KCNJ11 gene and C-peptide levels, which may be considered a measure of pancreatic beta-cell activity, although this correlation was not statistically significant. In conclusion, we failed to confirm the Kir6.2 E23K as a genetic marker for T1DM, LADA and T2DM in the Central Bohemian population of the Czech Republic.

Topics: Adult; Age of Onset; C-Peptide; Case-Control Studies; Czech Republic; Diabetes Mellitus; Female; Gene Frequency; Genotype; Glutamic Acid; Humans; Lysine; Male; Middle Aged; Polymorphism, Single Nucleotide; Potassium Channels, Inwardly Rectifying

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fasting; Humans; Insulin Resistance

Circulating adiponectin (ADP) level in diabetic patients was mainly studied from a viewpoint of insulin action, with little being known about the regulation by pancreatic beta-cell function. We thus investigated the relationship between the serum ADP concentration and pancreatic beta-cell function in non-obese [body mass index (BMI) <30 kg/m(2)] diabetic patients. Serum ADP was measured in 239 type 2 diabetic patients, 61 type 1 diabetic patients and 159 non-obese and non-diabetic subjects with enzyme-linked immunosorbent assay. Serum ADP was analyzed separately by gender. In both males and females, the ADP level increased in conjugation with beta-cell dysfunction, estimated by fasting serum C-peptide, and showed marked increase in type 1 diabetic patients. Multivariate analysis in type 2 diabetic patients showed that the fasting serum C-peptide was extracted as an independent and significantly negative modulator for serum ADP in addition to BMI. The ADP level was not associated with the daily dose of injected insulin in the multivariate analysis using insulin treated patients with types 1 and 2 diabetes. These results indicate that pancreatic beta-cell function is one of a significant negative modulator for the circulating ADP level in non-obese diabetic patients and support the presence of an adipoinsular axis.

Topics: Adiponectin; Adiposity; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Obesity; Regression Analysis; Sex Characteristics; Statistics as Topic

The most common complication after allogenic islet transplantation is rejection. This study was to evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation.. Tacrolimus (FK506) + mycophenolate mofetil (MMF) and FK506 + MMF + prednisone (Pred) were administered respectively for 2 weeks to inhibit rejection after allogenic islet transplantation in rats, which were compared with the control group. The concentrations of blood glucose, insulin and C-peptide were determined dynamically in recipients and the sites of transplantation were observed morphologically.. As compared with the control group without immunosuppressive agents, FK506 +MMF and FK506 + MMF + Pred could prolong the survival time of grafts significantly. There were many morphologically intact islets in the liver of recipients 2 months after transplantation. Group FK506 + MMF kept normal levels of blood glucose, insulin and C-peptide beyond 60 days after transplantation. In contrast, group FK506 + MMF + Pred secreted less C-peptide (P<0.05) and maintained a higher level of blood glucose concentration (P<0.01) after the operation. There was no significant difference in insulin concentrations between the two groups. The level of blood glucose beyond the first 2 weeks after drug withdrawal in group FK506 + MMF + Pred decreased obviously (P<0.05), and the secretion of insulin and C-peptide increased. These results were compared with those the first 2 weeks after transplantation and the first 2 weeks after drug withdrawal.. Both regimens of FK506 + MMF and FK506 + MMF + Pred could provide effective immunosuppression. Moreover the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side-effects.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Models, Animal; Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Immunosuppression Therapy; Immunosuppressive Agents; Insulin; Islets of Langerhans Transplantation; Male; Mycophenolic Acid; Prodrugs; Rats; Rats, Sprague-Dawley; Rats, Wistar; Tacrolimus; Transplantation, Homologous

Diabetic macro- and microangiopathy are associated with a high risk of vascular complications. The diabetic patient exhibits a pathological coagulation state, with an increased synthesis of coagulation factors and plasminogen activator inhibitor 1 (PAI-1) as well as an enhanced aggregation of platelets. Previous studies have shown that C-peptide can reduce leucocyte-endothelial cell interaction and improve microvascular blood flow in patients with type 1 diabetes. In the present study, we examined in vivo whether C-peptide is able to reduce platelet activation and through that microvascular thrombus formation.. In the microvessels of cremaster muscle preparations taken from normal and diabetic mice, ferric chloride-induced thrombus formation was analysed using intravital fluorescence microscopy.. I.V. administration of C-peptide in high dose (70 nmol/kg), but not in low dose (7 nmol/kg), caused a significant delay in arteriolar and venular thrombus growth in normal and diabetic mice. This effect was repressed by cremaster muscle superfusion with insulin (100 microU/ml) in diabetic animals, but particularly in normal animals. In parallel, immunohistochemistry demonstrated a higher number of PAI-1-expressing vessels in cremaster muscle tissue from control animals and from animals treated with C-peptide and insulin compared with tissue from animals with C-peptide treatment application alone.. We conclude that C-peptide possesses antithrombotic actions in vivo. A causal role of PAI-1 in this scenario needs to be further addressed. However, the reversal of C-peptide action by insulin may invalidate the use of this peptide as a treatment option to improve rheology and microcirculation in diabetic patients.

Topics: Animals; C-Peptide; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Immunohistochemistry; Insulin; Mice; Microcirculation; P-Selectin; Plasminogen Activator Inhibitor 1; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis

We describe for the first time the direct quantitative analysis of human C-peptide from urine by isotope dilution assay. Implementation of 2-D reverse phase-reverse phase chromatography (2-D RP-RP) with SIM detection resulted in high assay sensitivity (LOQ= 5 pg on column), accuracy, and method ruggedness. Our experiments demonstrate the strong resolving capability of our proposed 2-D RP-RP platform which significantly reduces strong matrix effects and their resulting quantitation error over a wide range of urine concentrations. In contrast, single column methods (both SIM and multiple reaction monitoring) were found acceptable only for strongly diluted urine samples.

Topics: C-Peptide; Calibration; Chromatography, High Pressure Liquid; Diabetes Mellitus; Humans; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

Male mice that are pttg-null develop sexually dimorphic diabetes with hypoinsulinemia secondary to reduced postnatal-cell proliferation and an inability to expand islet cell mass with aging. We therefore examined the effects of sex-steroid manipulation on diabetes development in pttg-/- male mice. Surgical gonadectomy was followed by implantation of 90-day slow-release pellets releasing 17beta-estradiol (0.36 mg/pellet), placebo or dihydrotestosterone (DHT; 12.5 mg/pellet). Mean fasting blood sugars at the end of the study were 414 +/- 54 mg/dl for pttg-/- controls and 371 +/- 14 mg/dl for pttg-/- mice gonadectomized and treated with DHT compared with 124 +/- 40 and 85 +/- 12 mg/dl in gonadectomized pttg-/- males treated with placebo or estradiol, respectively (P < 0.01 compared with control pttg-/-). Gonadectomy with and without estradiol treatment did not increase the very low circulating insulin levels in pttg-null males (fasting insulin 0.44 +/- 0.04 ng/ml in pttg-/- controls, 0.47 +/- 0.07 and 0.4 ng/ml in pttg-/- gonadectomized males treated with placebo or estradiol, respectively). Gonadectomy increased serum adiponectin levels (4.9 +/- 008 microg/ml in pttg-/- controls versus 13 +/- 0.08 and 7.5 +/- 0.6 microg/ml in pttg-/- gonadectomized males treated with placebo or estradiol, respectively; P < 0.001 and P < 0.05), accompanied by increased insulin sensitivity. The results show that gonadectomy delayed, and gonadectomy with additional estradiol treatment prevented, diabetes development in pttg-/- males, possibly through increased insulin sensitivity mediated by elevated serum adiponectin levels. Male-selective effects of disrupted beta-cell proliferation in the absence of pttg are restored by sex-steroid effects on peripheral insulin sensitivity.

Topics: Adiponectin; Androgens; Animals; Blood Glucose; C-Peptide; Carrier Proteins; Cell Proliferation; Diabetes Mellitus; Dihydrotestosterone; Estradiol; Gonadal Steroid Hormones; Insulin; Insulin-Secreting Cells; Leptin; Male; Mice; Mice, Knockout; Neoplasm Proteins; Orchiectomy; Securin; Sex Characteristics

The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients.. Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743.. Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003).. Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Diabetes Mellitus; DNA Primers; Female; Genotype; Glutamate Decarboxylase; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Insulin-Secreting Cells; Isoenzymes; Male; Sweden

To determine differences in pancreatic B-cell function in relation to islet antibodies at diagnosis of diabetes and 3 years later in subjects aged 35-64 years old compared with those aged 0-34 years.. From a population-based diabetes register, 46 (0-34 years old) and 323 (35-64 years old) incident diabetic patients were investigated at diagnosis and 3 years later. Islet cell antibodies (ICA, GADA and IA-2A) and fasting plasma C-peptide were measured.. Islet antibodies were found in 80% of the subjects aged 0-34 years and in 11% of those aged 35-64 years at diagnosis. ICA and GADA was the only combination of two islet antibodies detected in those aged 35-64 years and was, with or without IA-2A, associated with significantly lower median fasting C-peptide values than in those without or with only one antibody [0.35 nmol/l, interquartile range (IQR) 0.63 vs. 0.85 nmol/l, IQR 0.49; P = 0.0004]. However, fasting C-peptide in subjects aged 35-64 years old with multiple islet antibodies was higher than in those aged 0-34 years with islet antibodies (median 0 nmol/l, IQR 0.16, P = 0.0019). After 3 years' follow-up, fasting C-peptide was even lower in subjects aged 35-64 years old with three islet antibodies (median 0.14 nmol/l, IQR 0.27; P = 0.05).. Islet antibodies were common in adults at diagnosis of diabetes. The combination of ICA and GADA indicates impaired B-cell function at diagnosis of diabetes in those aged 35-64 years old.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Humans; Infant; Infant, Newborn; Insulin-Secreting Cells; Islets of Langerhans; Middle Aged

To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with beta-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload.. We measured fasting glucose, insulin and C-peptide levels in 24 patients with beta-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated.. Fasting glucose levels in patients were increased compared with control subjects (5.5 +/- 0.12 vs. 4.7 +/- 0.13 mmol/l, mean +/- SEM, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SC(HOMA)) was lower in thalassaemic patients (SC(HOMA) 88.5 +/- 11.11 vs. 184.3 +/- 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SC(HOMA) was higher in the patients with NFG compared with those with IFG patients (110.6 +/- 17.63 vs. 66.3 +/- 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISI(HOMA)) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SC(HOMA) (r = 0.45, P = 0.02) and negatively with ISI(HOMA) (r = -0.43, P = 0.03).. These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in beta-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent.

Topics: Adult; beta-Thalassemia; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Male; Models, Biological

Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels.. The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes.. The study setting was the Physicians' Health Study-U.S. male physicians.. Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years).. The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors.. On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant.. Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes.

Topics: C-Peptide; Cognition; Diabetes Mellitus; Health Status; Humans; Interviews as Topic; Male; Middle Aged; Reproducibility of Results; Telephone

Although people with diabetes have decreased lung function, the dose-response relation between measures of glucose control and lung function in nondiabetic people is not known. The authors used data from the Third National Health and Nutrition Examination Survey (1988-1994) to investigate the relation between glucose tolerance test response and other measures of glucose homeostasis and lung function in an adult population without a clinical diagnosis of diabetes. Plasma glucose level 2 hours after oral administration of 75 g of glucose was inversely related to forced expiratory volume in 1 second (FEV(1)), with a difference of -144.7 ml (95% confidence interval: -231.9, -57.4) for persons in the highest quintile of postchallenge glucose compared with the lowest. Similar inverse associations with FEV(1) were found for other measures of glucose autoregulation. Lung function did not appear to be related to fasting glucose level. Similar associations were seen for forced vital capacity (FVC) but not for the FEV(1):FVC ratio. In the total study population, persons with previously diagnosed diabetes had an FEV(1) 119.1 ml (95% confidence interval: -161.5, -76.6) lower than persons without diabetes. This effect was greater in those with poorly controlled diabetes. These findings suggest that impaired glucose autoregulation is associated with impaired lung function.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Forced Expiratory Volume; Glucose; Health Status; Humans; Insulin; Lung; Male; Middle Aged; Nutrition Surveys; Respiratory Function Tests; United States

Topics: Abnormalities, Multiple; Adult; Anemia, Aplastic; C-Peptide; Diabetes Complications; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Humans; Infant; Neutropenia; Syndrome

Growing evidence suggests that type 2 diabetes mellitus and hyperinsulinemia may be related to diminished cognition. To help differentiate between the effects of diabetes and insulin, we examined the relation of insulin to cognitive function among nondiabetic participants of the Nurses' Health Study.. We measured the C peptide level, representing insulin secretion, in blood samples provided by 718 women from June 14, 1989, to October 4, 1990, when they were aged 61 to 69 years. We administered telephone interviews an average of 10 years after blood collection, testing general cognition, verbal memory, category fluency, and attention; second cognitive assessments were conducted 2 years later. The primary outcomes were global cognitive function across all tests and verbal memory. We used regression models to estimate multivariable-adjusted mean differences in cognitive function and cognitive decline, and odds of cognitive impairment, across C peptide levels.. Cognitive function was worse among women in the fourth C peptide quartile compared with those in the first quartile (eg, on the global score combining all cognitive tests, the multivariable-adjusted mean difference was -1.7 standard units [95% confidence interval, -2.9 to -0.6 standard units]; P = .002); the odds of cognitive impairment (defined as the worst 10% of the distribution) were 3-fold higher among women in the fourth vs first quartile (95% confidence interval, 1.3-7.8). On verbal memory, women in the fourth quartile scored significantly worse than those in the first quartile; the odds of impairment were 2.8-fold higher (95% confidence interval, 1.1-7.0). Consistent findings were observed for cognitive decline.. Higher insulin secretion may be related to worse cognition, even among those without diabetes.

Topics: Aged; C-Peptide; Cognition; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Insulin; Insulin Secretion; Middle Aged; Odds Ratio; Regression Analysis; Reproducibility of Results; Surveys and Questionnaires; Time Factors

We evaluate the prognostic significance of chronic liver diseases followed by diabetes mellitus in 40 patients by Child class, immunoreactive insulinemia (IRI), C peptide (CP) and pancreolaury-test (PLT) at 5 years. Death and hepatic insufficiency prevalence were significantly higher in cirrhotic diabetics, and in those diabetics with a lower insulin secretion (IRI, CP). Insulin hyposecretion (lower IRI, CP) was found in cirrhotic with abnormal PLT (below 20%). The onset of diabetes mellitus in liver cirrhosis has a bad prognosis when it is caused by decreased insulin secretion produced by chronic pancreatitis or pancreatic insufficiency.

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Liver Cirrhosis; Longitudinal Studies; Predictive Value of Tests; Prognosis

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is probably involved in the genetic regulation of insulin secretion. The aim of this study was to investigate the association of INS VNTR polymorphism with the presence of glutamic acid decarboxylase antibodies (GADA) and C-peptide levels in patients with the onset of diabetes after 35 years of age. We investigated 117 patients, median of age 63 (range 40-83) years, median of diabetes duration 8 (range 1-30) years; 31 GADA-positive and 86 GADA-negative subjects. INS VNTR polymorphism was typed indirectly using - 23HphI (T/A) polymorphism, which is in complete linkage disequilibrium with INS VNTR. The I/I, I/III and III/III genotypes were found in 22 (71 %), 8 (26 %), 1 (3 %) GADA-positive individuals and in 39 (45 %), 35 (41 %), 12 (14 %) GADA-negative individuals, respectively. The Class I allele and the genotype I/I were significantly associated with the presence of GADA (OR=2.72, CI 95 %=1.29-5.73 and OR=2.95, CI 95 %=1.22-7.13). The presence of Class III allele was significantly associated with a higher level of postprandial C-peptide in GADA-positive subjects, even when regarding the duration of diabetes. Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects.

Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Antibodies; C-Peptide; Confidence Intervals; Diabetes Mellitus; DNA; Female; Gene Frequency; Genotype; Glutamate Decarboxylase; Heterozygote; Homozygote; Humans; Insulin; Male; Middle Aged; Minisatellite Repeats; Odds Ratio; Patient Selection; Polymorphism, Genetic; Postprandial Period

Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects.. We conducted a cross-sectional study on 521 consecutive diabetic subjects newly referred to a Diabetes Clinic in 1996. The subjects were categorized into underweight (< 18.5 kg/m(2)), normal weight (18.5-23 kg/m(2)) and overweight (>/= 23 kg/m(2)) according to the re-defined WHO criterion for obesity in Asia Pacific Region. Metabolic and anthropometric parameters were compared between groups with different levels of obesity.. In this cohort, 5.8, 30.6 and 63.7% of subjects were underweight, normal weight and overweight, respectively, using the 'Asian' criteria. Of these 521 subjects, 20% had fasting C-peptide less than 0.2 nmol/l, suggesting insulin deficiency. Fasting C-peptide showed linear increasing trend (P < 0.001) while HbA(1c) showed decreasing trend (P = 0.001) with BMI after adjustment for duration of disease. There were more subjects in the underweight group who were treated with insulin (41.3% vs. 13.9 and 8.2%, P < 0.001). Although homeostasis model assessment was similar amongst the three groups, systolic (P = 0.006) and diastolic blood pressure (P < 0.001) and triglyceride (P < 0.001) showed increasing, while HDL-C (P < 0.001) showed decreasing, trends across different BMI groups. The underweight patients had the lowest C-peptide and highest HbA(1c) while overweight patients had the highest C-peptide, blood pressure, triglyceride but lowest HbA(1c) levels.. In Chinese Type 2 diabetic patients, lean subjects had predominant insulin deficiency and obese subjects had features of metabolic syndrome. Clinicians should have low threshold to initiate insulin therapy in lean Type 2 diabetic patients with suboptimal glycaemic control. In obese diabetic patients, aggressive control of multiple cardiovascular risks is of particular importance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; C-Peptide; Cholesterol; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hong Kong; Humans; Insulin; Male; Middle Aged; Obesity; Patient Education as Topic

We evaluated new immunochemiluminometric assays (ICMAs) for insulin and C-peptide (ADVIA Centaur Insulin & C-Peptide-Serum assays). Both ADVIA Centaur assays are two-site sandwich immunoassays using direct chemiluminescent technology. Precision was investigated using serum pools at three levels of the two analytes, measured in duplicate for 10 days. Total Coefficient of Variations (CVs) were 5, 7 and 4% for insulin and 9, 6 and 10% for C-peptide, with intra-assay precisions of 5, 4 and 5% and 5, 3 and 3%, respectively. The minimum detectable concentrations were 0.5 mU/L and < 0.1 microg/L for insulin and for C-peptide, respectively. Day-to-day reproducibility of single measurements was 5.4, 7.1 and 4.3% for pools with an insulin concentration of 0.6 mU/L, 2.0 mU/L and 4.0 mU/L; it was 4.4, 6.6 and 5.3% for pools with a C-peptide concentration of 0.2, 0.3 and 1.0 microg/L. The functional sensitivity did not differ from 3 SD Minimal Detectable Concentration (MDC) (0.5 mU/L for insulin and < 0.1 microg/L for C-peptide). The linearity was good in the range of 0.6-20 mU/L for insulin and 0.3-9 microg/L for C-peptide. The comparison with the RIA used in our laboratory was analyzed by Passing-Bablok and Bland-Altman plots and revealed a proportional bias of approximately 20% (slope: 1.20; CI: 1.14 to 1.26) for C-peptide and a systematic bias of -1.6 mU/L (slope: 0.94; CI: 2.7 to -0.5) for insulin which should not have any clinical consequence in the interpretation of results. Finally, we tested the influence of hemolysis on insulin in serum and plasma and found the same negative effect for both samples when more than 2% of red cells were hemolyzed, and this effect increased with the lag time before freezing. In conclusion, both assays were satisfactorily correlated with the routine RIA test used in our laboratory. The major problem was the sensitivity to hemolysis which is common to all insulin immunometric assays.

Topics: Autoanalysis; C-Peptide; Diabetes Mellitus; Hemolysis; Humans; Immunoassay; Insulin; Luminescent Measurements; Reproducibility of Results

The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas.. Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period.. Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels.. Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Topics: Aged; Aged, 80 and over; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Humans; Islets of Langerhans Transplantation; Length of Stay; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Transplantation, Autologous; Treatment Outcome

To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia.. Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore.. The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA.. Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.

Topics: Administration, Oral; Adolescent; Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Child; China; Diabetes Mellitus; Diabetes Mellitus, Type 2; Family Health; Female; Glycated Hemoglobin; Hong Kong; Humans; Hypoglycemic Agents; India; Insulin Resistance; Malaysia; Male; Singapore

In our study, we investigated the relationship of HLA class II alleles to antibody production against glutamic acid decarboxylase (GADab) and to C-peptide secretion (CP) in diabetic patients. A group of 334 patients (190 women) diagnosed after 35 years of age and 99 control subjects were studied. Patients were divided into four groups according to concentrations of CP and GADab, respectively (CP high/low, GADab positive/negative). HLA DQB1 and DRB1 alleles were genotyped by SSP-PCR. The significance of DQB1 and DRB1 risk alleles was evaluated by examination of their odds ratios computed by testing 2x2 tables considering Bonferonis' corrected P<0.05 as significant. We found strong association between the HLA DRB1*03 risk allele and presence of GADab, and close relationship of the HLA DRB1*04 and HLA DQB1*0302 risk alleles with decreased CP level. Taken together we conclude that the DRB1*04 and DQB1*0302 alleles are associated with progressive decrease of CP level, while DRB1*03 is a significant genetic marker of autoantibody (GADab) development.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Antibodies; C-Peptide; Diabetes Mellitus; Female; Genetic Predisposition to Disease; Glutamate Decarboxylase; HLA-DQ Antigens; HLA-DQ beta-Chains; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Male; Middle Aged

Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta-thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors.. To study the prevalence of diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian beta-thalassemic patients and to evaluate the possible role of genotyping in the pathogenesis of diabetes associated with beta-thalassemia.. A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31 (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia major and eight thalassemia intermedia; compared to 15 age- and sex-matched controls. All were subjected to history and examination, laboratory investigations: complete blood count (CBC), serum ferritin, liver function tests, hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in thalassemic patients with abnormal glucose tolerance.. The prevalence of diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major, whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C-peptide was lower in beta-thalassemic patients compared to controls (p <0.001); the level was significantly higher in patients complicated by diabetes or IGT compared with other thalassemic patients (p <0.001). Chronic hepatitis C was detected in all patients (100%) with abnormal glucose tolerance. Genotyping showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose tolerance.. Abnormal glucose tolerance is common in multiply transfused beta-thalassemia major patients, which could be attributed to progressive and early loss of beta-cell mass, along with persistent insulin resistance. Chronic hepatitis C may play a role in the development of abnormal glucose tolerance. An association between diabetes and genotyping IVS II nt 745 was found. Patients with this particular genotype are advised to check their blood glucose every 6 months to detect early occurrence of diabetes.

Topics: Adolescent; Adult; beta-Thalassemia; Blood Transfusion; C-Peptide; Child; Diabetes Mellitus; Egypt; Female; Genotype; Glucose Intolerance; Hepatitis C, Chronic; Humans; Male

To investigate the possibility of using C-peptide to replace insulin in homeostasis model assessment (Homa) to evaluate insulin resistance and islet beta cell function.. Oral glucose tolerance test (OGTT) was performed in 21 normal subjects, whose venous blood was drawn before taking glucose and 30, 60, 120 minutes after taking glucose. Insulin and C-peptide were determined with radioimmune assay. Homa indices of insulin resistance and islet beta cell function were calculated. Multiple stepwise linear regression model of insulin resistance was measured using C-peptide x blood glucose as independent variables and Homa-IR was used as the dependent variable, while the model of islet beta cell function was determined using C-peptide/(fasting blood glucose - 3.5) as the independent variable and Homaislet as the dependent variable.. The modified Homa formula were: Homa-IR (CP) = 1.5 + fasting blood glucose x fasting C-peptide/2800 (F = 5. 511, P = 0.029), Homa-islet (CP-Normal) = 0.27 x fasting C-peptide /(fasting blood glucose - 3.5) + 50, and Homa-islet (CP-DM) = 0.27 x fasting C-Peptide/(fasting blood glucose - 3.5) (F = 212.961, P = 0.000), respectively. The modified Homa-IR (CP) and Homa-IR, Homa-islet (CP) and Homa-islet were highly correlated (r =0.689 and r = 0.788; all P = 0.000). Using Homa and modified Homa formula to evaluate the insulin resistance and islet beta cell function both in the normal and diabetic subjects was similar.. Fasting C-peptide can substitute insulin in Homa model to assess insulin resistance and islet beta cell function. The modified homeostasis model assessment may be applied in the diabetics using exogenous insulin.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Mathematics; Middle Aged

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type 2 diabetes. Twenty-one type 2 diabetes subjects with hypertriglyceridemia (triacylglycerol >2.2 mmol/l) and 10 age-matched nondiabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during minutes 60-120. In one of two tests, the subjects ingested 250 mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in 17 of the diabetic subjects after 3 days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in nondiabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in nondiabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects, Acipimox increased integrated insulin secretion rates during minutes 60-120 in the 50% having the lowest levels of hemoglobin A(1c) (379 +/- 34 vs. 326 +/- 30 pmol x kg(-1) x min(-1) without Acipimox, P < 0.05). A 3-day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type 2 diabetic subjects.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Dietary Proteins; Energy Intake; Exercise; Fasting; Fatty Acids; Female; Glucagon; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertriglyceridemia; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Proinsulin; Pyrazines

We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years.. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide.. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up.. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Humans; Incidence; Islets of Langerhans; Societies, Medical; Sweden; United States; World Health Organization

The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence and clinical characteristics of PTDM in Korean renal allograft recipients undergoing tacrolimus-based immunosuppression were examined.. A total of 21 patients taking tacrolimus as primary immunosuppressant were recruited and tested with a serial 75-g oral glucose tolerance test at 0, 1, 3, and 6 months after renal transplantation.. The cumulative incidence of PTDM was 52.4% at 1 month and 57.1% at 3 and 6 months. The baseline characteristics of the PTDM group were old age (especially >40 years), a high BMI, a high fasting glucose level, a high plasma insulin level, and increased insulin resistance. Among these parameters, old age was the only independent risk factor. The insulin secretory capacity in the PTDM group was maximally suppressed 3 months after transplantation. Thereafter, it was gradually restored along with dose reduction of tacrolimus.. Routine screening for PTDM is necessary in patients over 40 years of age who are undergoing a relatively higher dose tacrolimus therapy during the early course of postrenal transplantation.

Topics: Adult; C-Peptide; Cholesterol; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Incidence; Insulin; Kidney Transplantation; Male; Postoperative Complications; Societies, Medical; Tacrolimus; Time Factors; Triglycerides; United States

To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes.. The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged > or =25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants.. Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA(1c), and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis.. This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.

Topics: Age of Onset; Aged; Albuminuria; Australia; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Prevalence; Risk Factors; Smoking

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted in response to meal ingestion, thereby enhancing postprandial insulin secretion. Therefore, an attenuated incretin response could contribute to the impaired insulin responses in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. Plasma concentrations of incretin hormones (total, reflecting secretion and intact, reflecting potential action) were measured during two meal tests (260 kcal and 520 kcal) in eight type 1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic patients, and eight obese healthy subjects. Both in diabetic patients and in healthy subjects, significant increases in GLP-1 and GIP concentrations were seen after ingestion of both meals. The incretin responses were significantly higher in all groups after the large meal, compared with the small meal, with correspondingly higher C-peptide responses. Both type 1 and type 2 diabetic patients had normal GIP responses, compared with healthy subjects, whereas decreased GLP-1 responses were seen in type 2 diabetic patients, compared with matched obese healthy subjects. Incremental GLP-1 responses were normal in type 1 diabetic patients. Increased fasting concentrations of GIP and an early enhanced postprandial GIP response were seen in obese, compared with lean healthy subjects, whereas GLP-1 responses were the same in the two groups. beta-cell sensitivity to glucose, evaluated as the slope of insulin secretion rates vs. plasma glucose concentration, tended to increase in both type 2 diabetic patients (29%, P = 0.19) and obese healthy subjects (22% P = 0.04) during the large meal, compared with the small meal, perhaps reflecting the increased incretin response. We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is normal in type 1 diabetic patients; and 2) that it is possible to modulate the beta-cell sensitivity to glucose in obese healthy subjects, and possibly also in type 2 diabetic patients, by giving them a large meal, compared with a small meal.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Feeding Behavior; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity; Peptide Fragments; Protein Precursors; Random Allocation

Insulin resistance is nearly universal in patients with nonalcoholic steatohepatitis (NASH) when tested by glucose tolerance tests or clamp methods. However, the pattern of insulin resistance in these patients after a physiological challenge is unknown. We conducted a study to characterize the metabolic response to a mixed meal in nondiabetic patients with NASH (NDN) and to identify anthropometric determinants of insulin resistance in these patients.. Serum insulin, C-peptide, glucose, and free fatty acid (FFA) levels were measured at 0, 30, 60, 90, and 120 min after a 500-kcal standard meal in 18 NDN and 18 age-, gender-, and body mass index (BMI)-matched controls. Correlations were made between insulin resistance and various anthropometric, calorimetric, and serological variables.. Compared with controls, NDN had significantly higher levels of insulin and C-peptide at baseline and after the mixed meal. However, glucose levels were not different either at baseline or after the meal. NDN had higher fasting levels of FFA than the controls (459 +/- 190 vs 339 +/- 144 micro mol/L, respectively, p = 0.03); however, meal-induced suppression in lipolysis was similar between the two groups (39 +/- 113% vs 46 +/- 60%, p = 0.8). Insulin resistance was significantly correlated with BMI (r = 0.39, p = 0.02) and visceral fat (r = 0.50, p = 0.004). Whereas BMI, percent total body fat, and subcutaneous abdominal fat were similar between the groups, the NASH group had significantly higher percent visceral fat compared with controls (28 +/- 10% vs 22 +/- 14%, p = 0.02).. NDN are significantly hyperinsulinemic, both at fasting and after the mixed meal; however, their glucose homeostasis and suppression in lipolysis after a meal challenge are maintained. Insulin resistance in these patients is likely related to their higher visceral fat mass.

Topics: Adult; Anthropometry; C-Peptide; Chronic Disease; Diabetes Mellitus; Dietary Fats; Fatty Liver; Female; Glucose; Humans; Hyperinsulinism; Insulin Resistance; Lipid Metabolism; Lipolysis; Male; Middle Aged

Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection. We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces. In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

Topics: Aged; Aged, 80 and over; Biopsy; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Glycosylation; Hemoglobins; Humans; Insulinoma; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Time Factors; Transplantation, Autologous

The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state.. This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration.. During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels.. The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Graft Survival; Humans; Hypoglycemic Agents; Insulin; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Sulfonylurea Compounds; Survival Analysis; Time Factors

The transcription factor FOXC2 plays a key role in adipocyte differentiation and the FOXC2 gene is a candidate gene for Type 2 diabetes, obesity and dyslipidaemia. We investigated whether the FOXC2 -512C>T promoter variant is associated with Type 2 diabetes or its intermediary phenotypes in glucose tolerant subjects.. The variant was genotyped using PCR-RFLP in 705 unrelated Type 2 diabetic patients, 505 unrelated glucose-tolerant control subjects and 219 glucose-tolerant offspring of Type 2 diabetic probands.. The frequency of the T-allele was 58% (95% CI 56-61%) and 59% (56-62%) among the Type 2 diabetic patients and the unrelated glucose-tolerant control subjects, respectively ( p=0.6). Among the glucose-tolerant subjects, the T-allele carriers had higher fasting serum triglyceride ( p=0.03), fasting serum C-peptide concentrations ( p=0.009) and insulinogenic index ( p=0.04). Furthermore, in glucose-tolerant women, the waist-to-hip ratio was significantly higher in carriers of the T-allele.. Our data suggest that the FOXC2 -512C>T variant is not associated with Type 2 diabetes. However, among glucose-tolerant subjects the variant is associated with hypertriglyceridaemia and increased fasting serum C-peptide.

Topics: Base Sequence; Body Constitution; C-Peptide; Denmark; Diabetes Mellitus; DNA Primers; DNA-Binding Proteins; Female; Forkhead Transcription Factors; Genetic Variation; Glucose Tolerance Test; Humans; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Reference Values; Sequence Deletion; Transcription Factors; White People

Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose-dependent insulinotropic polypeptide (GIP) is less effective. Our investigation evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C-peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes.. Protocol 1: eight Type II diabetic patients and eight matched healthy subjects received i.v. bolus injections of GLP-1(2.5 nmol) or GIP(7.5 nmol) concomitant with an increase of plasma glucose to 15 mmol/l. Protocol 2: eight Type II diabetic patients underwent a hyperglycaemic clamp (15 mmol/l) with infusion (per kg body weight/min) of either: 1 pmol GLP-1 (7-36) amide (n=8), 4 pmol GIP (n=8), 16 pmol GIP (n=4) or no incretin hormone (n=5). For comparison, six matched healthy subjects were examined.. Protocol 1: Type II diabetic patients were characterised by a decreased "early phase" response to both stimuli, but their relative response to GIP versus GLP-1 stimulation was exactly the same as in healthy subjects [insulin (C-peptide): patients 59+/-9% (74+/-6%) and healthy subjects 62+/-5% (71+/-9%)]. Protocol 2, "Early phase" (0-20 min) insulin response to glucose was delayed and reduced in the patients, but enhanced slightly and similarly by GIP and GLP-1. GLP-1 augmented the "late phase" (20-120 min) insulin secretion to levels similar to those observed in healthy subjects. In contrast, the "late phase" responses to both doses of GIP were not different from those obtained with glucose alone. Accordingly, glucose infusion rates required to maintain the hyperglycaemic clamp in the "late phase" period (20-120 min) were similar with glucose alone and glucose plus GIP, whereas a doubling of the infusion rate was required during GLP-1 stimulation.. Lack of GIP amplification of the late phase insulin response to glucose, which contrasts markedly to the normalising effect of GLP-1, could be a key defect in insulin secretion in Type II diabetic patients.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Synergism; Female; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Hypoglycemic Agents; Injections, Intravenous; Insulin; Male; Middle Aged; Obesity; Peptide Fragments; Protein Precursors; Reference Values; Time Factors

Polymorphisms in beta-cell transcription factor genes, Ala45Thr in the NeuroD1 gene and Arg121Trp in the Pax4 gene, have been reported. To clarify the role of these mutations in the pathogenesis of late-onset diabetes, we examined the insulin secretion and sensitivity in diabetic patients carrying the homozygous mutation in the NeuroD1 gene or Pax4 gene. We screened for the polymorphisms in NeuroD1 and Pax4 genes in 296 late-onset diabetic patients and 177 unrelated control subjects over 60 years of age. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by direct sequencing. Acute insulin secretion was evaluated using a 2-compartment model analysis of C-peptide kinetics after intravenous glucose load (CS1). Insulin sensitivity was estimated by the insulin-modified minimal model analysis (Si). Four diabetic patients carried the homozygous mutation (Thr/Thr) in the NeuroD1 gene and 3 patients carried the homozygous mutation (Trp/Trp) in the Pax4 gene, while both homozygous mutations were not detected in the control subjects. In patients A, B, C, and D with homozygous mutations in NeuroD1, CS1 (normal range, 6.8 to 18.5 ng/mL/min) was 0.508, 1.481, 1.223, and 1.584 ng/mL/min, respectively, and Si (normal range, 2.6 to 7.6 x 10(-4)/min/[microU/mL]) was 0.727, 3.31, 3.79, and 0.00 x 10(-4)/min/(microU/mL), respectively. In patients X, Y, and Z with homozygous mutation in Pax4, CS was 0.418, 0.208, and 1.279 ng/mL/min, respectively, and Si was 1.11, 2.88, and 0.00 x 10(-4)/min/(microU/mL), respectively. Since acute insulin secretion in response to glucose was markedly impaired and insulin resistance was varied in the patients carrying the homozygous mutations in the NeuroD1 and Pax4 genes, the mutations are ones of the factors involved in the beta-cell dysfunction and do not relate to the insulin resistance. These homozygous mutations appear to play a part in the pathogenesis of beta-cell defect in about 2.5% of Japanese patients with late-onset diabetes.

Topics: Aged; Alleles; Amino Acid Sequence; Basic Helix-Loop-Helix Transcription Factors; C-Peptide; Diabetes Mellitus; DNA-Binding Proteins; Gene Frequency; Genotype; Glucose; Homeodomain Proteins; Homozygote; Humans; Injections, Intravenous; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Middle Aged; Mutation; Paired Box Transcription Factors; Trans-Activators; Transcription Factors

Tumor-induced pancreatic damage or insulin resistance may be responsible for diabetes in pancreatic cancer (PC) patients, but the exact cause of association remains controversial. In this study, we aimed to investigate the prevalence of diabetes in patients with PC in central Anatolia, Turkey, and to evaluate whether diabetes is caused by PC. A total of 40 patients with primary PC were enrolled in the study. 13 (32.5%) of the patients had diabetes before PC diagnosis. Oral glucose tolerance test was performed in the remaining 27 patients. The period between the diagnosis of diabetes and detection of PC was less than 1 year in seven (17.5%) patients who had previous diabetes. Recent-onset diabetes and impaired glucose tolerance were detected in 13 (32.5%) and two (5%) of the PC patients, respectively. The prevalence of recent-onset and shortly-before-diagnosed diabetes has been found very high (50%) in our patients with PC. Interestingly, we determined higher levels of insulin and C-peptide in PC patients having abnormal glucose tolerance than patients having normal glucose tolerance. In conclusion, as it has been reported in other population, we determined high prevalence of diabetes in PC patients in central Anatolia. High insulin and C-peptide level indicate that different mechanisms such as insulin resistance may be responsible for abnormal glucose tolerance in PC patients other than the tumor caused insulin deficiency.

Topics: C-Peptide; Comorbidity; Diabetes Complications; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Pancreatic Neoplasms; Prevalence; Time Factors; Turkey; World Health Organization

We aimed to characterize a cohort of 'atypical' diabetic patients of sub-Saharan African origin and to analyse possible determinants of long-term remission.. Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti-GAD, anti-ICA and HLA class II) markers of Type 1 diabetes were compared with a 90-non-diabetic unrelated adult African population.. Twenty-one ketonuric patients (age 42 +/- 9 (sd) years; body mass index (BMI) 26 +/- 3 kg/m2) were initially insulin-treated (IT), and 21 non-ketonuric patients (age 38 +/- 8 years; BMI 26 +/- 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 +/- 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3-64.4) and stimulated C-peptide (OR 8.17, 95% CI 1.5-44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin-treated NIT. Anti-GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P < 0.001) without significant difference between the subgroups.. Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long-term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long-term remission.

Topics: Acute Disease; Adult; Africa South of the Sahara; Autoantibodies; C-Peptide; Diabetes Mellitus; Drug Administration Schedule; Follow-Up Studies; Genetic Predisposition to Disease; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Logistic Models; Middle Aged; Remission Induction; Time Factors

The subject was a 26-year-old Japanese woman of 148 cm height, 96.2 kg of body weight (BW) (body mass index (BMI) of 43.8 kg/m(2)). She was referred to our hospital on May 1, 2000 for the evaluation of marked hyperglycemia with clinical symptom of general malaise, polydipsia, and ketonuria (3+). She did not smoke, or drink alcohol. But, she tended to eat lots of sweet food every day before the onset of this symptom. Her father was diagnosed type 2 diabetes mellitus. Her fasting plasma glucose and HbA(1c), and serum C-peptide were 398 mg/dl, 7.8% and less than 0.05 ng/ml [normal range: 0.94-2.8], respectively. She tested negative for anti-glutamic acid decarboxylase (GAD) antibodies and islet-cell antibodies. C-peptide level in her urine was as low as 3.4 microg/day. We immediately started insulin treatment under the diagnosis of abrupt onset of diabetes mellitus with diabetic ketoacidosis on the day of her admission, and the insulin treatment was continued after her being discharged. She showed continuous BW reduction until her BW reached approximately 60 kg, followed by her BW being plateau. During the period, intra-abdominal visceral fat (VF) and subcutaneous fat (SF) volume assessed by helical computerized tomography (CT) showed a substantial reduction [3.9-0.5 l for VF, 19-3.2 l for SF volume]. Pre-heparin plasma lipoprotein lipase (LPL) mass showed a considerably lower value when she had continuous BW reduction than did it when her BW reduction discontinued. These findings suggest that in this subject, continuous BW reduction after the abrupt onset of diabetes is closely associated with intra-abdominal fat mass reduction, which may be related to decreased production of LPL.

Topics: Adipose Tissue; Adult; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Japan; Leptin; Lipids; Obesity; Regression Analysis; Tomography, X-Ray Computed

Patients with cirrhosis of the liver suffer from hyperinsulinaemia and a certain degree of insulin resistance. More frequently than in the rest of the population they have diabetes. Transjugular intrahepatic portosystemic shunts (TIPS) as a therapeutic method in complications of portal hypertension lead to rapid haemodynamic changes in the liver. The objective of the submitted work was to assess whether TIPS has an impact on insulinaemia and whether it influences insulin resistance in patients with cirrhosis of the liver.. The authors evaluated a group of 22 patients with cirrhosis of the liver (10 diabetics and 12 subjects without diabetes) indicated for TIPS. They investigated the insulin and C-peptide concentration in blood obtained by catheterization from the hepatic and portal vein before and after TIPS and in the peripheral blood before TIPS, 1 hour, 1 day, 1 week and 1 month after TIPS. The insulin resistance was examined by the method of the hyperinsulin euglycaemic clamp (HEC) before TIPS, 1 day, 1 week, and 1 month after TIPS. The levels of C-peptide and insulin were assessed by the IRMA method. The blood sugar level in HEC was measured by means of a Hemocue apparatus. The results were evaluated by the non-parametric Wilcoxon test for two dependent samples.. Both groups (diabetics and non-diabetics) were comparable as to age, sex, etiology of liver cirrhosis and indication for TIPS. After introduction of TIPS a change of insulin clearance occurred (p = 0.01) and a change of the insulin level in the hepatic vein immediately after TIPS (p = 0.02). Insulin clearance before TIPS was 37-90% (median 54%) and after TIPS it declined to 0-79% (median 38%) (p = 0.01). Already 1 hour after the operation the authors observed a rise of the insulin level in peripheral blood as compared with baseline values (p = 0.002). Statistically significant hyperinsulinaemia persisted one month after TIPS (p = 0.005). Values of C-peptide did not change significantly in time, neither in the hepatic vein nor in the peripheral blood. On examination of IR no statistically significant changes occurred after TIPS. On evaluation of different groups of diabetics and non-diabetics the IR was more marked in patients with DM (mean M = 1.7 mg/kg/min.) than in patients without DM (3.7 mg/kg/min.) (p = 0.03). The authors did not record significant changes of IR in time in different groups. Compensation of DM was not influenced by TIPS. The fasting blood sugar levels before TIPS and 1 month after TIPS were comparable.. After TIPS a rise of the insulin level in peripheral blood occurred due to the reduced insulin clearance in the liver. Despite hyperinsulinaemia which persisted for one month after the operation, the insulin resistance did not deteriorate. Compensation of diabetes was not affected by TIPS.

Topics: Adult; Aged; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension, Portal; Insulin; Insulin Resistance; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic

Diabetes mellitus (DM) as part of chronic pancreatitis (ChP) belongs into the group of secondary DM with typical insulin deficiency. The prevalence and incidence of DM in ChP depends on the selected diagnostic criteria, geographical conditions and duration and grade of pancreatitis. Based on our findings during a 15-year investigation of impaired glucose tolerance and insulin secretion in patients with ChP the authors submit some partial (published and unpublished) results. The largest investigated group were 122 patients with ChP diagnosed according to the morphological appearance during ERCP. The authors detected a mutual close relationship between the extent of morphological damage of the efferent system of the pancreas on one hand and impaired glucose metabolism and endogenous insulin secretion on the other hand. It was revealed that values of C-peptide are in patients with ChP and normal glucose tolerance significantly lower as compared with the healthy population, and in patients with ChP and DM they are significantly lower as compared with non-obese type 2 diabetics. With the persistence of ChP the C-peptide levels decline gradually and the incidence of diabetes increases but even when DM persists in ChP C-peptide does not reach zero values as in type 1 DM. For detection of diabetes in ChP assessment of the fasting blood sugar level does not suffice and an oral glucose tolerance test must be made.

Topics: Adult; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatitis, Chronic

This study examined the metabolic effects of heart transplantation in patients in end-stage cardiac failure.. A total of 18 patients after heart transplantation for end-stage heart disease (age 47 +/- 3 years; transplant age 5.5 +/- 1.5 years; BMI 25.8 +/- 0.8 kg/m(2); cyclosporin A 4.2 +/- 0.6 mg/[kg.day]; azathioprine 0.87 +/- 0.31 mg/[kg.day]), 12 patients with type 2 diabetes (D-Tx), and 6 patients without type 2 diabetes (Tx) were studied by means of 1) an oral glucose tolerance test (OGTT) to assess the beta-cell secretory response, 2) a euglycemic-hyperinsulinemic (1 mU/[kg.min]) clamp combined with indirect calorimetry and a primed continuous infusion of [6,6-2H2]glucose and [1-13C]leucine to measure postabsorptive and insulin-stimulated carbohydrate and protein metabolism, and 3) 1H-NMR spectroscopy of the calf muscles to measure intramyocellular triglyceride (IMCL) content. The patients were selected from 480 transplant patients in whom there was a 6% prevalence of type 2 diabetes. Five healthy subjects matched for anthropometric parameters served as control subjects (CON).. Tx had postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism, as well as IMCL content, similar to that of CON. D-Tx were characterized by a reduced secretory response during the OGTT and peripheral insulin resistance with respect to glucose metabolism, which was paralleled by increased plasma free fatty acid concentrations and IMCL content. A defective insulin-dependent suppression of the endogenous leucine flux (index of proteolysis) was also evident during the clamp in D-Tx.. Heart transplantation, notwithstanding the immunosuppressive therapy, was characterized by a normal postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism in Tx. In contrast, insulin resistance with respect to glucose, free fatty acids, and protein metabolism was present in D-Tx regardless of whether diabetes was preexisting or consequent to heart transplantation.

Topics: Adult; Albuminuria; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetic Neuropathies; Energy Metabolism; Female; Follow-Up Studies; Glucagon; Glucose Clamp Technique; Heart Transplantation; Humans; Insulin; Lipids; Male; Middle Aged; Neural Conduction

Even if the pathogenesis of diabetic neuropathy is incompletely understood, an impaired Na/K adenosine triphosphatase (ATPase) activity has been involved in this pathogenesis. We previously showed that a restriction fragment length polymorphism (RFLP) of the ATP1-A1 gene encoding for the Na/K ATPase's alpha 1 isoform is associated with a low Na/K ATPase activity in the red blood cells (RBCs) of type 1 diabetic patients. We thus suggested that the presence of the variant of the ATP1A1 gene is a predisposing factor for diabetic neuropathy, with a 6.5% relative risk. Furthermore, there is experimental evidence showing that lack of C-peptide impairs Na/K ATPase activity, and that this activity is positively correlated with C-peptide level. The aim of this study was to evaluate the respective influence of genetic (ATP1-A1 polymorphism) and environmental (lack of C-peptide) factors on RBC's Na/K ATPase activity. Healthy and diabetic European and North African subjects were studied. North Africans were studied because there is a high prevalence and severity of neuropathy in this diabetic population, and ethnic differences in RBC's Na/K ATPase activity are described. In Europeans, Na/K ATPase activity was significantly lower in type 1 (285 +/- 8 nmol Pi/mg protein/h) than in type 2 diabetic patients (335 +/- 13 nmol Pi/mg protein/h) or healthy subjects (395 +/- 9 nmol Pi/mg protein/h). Among type 2 diabetic patients, there was a significant correlation between RBC's Na/K ATPase activity and fasting plasma C-peptide level (r = 0.32, P <.05). In North Africans, we confirm the ethnic RBC's Na/K ATPase activity decrease in healthy subjects (296 +/- 26 v 395 +/- 9 nmol Pi/mg protein/h, r < 0.05), as well as in type 1 diabetic patients (246 +/- 20 v 285 +/- 8 nmol Pi/mg protein/h; P <.05). However, there is no relationship between the ATP1A1 gene polymorphism and Na/K ATPase activity. ATP1A1 gene polymorphism could not explain the ethnic difference. We previously showed that Na/K ATPase activity is higher in type 1 diabetic patients without the restriction site on ATP1A1 than in those heterozygous for the restriction site. This fact was not observed in healthy subjects. In type 2 diabetic patients, association between ATP1A1 gene polymorphism and decreased enzyme activity was found only in patients with a low C-peptide level. Therefore, the ATP1-A1 gene polymorphism influences Na/K ATPase activity only in case of complete or partial C-peptide deficiency, as observed in

Topics: Adult; Africa, Northern; Black People; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Environment; Erythrocytes; Europe; Female; Humans; Isoenzymes; Male; Middle Aged; Polymorphism, Genetic; Sodium-Potassium-Exchanging ATPase; White People

Diabetes mellitus (DM) is a complication of tacrolimus therapy. This prospective study evaluated the prevalence of DM in South African black and white patients receiving tacrolimus after kidney transplantation and factors that could identify patients before transplantation who may be at risk of developing DM.. Fasting blood samples from 17 patients (11 black, 6 white) were analyzed immediately pretransplantation and at 1 and 3 months posttransplantation for glucose, HbAIC, insulin, C-peptide, free fatty acids, lipids, urea, and creatinine. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) formulas.. Eight patients (47%) became diabetic (six black, two white), and nine patients (five black, four white) remained nondiabetic. Mean glucose concentrations in the diabetic group were significantly higher at 1 month (P=0.03) and 3 months (P=0.01). Mean insulin level was also significantly raised at 3 months (P=0.01) as was HbAIC (P=0.001). C-peptide concentrations did not change significantly in either group. Significant correlations emerged between fasting glucose concentrations at 3 months posttransplantation and initial HOMA (r=0.486; P=0.048) and initial QUICKI (r=-0.582; P=0.014).. Occurrence of DM was high and somewhat greater in black patients. IR was the main mechanism involved, together with inadequate beta-cell compensation. IR pretransplantation predicts the subsequent development of DM.

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glycated Hemoglobin; Homeostasis; Humans; Immunosuppressive Agents; Insulin; Insulin Resistance; Kidney Transplantation; Male; Middle Aged; Models, Biological; Regression Analysis; South Africa; Tacrolimus; Time Factors; White People

Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents.. All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose.. Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance.. Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.

Topics: Adolescent; Black People; Blood Glucose; C-Peptide; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Hispanic or Latino; Humans; Insulin; Insulin Secretion; Male; Obesity; Prevalence; Proinsulin; Risk Factors; White People

Insulin or insulin resistance is considered a coronary heart disease (CHD) risk factor, but proinsulin may have a stronger association with CHD than insulin. The role of sex differences in this association is unclear. We examined the cross-sectional association of proinsulin and insulin with CHD in older men and women without diabetes.. A cross-sectional study of community-dwelling men (n=554) and women (n=902), 50 to 97 years of age, without diabetes by history or oral glucose tolerance test, was done between 1992 and 1996; plasma levels of intact insulin, proinsulin, and C-peptide were measured by radioimmunoassay. Based on questionnaire, medical history, or ECG abnormalities, 25% of men (n=136) and 24% of women (n=214) had prevalent CHD. All insulin variables were positively correlated with CHD risk factors. Compared with those without CHD, men and women with CHD had significantly higher levels of proinsulin. Women but not men with CHD also had higher levels of C-peptide and fasting and postchallenge insulin. Only proinsulin was significantly and independently associated with prevalent CHD in both men (OR=2.41, 1.42 to 4.11) and women (OR=1.80, 1.22 to 2.64) (adjusted for age, body mass index, systolic blood pressure, and HDL cholesterol). Similar analyses for fasting and postchallenge intact insulin and for C-peptide showed that among these three variables, only postchallenge insulin was significantly associated with CHD, and only in women.. In older nondiabetic men and women, proinsulin was more strongly and consistently associated with CHD than was intact insulin.

Topics: Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; C-Peptide; California; Cholesterol, HDL; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus; Electrocardiography; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Odds Ratio; Proinsulin; Radioimmunoassay; Risk Factors; Sex Distribution; Sex Factors; Surveys and Questionnaires; White People

A 30year-old Hispanic male who presented with transient neonatal diabetes mellitus at 4 months has been intensively studied with 12 islet-cell secretagogues from 4 months to 24 years. He was both ICA- and GAD-65-negative, but at 28 years was diagnosed with hypothyroidism due to positive thyroperoxidase antibodies. The course of his disease(s) and the various presentations of hyperglycemia are documented and illustrated by the responses in islet cell hormone secretion, namely, insulin, glucagon, and C-peptide. Insulin secretion gradually fell over 24 years, glucagon secretion persisted from infancy to 24 years but was only minimal during i.v. glucose at 24 years, and C-peptide secretion remained normal, although modest, throughout the 24 years. These data suggest that, despite changing presentations of diabetes mellitus over time, the islets continued to process proinsulin, although the patient required insulin therapy.

Topics: Adult; Arginine; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon; Glucose Tolerance Test; Humans; Infant; Insulin; Insulin Secretion; Islets of Langerhans; Male; Tolbutamide

We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT).. Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si).. ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05).. Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Male; Obesity

First-degree relatives of Type II (non-insulin-dependent) diabetic patients in cross-sectional studies have increased insulin resistance, associated cardiovascular risk factors and abnormalities of fibrinolysis and coagulation. To minimise between-family genetic and environmental confounders, we investigated within-family relationships between early hyperglycaemia and risk factors.. Thirteen age and gender matched sibling pairs of Type II (non-insulin-dependent) diabetic patients, one hyperglycaemic, one normoglycaemic (fasting plasma glucose at screening 6.0-7.7 mmol.l(-1) and < 6.0 mmol.l(-1), respectively) were assessed for plasminogen activator inhibitor antigen (PAI-1), tissue plasminogen activator antigen (t-PA), fibrinogen, Factor VII and Factor VIII/von Willebrand factor antigen. Fasting lipid profiles, blood pressure and HOMA insulin sensitivity (%S) were also measured in siblings and in matched subjects without family history of diabetes.. Hyperglycaemic and normoglycaemic siblings (7 female, 6 male) were aged, mean (SD) 56.8 (8.7) and 55.8 (8.4) years. Hyperglycaemic siblings had increased PAI-1 antigen, geometric mean (i.q.r.): 26.3 (15.1-45.6) vs 11.1 (2.1-23.3) ng/ml, p=0.0002, similar t-PA antigen, mean (SD) 9.5 (4.3) vs 7.4 (2.5) ng/ml, p=0.2 and fibrinogen 2.2 (0.3) vs 2.3 (0.6) g/l, p=0.5, and reduced %S 66.3 (30.5) vs 82.9 (25), p=0.04. PAI-1 correlated negatively with %S ( r=-0.55, p=0.005). No significant differences were found in blood pressure or fasting lipids.. A minor increase in plasma glucose in non-diabetic sibling pairs of Type II (non-insulin-dependent) diabetic patients was associated with reduced insulin sensitivity, increased central adiposity and a doubling of PAI-1 antigen concentration, suggesting impaired fibrinolysis. It is possible that this could contribute to increased cardiovascular risk in these subjects.

Topics: Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Proinsulin; Reference Values; Siblings; Smoking

To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD).. Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT).. Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01).. NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.

Topics: Adult; Aged; Asian; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Japan; Lipids; Male; Middle Aged; Risk Factors; Sensitivity and Specificity

To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n=157) of all incident cases (n=879) 15-34 years old, 1992-1993 in Sweden, and with positivity for at least one autoantibody of islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A) were followed prospectively for the first four years with annual analysis of C-peptide. The aim was to relate the course of beta cell function, measured as C-peptide, in early diabetes with the presence of different islet autoantibodies at diagnosis. We found that patients positive for ICA alone (n=11) had significantly higher C-peptide levels both at diagnosis and during the first three years compared with the other patients (n=146; p=0.022, p<0.001, p=0.004 and p=0.0022). Patients positive for GADA alone or in combination with other antibodies (n=125) had significantly lower C-peptide during the first three years after diagnosis compared with the other patients (n=32, p<0.001, p=0.0011 and p=0.0136). Patients with two or three autoantibodies had C-peptide levels similar to levels found in patients positive only for GADA. However, after four years, there were no significant differences between any of the groups of different autoantibody combinations. At diagnosis, 55% (86/157) of the patients had C-peptide levels above the lower normal range of 0.25 nmol/l, but the frequency of patients with beta cell function above this level decreased after two years to 41% (65/157; p=0.035) and after four years to 22% (35/157; p=0.0041). It is concluded that young adult diabetic patients positive only for ICA at diagnosis have a better preserved beta cell function with higher levels of C-peptide during the first three years compared with patients positive for GADA alone or in combinations with other autoantibodies.

Topics: Adolescent; Adult; Autoantibodies; Autoantigens; Biomarkers; C-Peptide; Diabetes Mellitus; Follow-Up Studies; Humans; Islets of Langerhans; Membrane Proteins; Prospective Studies; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Sweden

Topics: Amine Oxidase (Copper-Containing); C-Peptide; Diabetes Mellitus; Heart Failure; Humans; Insulin; Kinetics; Reference Values

Defects in hepatic insulin action in type 2 diabetes and its possible underlying mechanisms were assessed in euglycemic-hyperinsulinemic clamp studies, using improved tracer methods (constant specific activity technique). Ten obese diabetic patients (age 54 years, BMI 29 +/- 0.5 kg/m(2)) and ten matched control subjects were studied at baseline (after an overnight fast) and during insulin infusions of 20- and 40-mU. m(-2). min(-1). In the diabetic patients, plasma glucose levels were normalized overnight before the studies by low-dose insulin infusion. Hepatic sinusoidal insulin levels were estimated, and plasma levels of free fatty acids (FFAs) and glucagon were determined to assess the direct and indirect effects of insulin on hepatic glucose production (HGP) in type 2 diabetes. Baseline rates of HGP (86 +/- 3 vs. 76 +/- 3 mg. m(-2). min(-1), P < 0.05) were slightly elevated in the diabetic patients compared with control subjects, despite much higher hepatic sinusoidal insulin levels (26 +/- 3 vs. 12 +/- 2 mU/l, P < 0.001). Consequently, a marked defect in the direct (hepatic) effect of insulin on HGP appeared to be present at low insulin levels. However, in response to a small increase in baseline hepatic sinusoidal insulin levels of 11 mU/l (26 +/- 3 to 37 +/- 3 mU/l, P < 0.05) in the 20-mU clamp, a marked suppression of HGP was observed in the diabetic patients (86 +/- 3 to 32 +/- 5 mg. m(-2). min(-1), P < 0.001), despite only minimal changes in FFAs (0.33 +/- 0.05 to 0.25 +/- 0.05 mmol/l, NS) and glucagon (14 +/- 1 to 11 +/- 2 pmol/l, P < 0.05) levels, suggesting that the impairment in the direct effect of insulin can be overcome by a small increase in insulin levels. Compared with control subjects, suppression of HGP in the diabetic patients was slightly impaired in the 20-mU clamp (32 +/- 5 vs. 22 +/- 4 mg. m(-2). min(-1), P < 0.05) but not in the 40-mU clamp (25 +/- 2 vs. 21 +/- 3 mg. m(-2). min(-1), NS). In the 20-mU clamp, hepatic sinusoidal insulin levels in the diabetic patients were comparable with control subjects (37 +/- 3 vs. 36 +/- 3 mU/l, NS), whereas both FFA and glucagon levels were higher (i.e., less suppressed) and correlated with the rates of HGP (R = 0.71, P < 0.02; and R = 0.69, P < 0.05, respectively). Thus, at this insulin level impaired indirect (extrahepatic) effects of insulin seemed to prevail. In conclusion, hepatic insulin resistance is present in obese type 2 diabetic patients but is of quantitative significance only at

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Tolerance Test; Humans; Insulin; Liver; Middle Aged; Obesity

To determine prevalence estimates in order to monitor diabetes, particularly type 2 diabetes, in American Indian youth.. To explore the feasibility of developing a case definition using information from primary care records, all youth aged <20 years with an outpatient visit or hospitalization for diabetes were identified from the Billings Area Indian Health Service database in Montana and Wyoming from 1997 to 1999, and the medical records were reviewed. Classification for probable type 1 diabetes was based on age < or =5 years, weight per age < or =15th percentile at diagnosis, or positive results of islet cell antibody test. Classification for probable type 2 diabetes was based on weight per age > or =85th percentile or presence of acanthosis nigricans at diagnosis, elevated C-peptide or insulin, family history for type 2 diabetes, or use of oral hypoglycemic agents with or without insulin or absence of current treatment 1 year after diagnosis.. A total of 52 case subjects with diabetes were identified, 3 of whom had diabetes secondary to other conditions. Of the remaining 49 case subjects, 25 (51%) were categorized as having probable type 2 diabetes, 14 (29%) as having probable type 1 diabetes, and 10 (20%) could not be categorized because of missing or negative information. Prevalence estimates for diabetes of all types, type 1 diabetes, and type 2 diabetes were 2.3, 0.6, and 1.1, respectively, per 1,000 youth aged <20 years.. Our definitions may be useful for surveillance in primary care settings until further studies develop feasible case definitions for monitoring trends in diabetes among youth.

Topics: Acanthosis Nigricans; Adolescent; Adult; Autoantibodies; Body Weight; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Guidelines as Topic; Humans; Indians, North American; Inpatients; Insulin; Islets of Langerhans; Medical Records; Montana; Outpatients; Retrospective Studies; Wyoming

We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. Five types of diabetes were delineated: Type 1 (37%), ketosis resistant (32%), Type 2 (13%), fibrocalculous pancreatopathy (11%) and autoimmune polyglandular syndrome (7%). C-peptide response to glucagon was assessed in a representative subset of 50 patients with Type 1, ketosis resistant, and autoimmune polyglandular syndrome. A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. Type 1 showed significantly less C-peptide response to glucagon when compared to the ketosis resistant and autoimmune polyglandular syndrome groups. The controls and Type 2 diabetic individuals tested negative for islet cell autoimmunity markers. These findings demonstrate a role of islet cell autoimmunity in the pathogenesis of four out of the five clinical types of youth onset diabetes seen in North India.

Topics: Adolescent; Adult; Age of Onset; Asian People; Autoantibodies; C-Peptide; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Glutamate Decarboxylase; Humans; India; Islets of Langerhans; Isoenzymes; Male; Pancreatic Diseases; Thyroid Gland

The conventional dosage of hydrocortisone, used for many years in the management of hypopituitarism (30 mg per day), has now been shown to be more than is physiologically necessary. On this conventional corticosteroid therapy studies have demonstrated an increased prevalence of diabetes and impaired glucose tolerance, which may contribute to the increased vascular morbidity and mortality reported in the condition. In these studies no information is available on oral glucose tolerance test (OGTT) timing in relation to administration of oral steroid and variable hydrocortisone doses were employed.. In order to assess glucose tolerance in patients treated with lower, more physiological doses, we performed a 75-g OGTT at least 1 month after hydrocortisone therapy was adjusted to 15 mg at 0800 h and 5 mg at 1700 h in 45 adult onset hypopituitary patients (30 M, 15 F). Mean (+/- SD) duration of hypopituitarism was 12 +/- 10 years, mean age 52 +/- 14 years and BMI 29.3 +/- 5.1 kg/m2. All were on hydrocortisone, 43 on thyroxine, 31 on sex steroids, 9 on desmopressin and 33 had documented growth hormone deficiency. Hydrocortisone 15 mg was taken at 0800 and the OGTT commenced at 0900.. Using standard WHO criteria 36 patients (80%) had normal glucose tolerance, 1 (2%) had newly diagnosed diabetes and 8 (18%) had impaired glucose tolerance. Using the recently announced American Diabetes Association criteria for diagnosis 96% had normal glucose tolerance, 2% had diabetes and 2% impaired fasting glucose.. The markedly reduced prevalence of diabetes and impaired glucose tolerance on lower hydrocortisone replacement doses in our series of patients with hypopituitarism, not previously known to be diabetic, is of great interest. This lower prevalence may eventually result in reduced vascular complication rates.

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Hypopituitarism; Insulin; Male; Middle Aged; Statistics, Nonparametric

The influence of the hormones most involved in glucose homeostasis, C-peptide, insulin and glucagon on blood viscosity was tested in vitro. Whole blood (adjusted to haematocrit 45%) from healthy volunteers (n=24) and patients with diabetes mellitus (n=17) was incubated with 10(-7)-10(-10) M C-peptide, insulin or glucagon. None of these peptide hormones, neither at physiological nor at supraphysiological levels, had an influence on high (94.5 s(-1)) or low (0.1 s(-1)) shear rate viscosity. The small group of diabetic patients had a higher plasma viscosity and increased blood viscosity at 94.5 s(-1), which is in agreement with earlier studies, but decreased viscosity at low shear rate. We conclude that C-peptide, insulin and glucagon have no direct effect on blood viscosity in vitro. It is, therefore, unlikely that microvascular disturbances seen with either deficiency or excess of these hormones is due to haemorheological factors.

Topics: Adult; Aged; Blood Proteins; Blood Viscosity; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Erythrocyte Indices; Female; Glucagon; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged

The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes.. The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test.. The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099).. This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Deafness; Diabetes Complications; Diabetes Mellitus; DNA, Mitochondrial; Female; Genomic Imprinting; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Nuclear Family; Pedigree; Point Mutation; Reference Values; RNA; RNA, Mitochondrial; RNA, Transfer, Leu; Time Factors

Abnormalities observed in intermediary metabolism may be related to the pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and lactate production was estimated in the sc adipose tissue of two anatomical regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban women. This was done with the sc microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance. Biochemical measurements were made in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used to define body composition. DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P < 0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/- 0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate levels increased across the three groups (LW < OW < DW). During the oral glucose tolerance test, glucose levels were elevated in DW, with higher insulin levels [0 h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW, 320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932 +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW, 1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3 mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2 micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)]. By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW, 1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001); femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR was appropriately low for body fat mass in LW, with a brisk increase between 0 and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting lipolytic rate is associated with insulin levels;

Topics: Adipose Tissue; Adult; Black People; Body Composition; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Food; Glucose Tolerance Test; Glycerol; Humans; Lactic Acid; Obesity; South Africa; Testosterone; Urban Population

Impaired glucose tolerance and diabetes mellitus have been associated with a prolonged QT interval among select populations. However, these associations remain unclear among the general population.. We examined these relationships using data from 5833 adults aged 40-90 years from NHANES III (1988-1994). Univariate differences in cardiovascular disease (CVD) risk factors were examined across tertiles of heart rate corrected QT (QTc). The association between glucose intolerance, CVD risk factors and a prolonged QTc (> or = 0.440 s) was also assessed with logistic regression adjusting for age, race, gender, education, and heart rate.. Prolonged QTc was observed among 22.0% of persons with normal glucose tolerance (NGT), 29.9% of those with impaired fasting glucose (IFG), and among 42.2% of persons with diabetes. Hypertension, serum cholesterol, obesity, heart rate, and fasting C-peptide and serum insulin levels were associated with prolonged QTc (all: P < or = 0.05). After multivariate adjustment, persons with IFG were 1.2 times (95% CI=0.7-2.0) as likely and persons with diabetes 1.6 times (95% CI=1.1-2.3) as likely to have a prolonged QTc as persons with NGT. In addition, persons with diabetes and two or more additional CVD risk factors were 2.3 times (95% CI=1.3-4.0) as likely to have a prolonged QTc as persons with NGT and no CVD risk factors after multivariate adjustment.. Diabetes was associated with an increased likelihood of prolonged QTc independent of age, race, gender, education, and heart rate. In addition, persons with diabetes and multiple CVD risk factors were more likely to have a prolonged QTc than those with NGT and no additional risk factors, suggesting that these persons may be at increased risk for cardiac arrhythmia and sudden death.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Electrocardiography; Female; Glucose Intolerance; Health Surveys; Heart Diseases; Humans; Insulin; Male; Middle Aged; Multivariate Analysis; Risk Factors

The aim of our study was to estimate the serum levels of glucose, insulin, C-peptide and uric acid in patients with psoriasis before and after treatment. The study included 12 males with active form of psoriasis and 15 control subjects carefully matched to the psoriatic patients for age and BMI. All measured parameters were in patients with psoriasis significantly increased and dependent on the BMI. Compared with pretreatment values of glucose and uric acid were significantly lower during therapy. The increase in the mean C-peptide and insulin levels after psoriasis therapy was constant and independent from clinical stage of disease. The results of the present study have provided evidence for the importance of impaired glucose and purine metabolism in patients with psoriasis in the increase risk of development of diabetes mellitus and hypertension.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Diabetes Mellitus; Humans; Hypertension; Insulin; Male; Middle Aged; Psoriasis; Risk; Treatment Outcome; Uric Acid

Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the beta-cell function and an insulin clamp combined with [3-(3)H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (P <.05) and insulin deficiency during the OGTT (P <.05). Liver transplantation normalized endogenous glucose production and insulin sensitivity but failed to cure diabetes in 8 of the 24 patients because a markedly low insulin response during the OGTT. Age, body mass index, family history of diabetes, immunosuppressive drugs, and pathogenesis of cirrhosis did not predict in whom liver transplant was going to cure diabetes. On the contrary, a reduced secretory response characterized the patients in whom the transplant would not be curative. In summary, insulin resistance was a primary event complicating cirrhosis but additional beta-cell secretory defects were crucial for development of diabetes. Liver transplantation, lessening insulin resistance, cured hepatogenous diabetes in 67% of cirrhotic-diabetic patients; nevertheless 33% were still diabetics because the persistence of a reduced beta-cell function, which makes these patients eventually eligible for combined islet transplantation.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Carcinoma, Hepatocellular; Diabetes Complications; Diabetes Mellitus; Follow-Up Studies; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Middle Aged

Alcohol intake can have hypoglycemic or hyperglycemic effects in patients with type 2 diabetes mellitus. The present study was designed to investigate the glycemic control of male patients with diabetes mellitus from the aspect of the genetic status of alcohol metabolism.. One hundred sixty-three men with type 2 diabetes mellitus were enrolled in the present study. They were all outpatients at the Diabetes Center of Saiseikai Central Hospital. The genotype of the aldehyde dehydrogenase 2 (ALDH2) gene of each patient was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the patients were divided into those with active or inactive ALDH2 phenotype. We compared the amount of habitual alcohol intake and clinical data that included physical findings and blood chemistry of the patients in the active and inactive ALDH2 groups. The glycemic control of each patient was evaluated by the serum level of HbAlc.. Of the 163 patients with type 2 diabetes mellitus, 90 patients had the active ALDH2 phenotype and 73 patients had the inactive ALDH2 phenotype. The mean HbA1c level of the active ALDH2 group was nearly the same as that of the inactive ALDH2 group. However, the HbA1c level of the light-to-moderate drinkers (1-400 g/week) in the inactive ALDH2 group was highest and was significantly higher than the HbA1c level of the light-to-moderate drinkers of the active ALDH2 group. The HbA1c of the patients with diabetic complications was higher than the HbAlc of those without diabetic complications in both the active and inactive ALDH2 groups. However, the HbA1c level of the light-to-moderate drinkers without diabetic complications in the inactive ALDH2 group was significantly higher and the incidence of 24 hr urinary C-peptide was higher than the respective level of the light-to-moderate drinkers without diabetic complications in the active ALDH2 group.. Habitual light-to-moderate alcohol intake worsens glycemic control in diabetic patients who have the inactive ALDH2 phenotype. The data on 24 hr urinary C-peptide level suggested that increased acetaldehyde after light-to-moderate drinking by inactive ALDH2 diabetic patients may increase the HbA1c value by the insulin-resistant condition that resulted in hyperinsulinemia.

Topics: Adult; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Ethanol; Genotype; Glycated Hemoglobin; Humans; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

To determine whether atypical diabetes mellitus (ADM) is present in the Chinese population in Hong Kong.. The records of Chinese patients who attended the Diabetes Clinic at Queen Mary Hospital were reviewed. We identified 11 patients who initially presented with acute diabetic ketoacidosis but subsequently displayed clinical features more typical of type 2 diabetes. Metabolic studies and HLA typing were performed to characterize this group of Chinese patients with ADM.. C-peptide response of the patients with ADM 1 h after a standard meal was intermediate between that of type 1 diabetic patients (matched for age and duration of diabetes) and that of nondiabetic control subjects (matched for age and BMI) (analysis of variance, P = 0.02). Insulin sensitivity measured by a short insulin tolerance test was not significantly different between patients with ADM and their matched nondiabetic control subjects. HLA typing showed that none of the patients with ADM had the DR3 allele and that the frequency of DR9 was not increased. Only one patient had significantly increased levels of antibodies to GAD and islet cell antigen 512.. ADM, which was first described in African-Americans, is seen also in Chinese subjects. These patients have significant residual C-peptide secretory capacity and should not be misdiagnosed and treated as patients with type 1 diabetes with life-long insulin therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; C-Peptide; China; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Histocompatibility Testing; HLA-DR3 Antigen; Hong Kong; Humans; Insulin; Male; Middle Aged; Retrospective Studies

Topics: Aged; C-Peptide; Diabetes Complications; Diabetes Mellitus; Disease Progression; Follicle Stimulating Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Male; Orchiectomy; Progesterone; Prostatic Neoplasms

We investigated twenty-one insulin-using patients, who had all been labelled as having insulin dependent diabetes mellitus (IDDM) or type 1 diabetes. Physicians have been erroneously using the term IDDM loosely to include all diabetics on insulin. The clinical criteria of the National Diabetes Data Group/WHO were used to reclassify these patients. Only thirteen were found to have IDDM and eight non-insulin dependent diabetes mellitus (NIDDM). Using fasting C-peptide values, only five of the thirteen with clinical IDDM truly had IDDM, the others might have maturity onset diabetes of the young (MODY) or diabetes in the young. Of the eight with clinical NIDDM seven had normal to high C-peptide values; the lone patient with low C-peptide values had diabetes diagnosed at age 64 years. We conclude that the clinical classification of diabetes mellitus may be inaccurate and that C-peptide evaluation improves the accuracy of the classification.

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diagnostic Errors; Female; Humans; Insulin; Male; Middle Aged; Prevalence

This study investigated the association between glutamic acid decarboxylase antibodies (GAD-AB) and Type 1, Type 2, pancreatic and lipoatrophic diabetes mellitus (DM) in South African patients.. Four groups were selected: group A, 100 Black Type 1 DM patients (age at onset < 35 years, body mass index (BMI) < 27 kg/m2 and insulin dependent within 1 year of presentation); group B, 80 Black Type 2 DM patients (age at onset > 35 years, BMI > 27 kg/m2 and controlled on oral hypoglycaemic agents for at least 1 year after presentation); group C, 10 patients of varying ethnicity with DM or impaired glucose tolerance secondary to chronic pancreatitis; group D, five patients of varying ethnicity with DM associated with total lipodystrophy. Fifty healthy Black control subjects were also studied (group E). Serum GAD-AB and random C-peptide levels were measured by radioimmunoassay.. Mean C-peptide concentration was significantly lower in Type 1 DM patients than Type 2 DM patients (P < 0.00001). Forty-four patients with Type 1 DM were GAD-AB-positive compared to two patients with Type 2 DM. Two control subjects were also GAD-AB-positive. No patient in the other groups had a titre > 1 U/ml. Type 1 DM patients who were GAD-AB-positive did not differ from those who were GAD-AB-negative for age at onset, duration of DM or C-peptide concentrations.. Auto-immune beta-cell destruction has an important role in the pathogenesis of Type 1 DM amongst African patients. However, Type 2 African DM patients and other diabetes subtypes are largely GAD-AB-negative.

Topics: Adult; Autoantibodies; Black People; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Male; Middle Aged; Pancreatic Diseases; Radioimmunoassay; South Africa

Studies on pathogenesis of neonatal diabetes may lead to better understanding of pancreatic beta-cell maturation and regulation of insulin secretion. The purpose of this study was to examine the clinical course, immunologic and genetic background of the transient and permanent form of neonatal diabetes. Clinical data (onset and duration of diabetes, C peptide levels, duration of insulin treatment, associated disorders) were collected, islet cell specific antibodies (islet cell antibody and glutamate decarboxylase antibody) were determined and genetic analyses (HLA DQA1-DQB1 typing and microsatellite mapping on chromosome 6) were performed in three patients with permanent and three patients with transient neonatal diabetes. None of the six patients had HLA DQ diabetes susceptibility alleles and most infants were negative for islet cell autoantibodies indicating that no pancreatic islet-cell specific autoimmunity exists in the two forms of neonatal diabetes mellitus. Complete paternal uniparental isodisomy of chromosome 6 has been identified in a transient neonatal diabetes case with macroglossia. The permanent neonatal diabetes cases and the other two cases with transient form did not possess this chromosome anomaly. It is concluded, that none of the two forms neonatal diabetes is of autoimmune origin. They have different genetic background and represent different disease entities. Transient neonatal diabetes is probably caused by alteration of expression of an imprinted gene on chromosome 6 which might play role in fetal growth and pancreatic beta-cell maturation and insulin secretion. Permanent neonatal diabetes is probably a more heterogenous phenotype, the cause of which remains to be clarified in the future.

Topics: Autoantibodies; C-Peptide; Chromosomes, Human, Pair 6; Diabetes Mellitus; Female; Gene Expression Regulation; Glutamate Decarboxylase; HLA-DQ Antigens; Humans; Infant, Newborn; Islets of Langerhans; Male; Microsatellite Repeats

To determine whether hormone replacement therapy (HRT) alters glucose metabolism.. Cross-sectional data from the third National Health and Nutrition Examination Survey (1988-1994) included levels of hemoglobin A(1c) in women with diagnosed diabetes and levels of hemoglobin A(1c), fasting and 2-hour glucose, and fasting insulin and C-peptide in women without diagnosed diabetes. We compared mean values for these measures among never, current, and past users of HRT with adjustment for confounders. Types of hormones were not studied.. Hormone replacement therapy was used by 8. 6% of diabetic women and 16.7% of women without diagnosed diabetes; 19.3% and 18.5%, respectively, had used HRT in the past. Current use approximately doubled among diabetic women between 1988-1991 and 1991-1994. Current users had lower hemoglobin A(1c) and fasting plasma glucose levels but higher 2-hour glucose levels compared with never and past users. After adjustment for confounding factors, hemoglobin A(1c) levels were 0.1% lower, fasting glucose levels were 3 mg/dL lower, and 2-hour glucose levels were 15 mg/dL higher in current users. Fasting serum insulin and C-peptide levels were not associated with HRT use. Duration of HRT use among current users and time since cessation among former users were not associated with measures of glucose metabolism.. The prevalence of HRT in the United States among diabetic women is approximately half that of women without diabetes diagnoses, although it appears to be increasing. Postmenopausal hormones appear to have no adverse effect on basal glucose metabolism but are associated with slightly elevated postchallenge glucose levels.

Topics: Aged; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Hormone Replacement Therapy; Humans; Insulin; Middle Aged; Nutrition Surveys; Time Factors; United States

Topics: Adult; Antiviral Agents; C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; HIV Infections; HIV-1; Humans; Hyperglycemia; Insulin; Male; Protease Inhibitors

Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester.. Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma.. Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin.. These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Topics: Acanthosis Nigricans; Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Glycosuria; Humans; Hyperglycemia; Hypoglycemic Agents; India; Insulin; Insulin Resistance; Obesity; Pakistan; Saudi Arabia; United Kingdom

To clarify whether random C-peptide is a valuable test in the classification of diabetes.. All C-peptide measurements conducted in the diabetic population of Skaraborg (280,539 inhabitants and 3.2% diabetes) between 1995 and 1998 (3,115 samples) were considered, but only patients with well-defined diabetes type (1,449 samples from 1,093 patients) were analyzed for the correlation between diabetes type and C-peptide concentration. Serum C-peptide was measured after fasting over night (fCP), after glucagon stimulation (gCP), and randomly (rCP) without considering previous meals at an ordinary visit to the diabetic clinic (rCP). Receiver Operating Characteristic (ROC) curves were constructed to illustrate the power of the different C-peptide protocols and to determine the optimal cut-off values.. Although all three tests had high discriminative power, the ROC curves demonstrated that rCP was superior to fCP and gCP in discriminating type 1 from type 2 diabetes. The optimal cut-off value for rCP was 0.50 nmol/L, for fCP 0.42 nmol/L, and for gCP 0.60 nmol/L.. rCP is more powerful than fCP and gCP in distinguishing type 1 from type 2 diabetes and can therefore be recommended as a classification tool, particularly in outpatients.

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Humans; Middle Aged; Retrospective Studies; ROC Curve

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.

Topics: Blood Glucose; C-Peptide; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Obesity; Thiazoles; Thiazolidinediones; Troglitazone; Tumor Necrosis Factor-alpha

The principal metabolic effect of metformin-an oral antihyperglycaemic agent-is the improvement in the sensitivity of peripheral tissues and liver to insulin. This study examined the effect of metformin monotherapy on antioxidative defence system activity in erythrocytes and plasma in diabetic patients. We studied the effect of metformin treatment on the activities of Cu, Zn-superoxide dismutase (EC 1. 15. 1. 1.), catalase (EC 1. 11. 1. 6.) and glutathione peroxidase (EC 1. 11. 1. 9.) in relation to lipid peroxidation products and reduced glutathione level in plasma and erythrocytes. In this study we also examined erythrocytes' susceptibility to H2O2-induced oxidative stress during metformin therapy. Although metformin monotherapy ameliorated the imbalance between free radical-induced increase in lipid peroxidation (by reducing the MDA level in both erythrocytes and plasma) and decreased plasma and cellular antioxidant defences (by increasing the erythrocyte activities of Cu, Zn, SOD, catalase and GSH level) and decreased erythrocyte susceptibility to oxidative stress, it had negligible effect to scavenge Fe ion-induced free radical generation in a phospholipid-liposome system.

Topics: Blood Glucose; C-Peptide; Catalase; Diabetes Mellitus; Diabetes Mellitus, Type 2; Erythrocytes; Fructosamine; Glutathione; Glutathione Peroxidase; Humans; Hydrogen Peroxide; Hypoglycemic Agents; In Vitro Techniques; Lipid Peroxidation; Metformin; Middle Aged; Obesity; Oxidative Stress; Reference Values; Superoxide Dismutase

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Topics: Albuminuria; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertriglyceridemia; Insulin; Male; Middle Aged; Obesity; Risk Factors

Type 2 diabetes is a heterogeneous disease in which both beta-cell dysfunction and insulin resistance are pathogenetic factors. Disproportionate hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type 2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or insulin resistance may result in secretion of immature beta-cell granules with a higher content of intact proinsulin.. We investigated the impact of obesity on beta-cell secretion in normal subjects and in type 2 diabetic patients by measuring intact proinsulin, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects.. Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4 vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon stimulation, PIM levels were disproportionately elevated (PIM/intact insulin based on area under the curve analysis) in diabetic patients (LD vs. LC and OD vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P < 0.05. Intact insulin and C-peptide net responses were significantly reduced in type 2 diabetic patients, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/- 3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05.. Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.

Topics: Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Obesity; Proinsulin; Radioimmunoassay

The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes.. An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis.. The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups.. The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.

Topics: C-Peptide; Case-Control Studies; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis; Peptide Fragments; Protein Precursors; Time Factors

In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients.. A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis.. A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients.. Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

Topics: Adult; Autoantibodies; Blood Glucose; Body Mass Index; C-Peptide; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Genotype; HLA-DQ alpha-Chains; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Incidence; Islets of Langerhans; Italy; Male; Middle Aged; Thinness

To determine factors predicting hospitalization in people with diabetes.. Two population-based groups with diabetes were examined at baseline (1980-1982), 4 years (1984-1986), and 10 years (1990-1992). The younger-onset group (n = 777) consisted of all persons diagnosed as having diabetes before age 30 years who were taking insulin, and the older-onset group (n = 542) consisted of a sample of persons diagnosed after age 30 years. At the 10-year examination, participants were asked if they had been hospitalized in the previous year. Factors from the 4-year examination were examined for their ability to predict hospitalization at the 10-year examination.. In the younger-onset group, 25.5% reported being hospitalized. In logistic models, glycosylated hemoglobin level (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.16-1.39 for a 1% increment) and hypertension (OR, 1.60; 95% CI, 1.08-2.38) predicted hospitalization. Factors that were not significant included age, sex, systolic and diastolic blood pressures, body mass, smoking status, and alcohol consumption. In the older-onset group, 30.8% reported being hospitalized. In logistic models, only glycosylated hemoglobin level (OR, 1.16; 95% CI, 1.06-1.29 for a 1% increment) predicted hospitalization.. Glycemic control is subject to intervention. Better control may decrease hospitalization among people with diabetes. Thus, there is considerable potential for reducing health care costs.

Topics: Adult; Age of Onset; Aged; Alcohol Drinking; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Complications; Diabetes Mellitus; Exercise; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypertension; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Sex Factors; Smoking

This pilot study was initiated to evaluate factors controlling glucose tolerance in patients with hepatitis C virus-induced liver disease before and after therapy with recombinant interferon-alpha (r-INF-alpha). Fifteen patients with histologically and serologically proven hepatitis C infection underwent oral and frequently sampled intravenous glucose tolerance tests (FSIGTT) before and after four months of therapy (6 x 106 U r-INF-alpha, subcutaneously, three times a week). Glucose, insulin and C-peptide data from FSIGTT were analysed using the minimal modeling technique to determine insulin sensitivity, glucose effectiveness and first and second phase insulin secretion. According to the WHO criteria 13 patients, had normal glucose tolerance; diabetes mellitus was diagnosed in 2 patients. In the morning following the last r-INF-alpha injection four months later, insulin sensitivity improved significantly in hepatitis C virus-infected patients with normal glucose tolerance (2.17 +/- 0.37 vs. 6.18 +/- 0.94 10(-4) min(-1) per microU/ml, p < 0.001) and with diabetes mellitus (0.86 to 2.61; 0.46 to 1.06 10(-4) min(-1) per microU/ml). This effect was independent of the extent of fibrosis, virus load before treatment and therapy response. First phase insulin secretion increased in non-diabetic (139.2 +/- 17.1 vs. 200.0 +/- 32.7, p < 0.05) and diabetic patients with HCV infection (55.24 to 118.5; 84.23 to 261.1). Moreover, free fatty acid concentrations in all HCV-infected patients were significantly reduced (0.48 +/- 0.01 vs 0.21 +/- 0.03 mmol/l, p < 0.01). Therapy with recombinant interferon-alpha is associated with an amelioration of glucose tolerance in non-diabetic and diabetic HCV-infected patients.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Complications; Diabetes Mellitus; Fatty Acids, Nonesterified; Glucose Tolerance Test; Glycated Hemoglobin; Hepacivirus; Hepatitis C; Hepatitis, Autoimmune; Humans; Insulin; Interferon Type I; Kinetics; Pilot Projects; Recombinant Proteins

To determine whether leptin secretion is impaired in diabetes, we compared basal and stimulated plasma leptin levels in diabetic subjects and healthy controls.. Blood samples for assay of leptin and other hormones were obtained at baseline in 54 diabetic patients and 65 controls, and 8 hours, 16 hours, and 40 hours following ingestion of dexamethasone (4 mg) in 6 healthy and 12 controls. C-peptide status was defined as "negative" if < or =0.1 ng/mL or "positive" if > or =0.3 ng/mL, in fasting plasma.. Basal plasma leptin levels were 19.7+/-2.2 ng/mL in nondiabetic subjects, 13.4+/-1.5 ng/ml in C-peptide negative (n = 28) and 26.1+/-3.7 ng/mL in C-peptide positive (n = 26, p = 0.001) diabetic patients. Dexamethasone increased leptin levels of controls (n = 6) to 145+/-17% of baseline values at 8 hours (p = 0.03), 224+/-18% at 16 hours (p = 0.01), and 134+/-18% at 40 hours (p=0.05). The corresponding changes were 108+/-13%, 126+/-23%, and 98+/-16% in C-peptide negative (n=6), and 121+/-10%, 144+/-16% (p=0.03), and 147+/-23% (p=0.11) in C-peptide positive (n = 6) diabetic patients, respectively. The peak stimulated leptin levels were lower in the diabetic patients, compared with controls. Plasma insulin increased (p = 0.02) in controls, but not in the diabetic patients, following dexamethasone.. Although diabetic patients have normal plasma leptin levels under basal conditions, their leptin responses to glucocorticoid are impaired, probably because of the concomitant insulin secretory defect. A subnormal leptin secretory response could worsen obesity and insulin resistance in diabetes.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Dexamethasone; Diabetes Mellitus; Female; Glucocorticoids; Humans; Insulin; Leptin; Male; Middle Aged; Reference Values

Topics: Aged; C-Peptide; Chromans; Diabetes Mellitus; Female; Glucocorticoids; Humans; Hypoglycemic Agents; Polymyositis; Thiazoles; Thiazolidinediones; Troglitazone

To investigate the late sequellae of necrotizing pancreatitis on the endocrine function of the pancreas.. Twenty patients, 15 men (mean +/- SEM age 52.2+/-2.6 years and BMI 26.8+/-0.8 kg/m2) and 5 women (age 51.0+/-7.6 years and BMI 26.7+/-0.8 kg/m2) were submitted to a glucagon stimulation test 63 (range 8-136) months after an attack of pancreatitis. All nondiabetic patients (n = 15) were also submitted to an oral glucose tolerance test. For comparison, 16 healthy volunteers, 8 men (age 56.0+/-0.9 years and BMI 26.3+/-0.4 kg/m2) and 8 women (age 50.5+/-1.0 years and BMI 28.2+/-0.6 kg/m2), were also studied.. Five patients (25%) had diabetes mellitus and needed insulin treatment, 6 patients (30%) had an impaired glucose tolerance (IGT). Nondiabetic patients (IGT included) had a significantly higher basal insulin level (15.8+/-1.9 vs. 10.9 +/-2.2 mU/l, p < 0.05) and a lower glucose/insulin ratio (p < 0.05) compared with controls. The serum concentrations of insulin and C peptide, after stimulation with glucagon, calculated as peak value, maximal increment and as area under the curve were not significantly different in the nondiabetic patients compared to controls. The subgroup of IGT patients had a significantly higher basal C peptide (p < 0.05) and a reduced maximal increment (p < 0.05).. After nonresectional therapy for necrotizing pancreatitis, there is a high prevalence of disturbances in glucose metabolism. Patients with IGT have signs of both loss of beta-cell function and insulin resistance.

Topics: C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Postoperative Complications

The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001).. Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio.. In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Topics: Administration, Oral; Adult; Age Factors; Aged; Albuminuria; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Comorbidity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Italy; Male; Middle Aged; Obesity; Prevalence; Risk Factors

Fibrocalculous pancreatic diabetes (FCPD) is a type of diabetes secondary to tropical chronic non-alcoholic pancreatitis. Little is known about the aetiopathogenesis of FCPD. We studied glutamic acid decarboxylase antibodies (GAD-Ab) and islet cell antibodies (ICA) in patients with FCPD and compared the results with Type 1 (insulin dependent) diabetes mellitus, Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic subjects in Southern India. The prevalence of GAD-Ab was 7.0% (95% Confidence Interval (CI) 1.9-17.2) in FCPD, 47.5% (CI 31.4-64.0) in Type 1 (p < 0.001 compared to FCPD), 5.6% (CI 1.5-13.9) in Type 2 (non-significant (NS) compared to FCPD) and 0% in controls. The prevalence of ICA was 6.3% (CI 1.2-17.4) in FCPD, 53.8% (CI 37.1-70.0) in Type 1 (p < 0.001 compared to FCPD), 9.9% (CI 4.0-19.4) in Type 2 (NS compared to FCPD) and 4.7% (CI 0.4-16.1) in controls. The data suggest that in FCPD, the frequency of auto-antibodies is low and its aetiology is probably not linked to autoimmunity in the majority of the patients.

Topics: Adult; Autoantigens; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; India; Islets of Langerhans; Male; Middle Aged; Pancreatic Diseases; Pancreatitis; Reference Values

Insulin secretion is increased in cirrhotic patients without diabetes but decreased in cirrhotic patients with diabetes. Increased glucagon secretion is found in both groups. Our aim was to determine: 1) whether alterations in insulin secretion are due to changes in maximal secretory capacity or altered islet B-cell sensitivity to glucose, and 2) whether regulation of glucagon secretion by glucose is disturbed.. Insulin, C-peptide and glucagon levels were measured basally and during 12, 19 and 28 mmol/l glucose clamps, and in response to 5 g intravenous arginine basally and after 35 min at a glucose of 12, 19 and 28 mmol/l in 6 non-diabetic alcoholic cirrhotic patients, six diabetic alcoholic cirrhotic patients and six normal controls.. Fasting insulin, and C-peptide levels were higher in cirrhotic patients than controls but not different between diabetic and non-diabetic patients. C-peptide levels at t=35 min of the clamp increased more with glucose concentration in non-diabetic cirrhotic patients than controls; there was little increase in diabetic cirrhotic patients. At a blood glucose of approximately 5 mmol/l the 2-5 min C-peptide response to arginine (CP[ARG]) was similar in all groups, but enhancement of this response by glucose was greater in non-diabetic cirrhotic patients and impaired in diabetic cirrhotic patients. Maximal insulin secretion (CP(ARG) at 28 mmol/l glucose) was 49% higher in the non-diabetic cirrhotic patients than controls (p<0.05); in diabetic cirrhotic patients it was 47% lower (p<0.05). The glucose level required for half-maximal potentiation of (CPARG) was not different in the three groups. Cirrhotic patients had higher fasting glucagon levels, and a greater 2-5-min glucagon response to arginine, which was enhanced by concomitant diabetes (p<0.001 vs controls). Suppression of plasma glucagon by hyperglycaemia was markedly impaired in diabetic cirrhotic patients (glucagon levels at 35 min of 28 mmol/l glucose clamp: diabetics, 139 x/divided by 1.25 ng/l, non-diabetic cirrhotic patients, 24 x/divided by 1.20, controls, 21 x/divided by 1.15, p<0.001). Suppression of arginine-stimulated glucagon secretion by glucose was also impaired in diabetic cirrhotic patients, and to a lesser extent in non-diabetic cirrhotic patients.. Insulin secretory abnormalities in diabetic and non-diabetic cirrhotic patients are due to changes in maximal secretory capacity rather than altered B-cell sensitivity to glucose. The exaggerated glucagon response to arginine in alcoholic cirrhotic patients is not abolished by hyperglycaemia/hyperinsulinaemia. In diabetic alcoholic cirrhotic patients, the inhibitory effect of glucose on basal glucagon secretion is also markedly impaired.

Topics: Adult; Aged; Arginine; Basal Metabolism; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Glucagon; Glucose; Humans; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Liver Cirrhosis, Alcoholic; Middle Aged; Secretory Rate

To evaluate the frequency of autoimmune markers (islet cell antibodies (ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in newly diagnosed people with diabetes aged 40-75 years.. Two hundred fifty-nine consecutive patients (aged 40-75 years) with newly suspected diabetes diagnosed during a 2-year period were studied. The diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender, BMI, HbA1c, fasting C-peptide, ICA, and GADA were evaluated. The frequency of obesity was estimated using two different sets of criteria: 1) National Diabetes Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference population.. The annual incidence of diabetes was 106 per 100,000 people. The incidence of diabetes in those patients who were 40-54 years old was significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+; 10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203 diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in NIDDM was high but varied with its definition; the frequency of obesity was highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of 109 [41%] for men).. A striking male preponderance was found among incident cases of diabetes in people aged 40-54 years. Autoimmune markers were detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a conservative estimation, as many as 10 of 100,000 middle-aged and elderly subjects developed IDDM. The frequency of obesity in NIDDM was high but this was also the case in the reference population.

Topics: Adult; Aged; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Islets of Langerhans; Male; Middle Aged; Obesity; Sex Factors; Sweden

Mitochondrial tRNA(Leu)(UUR) gene mutation is one of the candidates in the pathogenesis of NIDDM. Especially the 3243 (A-->G) mutation is associated with the maternally-inherited diabetes and deafness. To evaluate the prevalence and characteristics of the 3243 point mutation in Koreans, we screened 433 Korean diabetic patients (220 men and 213 women). Genomic DNA was extracted from peripheral white blood cells and PCR was carried out with mitochondrial DNA primers (3130-3149, 3558-3539) encompassing the 3243 position. After digestion with Apa-1, five subjects showed polymorphism suggesting 3243 point mutation but when we directly sequenced the amplified DNA with an automatic sequencer, only 2 of the 5 patients were shown to have 3243 (A-->G) mutation and the other 3 subjects had 3426 (A-->G) mutation rather than 3243 mutation. Two diabetic patients with 3243 mutation were lean (BMI = 14.4, 17.0 kg/m2), had relatively lower fasting C-peptide concentrations (0.9 ng/ml each), and required insulin for management. In contrast, those with 3426 point mutation were not lean (BMI = 22.6-28.0 kg/m2), had relatively higher C-peptide levels (3.9-5.4 ng/ml), and could be managed with oral hypoglycemic agents. None of the 5 patients had deafness. In conclusion, the prevalence of 3243 point mutation in Korean diabetic patients was approximately 0.5% and we found a new mutation mimicking 3243 mutation by PCR-RFLP (restriction fragment length polymorphism) pattern. We suggest that sequencing of the PCR product or designing smaller PCR fragment size to enhance the specificity may help to identify the exact location of the point mutation.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; DNA, Mitochondrial; Female; Humans; Korea; Male; Middle Aged; NADH Dehydrogenase; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

Pancreas transplants are rarely done in type 2 (noninsulin dependent) diabetic patients. Most researchers believe that in type 2 diabetic patients, peripheral insulin resistance plays a central role and also is associated with relative insulin deficiency or an insulin secretory defect. This suggests that in patients receiving transplants, the new beta cells will be overstimulated, leading to beta cell "exhaustion" and graft failure.. Early in our experience, simultaneous pancreas-kidney transplant candidates were selected using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes and rapid onset of insulin use. Pretransplant sera were available for C-peptide analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African American (AA).. Thirteen patients (12 AA) with a nonfasting C-peptide level >1.37 ng/ml were identified. In these patients with high C-peptide levels, pancreas and kidney survival rates were 10O%. The results did not differ statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no differences between patient and pancreas-kidney survival rates when the patients were separated into AA and non-AA groups. The follow-up was 1-89 months, with a mean of 45.5 months.. Long-term pancreas graft function is attainable and beta cell "exhaustion" does not occur in patients with high preoperative C-peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term patient, kidney, and pancreas-kidney graft survival rates.

Topics: Adult; Black People; C-Peptide; Diabetes Mellitus; Female; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Survival Analysis; Time Factors

The objective of this work was to classify and describe the different types of diabetic patients detected in West Africa. In four health centres (three in Ivory Coast, one in Niger) 310 new cases were detected and followed up over 1 year. Classification was based on age at diagnosis, BMI, ketonuria, basal and stimulated C-peptide levels at inclusion, and response to antidiabetic therapy. In this population, males were predominant (sex ratio = 2.40), and random blood glucose levels very high at screening (mean +/- SE, 18.6 +/- 0.4 mmol/l). Only one case of fibrocalculous pancreatic diabetes and one possible case of diabetes mellitus related to malnutrition were detected. IDDM was diagnosed in 11.3% of the patients, half of them above 35 years. Leanness was observed in 59% of the patients with NIDDM. A dramatic decrease of fasting blood glucose was observed in all groups after 2 months of treatment, especially in NIDDM. As IDDM and non-obese NIDDM presented great similarities before treatment, even for C-peptide levels, a point score system is proposed to classify these two groups at baseline. In conclusion, it is confirmed that the form of diabetes previously defined as related to malnutrition is a very rare entity in black African populations. In contrast, African diabetes is characterised by the high proportion of NIDDM patients with low BMI, and reduced beta-cell function, rarely associated to ketonuria. This form of diabetes seems to be adequately controlled with oral hypoglycaemic drugs and/or diet in the year following diagnosis.

Topics: Adult; Africa, Western; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Ketone Bodies; Male; Middle Aged; Sex Factors

Topics: Age Factors; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Reference Values; Sex Characteristics; Tumor Necrosis Factor-alpha

To assess the prevalence of markers of autoimmune destruction of pancreatic beta-cells in patients with non-insulin dependent diabetes mellitus (NIDDM).. 127 hospitalized NIDDM patients subdivided to the following subgroups: non-obese with C-peptide < 0.3 nmol/l (NIDDM-(-)), non-obese with C-peptide > 0.3 nmol/l (NIDDM-(+)), obese with C-peptide < 0.3 nmol/l (NIDDM+(-)) and obese with C-peptide > 0.3 nmol/l (NIDDM2+). METHODS AND MEASURED PARAMETERS: Age, BMI, C-peptide, autoantibodies to glutamic acid decarboxylase (antiGAD-Ab), autoantibodies to islet cells (ICA), markers of specific cellular immunity CD4, CD8, CD19, CD4/CD8, CD4/CD45/RA+, CD4/CD45/RA-, NK (CD16+56), CD3/HLADR, organ specific/non-specific autoantibodies.. AntiGAD-Ab were positive in 5/15 (33.3%) NIDDM-(-), 1/32 (3.1%) NIDDM-(+), 2/9 (22.2%) NIDDM+(-) and in 3/71 (4.2%) NIDDM2+. The positivity of antiGAD-Ab in NIDDM-(-) and NIDDM+(-) was significantly higher (p < 0.05) than in NIDDM-(+) and NIDDM2+.. Some patients with manifestation of diabetes in older age initially classified and treated as having NIDDM may have in fact slowly evolving autoimmune insulin-dependent diabetes mellitus (LADA). These patients can be identified by measurement of antiGAD-Ab or other markers (ICA, IA-2) of autoimmune destruction of pancreatic beta-cells (AID). Moreover, in some patients both AID and insulin resistance may coexist in parallel.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Islets of Langerhans; Male; Middle Aged; Obesity

The main purpose of this work was to study the possible differences in insulin secretion in a large group of type 2 diabetic patients in relation to diabetes duration, obesity, and the presence of secondary failure after treatment with oral hypoglycemic agents.. There were 147 nonobese and 215 obese type 2 diabetic subjects, aged 35-80 years, investigated in a cross-sectional descriptive study Subjects were grouped according to whether glycemic control was good (mean blood glucose <8.5 mmol/l) or poor. Beta-cell function was assessed by measuring meal-stimulated insulin and C-peptide concentrations, as the mean of the three postprandial increments above the premeal value.. Basal C-peptide concentrations were significantly higher in obese than nonobese patients of both groups. The mean of meal-stimulated C-peptide concentrations was also significantly higher in obese than nonobese patients with good glycemic control, but not in the secondary failure groups. In nonobese and obese patients considered separately, a significant negative correlation between the mean of daily blood glucose and meal-stimulated C-peptide was observed (r=-0.705 and r=-0.679, respectively, P < 0.001) and the residual beta-cell function was significantly correlated with the known duration of diabetes and metabolic control, but not with BMI, in both groups.. On average, obese diabetic subjects showed higher meal-stimulated C-peptide than nonobese subjects only in well-controlled groups. In both obese and nonobese patients, an inverse association between meal-stimulated insulin secretion and duration of diabetes was observed. In obese patients, as in nonobese patients, the lower beta-cell function seems likely to be the major pathogenetic factor in the appearance of secondary failure, while being overweight plays only a minor role, thus showing that type 2 diabetes is the same disease in obese and nonobese patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Obesity; Postprandial Period

Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to Fanconi syndrome and end-stage renal failure. After renal transplantation, no recurrence of the disease occurs in the graft, but other organ involvement becomes evident later in life. Diabetes mellitus has been associated with cystinosis, but the mechanisms of impaired glucose tolerance have not yet been characterized. Here, we studied glucose tolerance, glucose constant decay (k-values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in eight patients with infantile cystinosis (three with impaired GFR (CRF) and five after kidney transplantation (KTX)). For comparison, 15 age-matched children with CRF and 15 age-matched KTX patients were analysed. Both early and second insulin secretion phases were diminished in patients with infantile cystinosis, whereas in CRF, k-values were no different from control patients. After renal transplantation, k-values were significantly lower in cystinotic patients with a markedly reduced early insulin secretion phase. There was a significant negative correlation between k-values and age in patients with cystinosis. Repetitive IVGTTs in these patients demonstrated progressive but rather slow loss of first phase insulin secretion and C-peptide production, suggesting a slowly reducing secretion potential of the beta cell due to cystine storage.. Unlike type I diabetes mellitus, glucose intolerance in patients with infantile cystinosis is characterized by a slow, progressive loss of insulin secretion and C-peptide production. For these patients, the data indicate a 50% risk of developing glucose intolerance by the age of 18 years. We recommend to perform intravenous glucose tolerance tests at 5-year intervals.

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Cystinosis; Diabetes Mellitus; Female; Glucose Intolerance; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Male

The glucoregulatory and hormonal responses to moderate-intensity exercise (50% VO2max for 45 min) were examined in subjects with type 2 diabetes and mild hyperglycemia. We studied seven obese subjects with type 2 diabetes and seven lean and seven obese control subjects (fasting plasma glucose levels, 7.5 +/- 0.5, 4.8 +/- 0.1, and 5.2 +/- 0.1 mmol/l, respectively). Glucose production, utilization, and cycling (flux between glucose and glucose-6-phosphate [G-6-P]) were measured with [6-(3)H]glucose and [2-(3)H]glucose using the constant specific-activity method. Insulin levels decreased normally during exercise in diabetic subjects. Plasma glucose levels decreased in diabetic subjects, but remained constant in control subjects. Basal glucose production was not different among groups and increased similarly during exercise. The decrease in plasma glucose in diabetic subjects was due to greater glucose utilization (867 +/- 83 vs. 726 +/- 143 micromol x m(-2) x min(-1); P < 0.05). This was a consequence of the mass effect of hyperglycemia, since glucose metabolic clearance increased similarly in all groups. Glucose cycling, expressed as a percentage of total glucose output (i.e., flux through G-6-P) was elevated at rest (P < 0.01), but decreased during exercise (P < 0.01). The catecholamine response to exercise was blunted in diabetic subjects, presumably indicating autonomic dysfunction. In conclusion, during moderate-intensity exercise in obese diabetic subjects with mild hyperglycemia, 1) insulin secretory responses were normally regulated; 2) glucose homeostasis was different from that in nondiabetic subjects because glucose levels decreased during exercise; 3) the decrease in plasma glucose was due to greater-than-normal rates of glucose utilization, which were sustained by hyperglycemia; and 4) elevated basal rates of glucose cycling decreased during exercise, presumably because exercise simultaneously lowered plasma glucose, was associated with a blunted catecholamine response, and accentuated an underlying defect in hepatic glucokinase activity in type 2 diabetes.

Topics: Adult; Alanine; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Exercise; Female; Glucose; Glucose-6-Phosphate; Homeostasis; Humans; Hyperglycemia; Insulin; Lactic Acid; Male; Obesity; Oxidation-Reduction; Oxygen Consumption; Tritium

The aim of the present study was to establish whether the persistence of residual beta-cell activity after long-term diabetes mellitus (DM) exerts a protective role on luteinizing hormone (LH) secretion.. The LH responses to stimulation with gonadotropin-releasing hormone (Gn-RH) (100 microg in an i.v. bolus) or naloxone (4 mg injected in an i.v. bolus, followed by the constant infusion of 8 mg in 2 h) were measured in C-peptide-positive (CpP) and C-peptide-negative (CpN) normally menstruating women with short-term (group 1 < 3 years, CpP n = 11, CpN n = 11) or long-term (group 2 > 10 years, CpP n = 11, CpN n = 11) DM and in age-matched normal control subjects (n = 11).. Gn-RH induced significant increments in LH secretion in all groups. Significant LH responses to naloxone were observed in all groups, except in group 2 CpN patients. However, the LH response to either Gn-RH or naloxone was significantly lower in group 1 CpN, group 2 CpP and group 2 CpN patients than in the normal control subjects. Furthermore, the LH response was significantly lower in group 2 CpP than in group 1 CpP patients and in group 2 CpN than in group 1 CpN subjects.. These results indicate a role for both deficiency in residual endogenous insulin secretion and duration of diabetes in the derangement of LH secretory control. The data suggest that the protective role exerted by residual beta-cell activity on LH secretion during the early years of DM diminishes with time elapsed after the onset of diabetes mellitus.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Secretion; Luteinizing Hormone; Naloxone; Time Factors

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Deafness; Diabetes Complications; Diabetes Mellitus; DNA, Mitochondrial; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Japan; Middle Aged; Point Mutation; RNA, Transfer, Lys

The third form of maturity-onset diabetes of the young is caused by mutations in the hepatocyte nuclear factor-1alpha gene. Recently, we demonstrated an association between a prevalent polymorphism at codon 98, Ala/Val98, of this gene and a 20% decreased insulin release during an oral glucose tolerance test (OGTT) in middle-aged glucose-tolerant Danish Caucasian subjects. The major objective of the present study was to replicate this finding among glucose-tolerant first degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an OGTT with measurements of plasma glucose, serum insulin, and serum C peptide during the test. Thirty-three heterozygous carriers of the Ala/Val variant were identified, whereas no subjects had the variant in its homozygous form. Ala/Val carriers had a 20% reduction in serum C peptide at 30 min during the OGTT (1225+/-636 vs. 1507+/-624 pmol/L; P=0.02) compared to wild-type carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and Ala/Ala homozygotes. In conclusion, among Danish glucose-tolerant first degree relatives of type 2 diabetic patients the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene is associated with a decreased serum C-peptide secretion during an OGTT. This finding confirms our previously reported observation of the functional importance of the variant to insulin secretion during an OGTT among middle-aged healthy subjects.

Topics: Adult; Amino Acid Sequence; C-Peptide; Diabetes Mellitus; DNA-Binding Proteins; Female; Genetic Variation; Glucose; Glucose Tolerance Test; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Male; Middle Aged; Nuclear Proteins; Polymorphism, Genetic; Transcription Factors

The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.

Topics: Adipose Tissue; Aged; Biomarkers; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Male; Middle Aged; Obesity; Reference Values; Tumor Necrosis Factor-alpha

In obesity, a central pattern of fat distribution is mostly associated with hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the development of non-insulin-dependent diabetes mellitus and cardiovascular disease. In addition, in obesity, changes in energy expenditure are hypothesized to be involved in the development or maintenance of excessive body fat storage. In this study, abdominal fat distribution by computed tomographic (CT) scan was used to study the relation between the visceral fat depot, insulin secretion, and insulin sensitivity in a group of obese subjects with normal glucose tolerance (n = 26; body mass index [BMI], 39 +/- 1 kg/m2) and a group of normal-weight control subjects (n = 9; BMI, 23 +/- 1 kg/m2). The minimal model method was used to assess insulin sensitivity, S(I), and first-phase (phi1) and second-phase (phi2) beta-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body weight). Moreover, we evaluated the relationships between these parameters and the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured by indirect calorimetry. The data show the following: (1) in obese subjects, phi1 is greater but not statistically different from the value in control subjects (252 +/- 41 v 157 +/- 25 dimensionless 10(9)); (2) phi2 is significantly higher in obese subjects (27 +/- 4 v 14 +/- 2 min(-1) x 10(9), P < .05), with a positive correlation between the amount of visceral adipose tissue (VAT) and phi2 (r = .49, P < .05); (3) S(I) is decreased in the obese group (2.8 +/- 0.3 v 9.7 +/- 1.6 10(-4) x min(-1)/microU x mL(-1)), P < .0001), with a negative correlation of S(I) with the adiposity index BMI (r = -.67, P < .0001) and VAT (r = .56, P < .05); (4) RMR, expressed in absolute terms, was significantly increased in obese versus lean subjects (5.9 +/- 0.2 v 4.6 +/- 0.3 kJ/min, P < .01), whereas when RMR was adjusted for fat-free mass (FFM), the difference between the two groups disappeared (0.09 +/- 0.003 v 0.09 +/- 0.002 kJ/min x kg FFM). We did not observe any difference in GIT between lean and obese subjects. Moreover, GIT was significantly correlated with FFM (r = .69, P < .005), but not with BMI. The amount of VAT did not correlate with RMR or GIT. In conclusion, these results suggest that in obese subjects with normal glucose tolerance, insulin sensitivity is impaired and the beta-cell hyperresp

Topics: Abdomen; Adipose Tissue; Adult; Body Composition; C-Peptide; Diabetes Mellitus; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Obesity; Sensitivity and Specificity

To determine insulin action and insulin secretory function in patients with hemochromatosis, and to find evidence for or against hypothesized pathogenetic mechanisms for the abnormal glucose metabolism associated with hemochromatosis. These mechanisms include decreased beta-cell secretion of insulin due to iron overload, insulin resistance and genetic factors.. Prospective in vivo study.. Seventeen subjects with hemochromatosis, of whom 4 had cirrhosis but not diabetes mellitus, 6 had diabetes mellitus and 7 had neither; 10 controls.. Insulin sensitivity and insulin secretion were determined during an intravenous glucose tolerance test. Insulin secretion was measured as the acute insulin response to glucose (AIRg). Insulin sensitivity (Si) was quantified with the minimal-model method. Of the patients with hemochromatosis, 14 agreed to undergo a second metabolic study after treatment with venous phlebotomy.. All subjects with hereditary hemochromatosis had impaired glucose tolerance as measured by K(g) (rate of glucose disappearance). Subjects who were free of both diabetes mellitus and liver cirrhosis had a normal S1 and a decreased AIRg. In these subjects, phlebotomy treatment normalized serum ferritin levels, increased AIRg by 35% and normalized glucose tolerance (K(g)). Subjects with hemochromatosis and cirrhosis had a reduced Si and maintained a normal insulin secretion. Phlebotomy treatment did not change these parameters. Subjects with hemochromatosis and diabetes mellitus had both a reduced Si and AIRg, and these parameters were unaffected by phlebotomy treatment.. These results suggest that iron overload can impair insulin secretion and glucose tolerance early in hereditary hemochromatosis, before cirrhosis occurs. Phlebotomy treatment can reverse these defects. Impaired glucose tolerance resulting from insulin resistance in subjects with cirrhosis or diabetes mellitus is not affected by phlebotomy treatment.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Ferritins; Glucose Tolerance Test; Glycated Hemoglobin; Hemochromatosis; Humans; Insulin; Insulin Secretion; Iron; Liver; Liver Cirrhosis; Middle Aged; Phlebotomy; Prospective Studies

To determine the prevalence of past and current obesity among patients with non-insulin-dependent diabetes mellitus (NIDDM) and to define the clinical characteristics of non-obese NIDDM patients in South Korea, we studied a cross-section of 749 NIDDM patients and a group of age- and sex-matched control subjects. Current height, weight and waist-to-hip ratio (WHR), the history of weight changes and the family history of diabetes were recorded. Obesity was defined as body mass index (BMI) > 25 kg/m2. The maximum lifetime BMI of diabetic patients was significantly higher than that of control subjects (P < 0.001). Compared with control subjects, current BMI was higher in diabetic women (P < 0.001) but not in diabetic men. In contrast, WHR of both diabetic men and women were significantly higher than those of controls (P < 0.05). BMI and WHR correlated significantly with fasting C-peptide levels and log-triglyceride levels in NIDDM patients. As a whole, 72% of the South Korean NIDDM patients had a history of past obesity as assessed by their maximum weight, while only 38% of them were currently obese. Compared with obese patients, non-obese patients were characterized by lower fasting serum C-peptide levels (P < 0.001), a higher percentage of insulin treatment (P < 0.05), lower maximum BMI (P < 0.001) and more pronounced weight loss from the time at their maximum weight (P < 0.001). In summary, increased upper body adiposity and a history of past obesity were associated with NIDDM in South Korea. Although most South Korean NIDDM patients were previously obese, many of them were currently not obese. Lower maximum BMI, lower serum C-peptide levels and a higher percentage of insulin treatment in non-obese NIDDM patients suggest that the capacity to increase insulin secretion in response to increasing weight gain is rather limited in these patients.

Topics: Adipose Tissue; Adult; Aged; Blood Pressure; Body Constitution; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Korea; Male; Middle Aged; Multivariate Analysis; Obesity; Sex Factors; Time Factors

To evaluate both the concordance in the classification of diabetes by clinical and C-peptide criteria and, prospectively, the consistency of the classification by C-peptide.. Individuals with diabetes who were enlisted in the prospective epidemiological study of diabetic neuropathy (Rochester Diabetic Neuropathy Study [RDNS]) were classified clinically by National Diabetes Data Group (NDDG) criteria to IDDM and NIDDM at entry to the study. In addition, C-peptide response to 1 mg glucagon was measured at entry for the classification to IDDM (basal C-peptide, < 0.17 pmol/ml; increment above basal, < 0.07 pmol/ml) and NIDDM (all other responses) and for concordance with the clinical classification made. The consistency of the C-peptide response was assessed every 2 years for up to 8 years.. Among 346 individuals with diabetes, 84 were classified as IDDM and 262 as NIDDM by clinical algorithm. COncordance with the C-peptide response occurred in 89% of the patients and remained consistent during 8 years of follow-up. Among the 37 patients with discordant clinical and C-peptide classification, those considered clinically to have NIDDM had a consistent IDDM C-peptide response during follow-up, and most of those considered to have IDDM clinically eventually showed an IDDM C-peptide response during follow-up.. Clinical criteria for the classification of diabetes are highly correlated with the assessment of insulin secretory reserve. A small number of individuals considered to have NIDDM clinically or by C-peptide have or develop an IDDM peptide response.

Topics: Adolescent; Adult; Age of Onset; Algorithms; Biomarkers; C-Peptide; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus; Female; Follow-Up Studies; Glucagon; Humans; Injections, Intravenous; Male; Middle Aged; Prospective Studies

Topics: Adolescent; C-Peptide; Diabetes Mellitus; Female; Humans; Immunosuppressive Agents; Insulin Resistance; Kidney Transplantation; Tacrolimus

Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin action in vitro and in intact mammals, but it is not known which mediator is involved in insulin action under physiological conditions, nor is it known whether insulin resistance alters the mediator profile under such conditions. We therefore investigated the effects of glucose ingestion on changes in the bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of mediators were partially purified from serum before and after glucose ingestion. The first was eluted from an anion exchange resin with HCl pH 2.0, and bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH 1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0 IPG increased to approximately 120% of the pre-glucose ingestion value at 60-240 min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in either IPG after glucose ingestion in the insulin-resistant group. These data suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect on peripheral glucose utilization in man under physiological conditions. The data further show, for the first time, a defective change in the bioactivity of an insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia, suggesting that inadequate generation/release of IPGs is associated with insulin resistance.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Glucose; Humans; Inositol Phosphates; Insulin; Insulin Antagonists; Insulin Resistance; Kinetics; Male; Middle Aged; Myocardium; Obesity; Polysaccharides; Pyruvate Dehydrogenase Complex; Reference Values; Swine; Time Factors

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Recombinant Proteins

A case with diabetes mellitus associated with growth hormone (GH)-producing pituitary adenoma is described. A 56-year-old woman who had been treated for diabetes mellitus for 3 years, was admitted for the treatment of hyperglycemia. She showed a few acromegalic features and her plasma GH level was 146 +/- 16 ng/ml. After improvement of plasma glucose level by insulin injection, octreotide therapy (100 micrograms/8 hours) was started. Seven days after the initiation of octreotide therapy, the fasting plasma glucose level was almost normalized without insulin injection. After the octreotide treatment, urinary C-peptide excretion was significantly decreased and the plasma GH level became within normal range. In this case, octreotide appears to have improved the insulin sensitivity by reducing the plasma GH level.

Topics: Acromegaly; Adenoma; Antineoplastic Agents, Hormonal; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Intolerance; Human Growth Hormone; Humans; Hyperglycemia; Insulin Resistance; Middle Aged; Octreotide; Pituitary Neoplasms

Topics: Adult; Alkaline Phosphatase; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Intestines; Isoenzymes; Obesity

Pheochromocytoma usually is associated with a combination of various manifestations caused by overproduction of catecholamines. We encountered a case of an occult, catecholamine-secreting pheochromocytoma. A 70-year-old man was admitted to the hospital because of anorexia. He had been treated for diabetes mellitus for 4 years; during this period he did not have any other symptoms related to pheochromocytoma. At admission, serum epinephrine, norepinephrine, and glucose levels and urinary excretion of total metanephrine were elevated. A tumor was detected in the left adrenal region and diagnosed as pheochromocytoma. After tumor resection, the increased levels of catecholamines and glucose and the decreased urinary C-peptide were normalized. This suggests that the pheochromocytoma caused hyperglycemia without other manifestations for a long time.

Topics: Aged; Blood Glucose; C-Peptide; Catecholamines; Diabetes Mellitus; Diagnostic Errors; Humans; Hyperglycemia; Insulin; Male; Pheochromocytoma; Tomography, X-Ray Computed

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Topics: Aged; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Erythropoietin; Ferritins; Hemochromatosis; Humans; Iron; Iron Overload; Islets of Langerhans; Male; Phlebotomy; Recombinant Proteins

The majority (> 80%) of patients with non insulin dependent diabetes mellitus (NIDDM) present in Europe and America are obese. In developing countries like India, most NIDDM (> 60%) are non-obese and many are actually lean with a body mass index (BMI) of < 18.5 and are referred to as 'lean NIDDM'. This paper compares the clinical profile of a cohort of 347 lean NIDDM, with a group of 6274 NIDDM of ideal body weight (IBW) and 3252 obese NIDDM attending a diabetes centre at Madras in South India. The lean NIDDM who constituted 3.5% of all NIDDM patients seen at our centre, had more severe diabetes and an increased prevalence of retinopathy (both background and proliferative), nephropathy and neuropathy. Although a larger percentage of the lean NIDDM patients were treated with insulin, 47% of the males and 53% of the females were still on oral hypoglycaemic agents even after a mean duration of diabetes of 9.2 +/- 8.1 years. Studies of GAD antibodies, islet cell antibodies (ICA) and fasting and stimulated C-peptide estimations done in a small subgroup of the lean NIDDM showed that they were distinct from IDDM patients. More studies are needed on metabolic, hormonal and immunological profile of lean NIDDM seen in developing countries like India.

Topics: Adult; Autoantibodies; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diastole; Dose-Response Relationship, Drug; Fasting; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; India; Insulin; Islets of Langerhans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Obesity; Postprandial Period; Smoking; Systole; Triglycerides

When diabetes has been diagnosed, its classification into different types is traditionally carried out according to clinical criteria. But with arising of new parameters, one of which is C-peptide, and various subtypes of diabetes, it became more difficult. So, in order to improve the accuracy of the classification, 270 diabetic patients and 269 controls, all black senegalese subjects, were submitted to a two-step oral glucose tolerance test (0 and 120 min.) with determination of plasma glucose and C-peptide concentrations. The majority of NIDDM were confirmed at the opposite of IDDM; furthermore, it has been pointed out a group corresponding with impaired glucose tolerance (IGT) among the initial controls. When comparing the two classification modes, before and after plasma C-peptide determination, it appeared statistically significant differences with p values of 10(-4) for both IDDM and NIDDM.

Topics: Adult; Black People; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Senegal

High insulin levels are a recognized risk factor for atherosclerosis. Microvascular endothelium is more susceptible to metabolic and mitogenic effects of insulin than large-vessel endothelium. Besides their atherogenic effect, high insulin levels impair fibrinolysis by enhancing plasminogen activator inhibitor-1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology.. One hundred ninety-four consecutive patients presenting with symptomatic cerebrovascular disease were assigned to three subgroups that were differentiated by clinical presentations, brain imaging studies, and extracranial as well as transcranial vascular ultrasound findings: (1) patients with lacunes (n = 20), (2) patients with subcortical arteriosclerotic encephalopathy (n = 35), and (3) patients with strokes due to large-vessel disease (n = 99). Patients who had suffered a cryptogenic (n = 9) or cardioembolic (n = 16) stroke or who showed characteristics of the microangiopathy and macroangiopathy groups (n = 15) were not further evaluated. Thirty patients without manifestations of cerebrovascular disease were also examined. Fasting blood glucose, insulin, and C-peptide levels were determined in all subjects.. There were no significant differences in age or sex among the three groups and control patients. Insulin levels were significantly higher in the lacunar group compared with the subcortical arteriosclerotic encephalopathy group, the macroangiopathy group, and the control patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney test). There was a statistically significant difference in insulin concentrations between the microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes) and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney). The same was true for the distribution of C-peptide levels and to a minor extent blood glucose values, but these differences failed to reach statistical significance.. Elevated insulin levels potentially represent a pathogenetic factor in the development of cerebral small-vessel disease, predominantly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether changes in hemorheology are operative as well remains to be evaluated.

Topics: Aged; Arteriosclerosis; Blood Glucose; C-Peptide; Cerebrovascular Circulation; Cerebrovascular Disorders; Diabetes Mellitus; Female; Humans; Hyperinsulinism; Hypertension; Insulin; Male; Microcirculation; Middle Aged; Prevalence; Risk Factors

Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Chest Pain; Coronary Disease; Diabetes Mellitus; Ethnicity; Female; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Odds Ratio; Proinsulin; Reference Values; Regression Analysis; Risk Factors; Sex Factors; Smoking

Increased resting energy expenditure (REE) and a blunted thermic effect of glucose (TEF) have been reported in obese subjects with non-insulin-dependent diabetes mellitus (NIDDM). I questioned whether the abnormal REE and TEF would be corrected by normalizing glycemia with insulin or a very-low-energy diet (VLED). Three male and four female obese subjects with NIDDM [weighing 108 +/- 6 kg and with body mass index (in kg/m2) of 39 +/- 2] received a weight-maintaing formula diet containing 95 g protein/d for 15 d then a 1.7-MJ, 93-g-protein VLED for 27 d. Insulin was given from days 1 to 8 in doses sufficient to normalize glycemia. REE was measured weekly and TEF was measured on days 8 and 15 of isoenergetic feeding and 28 d after the VLED by using a ventilated-hood indirect calorimeter. Weight decreased 9.8 +/- 1 kg during the VLED. REE was 3% lower with insulin treatment than during hyperglycemia (7878 +/- 364 compared with 8125 +/- 381 kJ/d, P = 0.002). REE decreased by 20% to 6494 +/- 280 kJ/d by week 4 of the VLED. After 112 g oral glucose, increments in energy expenditure were significantly greater during isoenergetic feeding with insulin than without (7.5 +/- 1.3% compared with 4.3 +/- 0.9% above REE) and after the VLED (10.5 +/- 1.0% above REE, P < 0.05). Plasma glucose excursions were greatest without exogenous insulin (peak 21.5 +/- 1.8 mmol/L at 120 min, 16.3 +/- 1.9 mmol/L at 225 min). Plasma fatty acid excursions were the lowest with insulin treatment. The integrated plasma glucose and fatty acid responses above baseline did not differ among studies; the integrated insulin and C-peptide responses were greater after the VLED. Cumulative nonoxidative glucose disposal (stored glucose) was higher with insulin therapy than without (52 +/- 6 compared with 35 +/- 7 g/210 min, P < 0.05) and increased significantly to 66 +/- 6 g after the VLED (compared with the isoenergetic diet without insulin). TEF correlated significantly with integrated C-peptide and insulin responses. The percentage increase in TEF with euglycemia (with insulin and VLED) correlated with the percentage increase in stored glucose (P < 0.05). The greater TEF was associated with a greater insulin response, which was probably responsible for the greater stored glucose.

Topics: Adult; Basal Metabolism; Blood Glucose; Body Temperature Regulation; C-Peptide; Calorimetry, Indirect; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Intake; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Kinetics; Male; Middle Aged; Obesity

The purpose of the present study was to characterize secondary failure (SF) to oral hypoglycaemic agents by assessment of threshold insulin-secretion values in relation to diabetes duration. One hundred and forty-seven nonobese diabetic patients, 35 to 80 years of age, with disease duration ranging from 1 to 36 years, were studied. Beta-cell function was assessed by meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations. The quality of glycaemic control was considered good if mean daily blood glucose was less than 8.5 mmol/l. One group with good (NOb-GC) and another with poor control (NOb-SF) were established. Mean daily glycaemia was negatively correlated with delta CP or delta aCP (r = -0.703 vs r = -0.696; p < 0.001) more than with basal C-peptide (r = -0.453; p < 0.001). A close positive correlation between meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations was observed (r = 0.869; p < 0.001). Residual beta-cell function (delta CP and delta aCP) was significantly correlated with known disease duration in both groups (GC: r = -0.693 and SF: r = -0.680; p < 0.001). Nonobese patients with SF showed early impaired secretion during the first years of disease, meal-stimulated delta CP being below 0.350 mmol/l. The most useful result in this study was the incremental value of C-peptide (delta CP), which showed minimal overlapping between the two groups. Basal, postprandial or postglucagon absolute values were less discriminating. The daily profile allowed measurement of both glycaemic control and insulin production after a regular meal. The validity of this measurement was confirmed by the strong correlation between meal-stimulated and glucagon-stimulated delta C-peptide concentrations. This parameter is a useful physiological marker of secondary failure.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Progression; Female; Food; Glucagon; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Linear Models; Male; Middle Aged; Obesity; Stimulation, Chemical; Treatment Outcome

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Coma; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Insulin; Japan; Male; Obesity

To test the hypothesis that hyperinsulinemia and glucose intolerance are present at an early age in australian aborigines and can be used to predict the eventual development of NIDDM.. Baseline anthropometric, pubertal stage, and blood pressure data were collected for 100 Australian aboriginal children and adolescents in 1989. Plasma concentrations of glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol were measured before and during an oral glucose tolerance test. All measurements were repeated in 74 individuals from the original study population in 1994. Results were compared among hyperinsulinemic and normoinsulinemic subjects, and subjects with normal or abnormal glucose tolerance.. The percentage of subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol concentrations in plasma. Dyslipidemia was particularly prevalent among male subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in 1994, four were classified as hyperinsulinemic in 1989 and four were not.. The major finding of this study is the high prevalence of risk factors for NIDDM and cardiovascular disease in this population of aboriginal children and adolescents. Abnormalities of carbohydrate and lipid metabolism were well established by late in the second decade of life. Although many subjects had high insulin levels and there was evidence of insulin resistance in the population, hyperinsulinemia did not predict the development of abnormal glucose tolerance 5 years later.

Topics: Adolescent; Anthropometry; Australia; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Hyperlipidemias; Insulin; Male; Native Hawaiian or Other Pacific Islander; Obesity; Risk Factors; Sex Characteristics; Sex Factors; Time Factors; Triglycerides

Derangements in the GH/IGF axis are common in patients with diabetes mellitus. In insulin-dependent diabetes mellitus (IDDM), these disturbances seem to be due to a partial defect in GH action on its own receptor or via a post-receptor defect. In non-insulin-dependent diabetes mellitus (NIDDM), data are limited, and the regulation of the GH receptor (GHR) remains unclear. However, animal studies with diabetic rats demonstrated that the GHR density may be influenced by insulin disposal at the hepatocyte. With respect to this hypothesis we studied the relation between peripheral insulin status and the serum GH-binding protein (GHBP), which reflects indirectly the GHR density in the tissues. Patients with IDDM were compared to a NIDDM group as well as to a group of healthy subjects.. Basal blood samples for the determination of serum GHBP, GH, and IGF-I were obtained from patients with IDDM (n = 27), subjects with NIDDM (n = 112) and healthy controle (n = 42). Insulin, proinsulin, C-peptide and IGF-binding protein 1 (IGFBP-1) serum levels were used to estimate the insulin status in diabetic patients.. GHBP serum levels were significantly lower in patients with IDDM than in either NIDDM or controls (P < 0.001). Conversely, the IGF-I levels were reduced in both groups of diabetics. A subgroup of hypoinsulinaemic NIDDM patients showed significantly decreased GHBP concentrations (P < 0.05) compared to the NIDDM sub-group with hyperinsulinaemia. Furthermore, GHBP levels were significantly decreased in insulin-treated patients with NIDDM compared to either non-insulin-requiring subjects or normal controls (P < 0.05). A significant direct relation was found between levels of GHBP and total insulin dose (P < 0.01) in patients with IDDM. In the NIDDM group, GHBP was correlated with proinsulin (P < 0.001), C-peptide (P < 0.01), Insulin (P < 0.05) and inversely with IGFBP-1 (P < 0.001). Multiple linear regression analysis indicated a significant contribution of proinsulin and IGFBP-1 to the variation of GHBP.. Decreased GHBP levels in IDDM as well as in NIDDM correlate with insulinopenia. Since the degree of insulinopenia depends on the capability of the beta-cells to secrete proinsulin, C-peptide and insulin, we hypothesize that these hormones at least partially influence the serum level of GHBP. Low GHBP levels may reflect a reduced GH receptor density and a concomitant GH insensitivity, which leads to an impaired IGF generation in insulin-deficient patients.

Topics: Adult; Aged; C-Peptide; Carrier Proteins; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Male; Middle Aged; Proinsulin; Receptors, Somatotropin

To determine whether blood pressure is associated with 24-h urinary C-peptide excretion in subjects with varying degrees of glucose tolerance, we studied 247 Japanese men aged 30-69 who had never been treated with antihypertensive medications or with insulin. Plasma glucose and insulin responses during a 75-g oral glucose tolerance test, blood pressure and body mass index were obtained and urinary C-peptide excretion, in total and per kg body weight, were examined by 24-h urine collection. In monovariate analyses, urinary C-peptide excretion per kg body weight increased significantly as the blood pressure level rose (p < 0.05). After adjustment for age and body mass index by analysis of covariance, this relationship remained significant (p < 0.05), where adjusted mean values (+/- SEM) of urinary C-peptide per kg body weight were 1.56 +/- 0.05 microgram/24h/kg in the normotensive group and 2.04 +/- 0.17 microgram/24h/kg in the hypertensive (stage 2-4) group. When stratified simultaneously by glucose tolerance status and blood pressure level, adjusted mean values of urinary C-peptide per kg body weight were significantly higher in diabetic hypertensives than in diabetic normotensives. These results suggest that increase in 24-h urinary C-peptide excretion, i.e. 24-h insulin secretion, might contribute to an elevation of blood pressure both in normal and diabetic individuals.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged

Topics: Autoantibodies; C-Peptide; Case-Control Studies; Child; Diabetes Complications; Diabetes Mellitus; Glucose Intolerance; Humans; Oman; Vitiligo

Disproportionate hyperproinsulinaemia is a manifestation of the beta-cell dysfunction observed in NIDDM. However, it is unclear when this abnormality develops and whether it predicts the development of the disease. To examine whether changes in proinsulin levels predict the development of NIDDM, baseline measurements of proinsulin and immunoreactive insulin levels were made in 87 second-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM. Subjects were categorized at baseline using WHO criteria as having normal glucose tolerance (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a 5-year follow-up period, subjects were recategorized as having NGT, IGT or NIDDM using the same criteria. During follow-up, 16 subjects developed NIDDM while 71 were NGT or IGT. At baseline, individuals who subsequently developed NIDDM were more obese as measured by intra-abdominal fat area on computed tomography (p = 0.046), had higher fasting glucose (p = 0.0042), 2-h glucose (p = 0.0002), fasting C-peptide (p = 0.0011), fasting proinsulin levels (p = 0.0033), and had disproportionate hyperproinsulinaemia (p = 0.056) when compared to those who remained NGT or IGT after 5 years of follow-up. These findings suggest that alterations in proinsulin levels may also predict the subsequent development of NIDDM.

Topics: Asian; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Japan; Male; Middle Aged; Obesity; Predictive Value of Tests; Proinsulin; Reference Values; Washington

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbA1c, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2-32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P < 0.05) and had higher HbA1c and sCD8 serum levels (P < 0.0001), respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P < 0.005 and P < 0.0001, respectively), and lower C-peptide concentrations (P < 0.005 and P < 0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (> 737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (< 0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (> 20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.

Topics: Adolescent; Adult; Antigens, CD; Autoantibodies; Biomarkers; Body Mass Index; C-Peptide; CD8 Antigens; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Histocompatibility Testing; HLA-DR3 Antigen; Humans; Insulin; Islets of Langerhans; Male; Predictive Value of Tests; Prospective Studies

% of type I diabetics are not administering insulin according to the intensified conventional therapy schedules, only 16.8% of all type II diabetics are treated with diet only. Type II diabetics are much too often treated with pre-mixed insulins of too high dosage (26.2%) or with oral hypoglycemics (46.2%) of which 90% were sulphonylureas and nearly exclusively glibenclamide. Oral hypoglycemics with extrapancreatic activity or combined therapies were not common among the patients.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Complications; Diabetes Mellitus; Employment; Female; Germany; Glycated Hemoglobin; Government Agencies; Humans; Hypoglycemic Agents; Inpatients; Insurance, Health; Lipids; Male; Middle Aged; Serum Albumin

Topics: Adult; Age of Onset; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin; Male; Obesity

Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes).. We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis.. Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied.. The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Topics: Adult; Aged; Amylases; Bicarbonates; C-Peptide; Chronic Disease; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreas; Pancreatitis

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Male; Middle Aged; Obesity

The University of California Islet Transplant Consortium was formed to evaluate the feasibility of performing clinical islet transplantation at different transplant centers by using a single centralized islet isolation laboratory.. From July 1992 through February 1995 seven adult islet transplantations were performed, six allografts and one autograft. Once procured, human pancreata were brought to the UCLA-VA Islet Core Laboratory for islet isolation and purification, which were then transported to different centers for transplantation. Patients 1 through 3 received their transplants in Los Angeles, patient 4 received her islet transplant in Torrance, and patients 5 through 7 received their transplants in San Francisco.. Although none of these patients achieved insulin independence, four of seven had functioning grafts longer than 6 months as indicated by circulating C-peptide level greater than 0.7 ng/ml. Furthermore, improved glucose control as shown by a decreased insulin requirement was seen in 57% (four of seven patients) of these patients. The ability to isolate islets at a single laboratory and transport them long distances to different centers was shown in patients 4 through 7.. Islet transplantation can be performed with improvements in blood glucose control, and islets can be isolated at a centralized location and successfully transported to different centers for transplantation.

Topics: Adult; Blood Glucose; C-Peptide; California; Child; Diabetes Mellitus; Female; Graft Survival; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Registries; Tissue Donors

In this article, the author discusses the prevalence of insulin autoantibodies (IAA) and endogenous insulin secretion in Saudi patients at the onset of diabetes. A positive result, defined as a value greater than 3 SD above the mean binding of normal, was found in 8 (7.6%) of 105 of the patients with diabetes and in 3 (5.7%) of 53 of the healthy control subjects. The relation between the presence of IAA and the pancreatic beta cell secretory activity was studied by determining the levels of insulin and C-peptide in the fasting state and 6 minutes after intravenous injection of 1 mg glucagon. All the IAA positive subjects had a response to glucagon stimulation test. A positive correlation was found between basal and after stimulation for both insulin and C-peptide (r = 0.79, P < 0.001; r = 0.85, P < 0.001 for insulin and r = 0.76, P < 0.001; r = 0.81, P < 0.001 for C-peptide, respectively). Therefore, the current finding indicates that there is no direct effect of IAA on the pancreatic beta cell potential activity in Saudi patients with diabetes at the time of diagnosis, suggesting further that these patients have no insulin deficiency or have mild insulin dependency.

Topics: Adult; Aged; Autoantibodies; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Middle Aged

To compare the pancreatic exocrine and beta-cell function in the two variants of malnutrition-related diabetes mellitus (MRDM): fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD).. Fecal chymotrypsin (FCT) and fasting C-peptide levels were measured in 20 consecutive patients with FCPD and 19 with PDPD. FCPD was diagnosed by pancreatic calcification on ultrasonography, while the diagnosis of PDPD was made on the basis of low body mass index, severe diabetes requiring insulin therapy, and ketosis resistance on interruption of insulin. Twenty patients with type I diabetes and 32 healthy subjects served as control subjects.. Both FCPD and PDPD patients had diminished levels of FCT when compared with those of control subjects and patients with type I diabetes. However, FCT levels were significantly lower in subjects with FCPD (median 0.4 U/g, range 0-8.9 U/g), in comparison with those with PDPD (4.7 U/g, 0.6-40.5 U/g; P < 0.001). Of the FCPD patients, 13 of 20 (65%) had severe exocrine pancreatic deficiency (FCT < 1 U/g) vs. 3 of 19 (15.8%) PDPD subjects (P < 0.01). In comparison with control subjects, fasting serum C-peptide levels were significantly diminished in both MRDM groups. However, C-peptide levels in subjects with FCPD (mean +/- SE, 0.22 +/- 0.04 nmol/l) and PDPD (0.26 +/- 0.04 nmol/l) were comparable.. Among the two variants of MRDM, subjects with FCPD have severe pancreatic exocrine deficiency in comparison with those with PDPD, even though their C-peptide levels are comparably diminished. This suggests that the pathogenesis of these two entities may differ or that the genetic and/or environmental factors leading to exocrine damage are different.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Chymotrypsin; Diabetes Mellitus; Diabetes Mellitus, Type 1; Feces; Female; Glycated Hemoglobin; Humans; India; Insulin; Insulin Secretion; Islets of Langerhans; Male; Nutrition Disorders; Pancreas; Pancreatic Diseases; Reference Values; Statistics, Nonparametric

The tissue sensitivity to insulin was evaluated using the hyperinsulinemic euglycemic clamp technique in a 44-year old male with Werner's syndrome associated with diabetes mellitus. In addition, the autophosphorylation of insulin receptors and the number of autophosphorylated insulin receptors were measured in his erythrocytes by a new enzyme-linked immunosorbent assay. He had an increased serum insulin level (30.5 microU/ml) in addition to hyperglycemia (226 mg/dl), suggesting that he had insulin-resistant diabetes mellitus. A clamp study revealed that his insulin-stimulated glucose disposal rate (2.80 mg/kg/min) was comparable to that in noninsulin-dependent diabetes mellitus (4.14 +/- 1.94 (SD) mg/kg/min, n = 23). The number of autophosphorylated insulin receptors per 300 microliters of erythrocytes was also identical to that in normal control subjects. In addition, the autophosphorylation of insulin receptors determined at six different insulin concentrations was within the normal range, even when it was expressed as per 300 microliters of erythrocytes as well as per unit receptor. These results demonstrate that insulin resistance in the patient with Werner's syndrome is caused by a defect that cannot be detected by means employed in this study, and suggest that the defect is present at the steps distal to the autophosphorylation of tyrosine kinase of insulin receptors.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Humans; Insulin; Insulin Resistance; Male; Phosphorylation; Receptor, Insulin; Werner Syndrome

This paper reports our experience with the successful simultaneous transplantation of kidney and fetal pancreatic islets in 46-year-old diabetic man. No detectable C-peptide level was noted and the end-stage nephropathy required hemodialysis. The cadaver kidney and two masses of 8-week-cultured fetal islets were grafted simultaneously. After revascularization of the kidney, the islet masses were placed under the kidney capsule. Following transplantation, islet function was demonstrated by a higher C-peptide level, which subsequently persisted. Twenty-four months after grafting, islet function was provoked by glucagon and glucose, which led to elevations in the C-peptide and insulin levels. The insulin requirement fell from 58 to 24 U/day during the post-transplant period of 24 months. The mean value of HbA1C (5.6% +/- 0.3%) indicated a constantly normal carbohydrate metabolism. Improvements in retinopathy were also noted. Three periods of kidney rejection were diagnosed, but these proved reversible with high-dose steroid treatment. The serum and urine beta-2-microglobulin levels correlated well with rejection and recovery. More than 2 years after grafting, kidney functions is in the normal range. On sonography, the transplanted islet masses were repeatedly clearly visible, and 24 months following transplantation the volume was twice the original one. The results indicate that simultaneous kidney and fetal pancreatic islet grafting is advantageous in end-stage nephropathy secondary to type I diabetes mellitus.

Topics: C-Peptide; Diabetes Mellitus; Fetal Tissue Transplantation; Graft Survival; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Ultrasonography

Inasmuch as previous studies have obtained conflicting results on the contribution of obesity to insulin resistance in noninsulin-dependent diabetes mellitus (NIDDM), we studied 10 nonobese and 10 obese NIDDM patients with the isoglycemic-(approximately 10 mmol/L)-hyperinsulinemic clamp (two insulin infusions of 4 and 40 mU/m-2 min-1), combined with [3-3H]glucose infusion and indirect calorimetry. As compared with nonobese patients, obese NIDDM patients had higher baseline peripheral and estimated portal plasma insulin concentrations (113 +/- 18 vs. 46 +/- 3 pmol/L and 288 +/- 53 vs. 98 +/- 6 pmol/L, respectively; P < 0.05) and less suppressed endogenous insulin production during clamp. Hepatic glucose production was greater in obese than in nonobese patients (basal, 16 +/- 1.1 vs. 12 +/- 0.5 mumol/kg-1 fat-free mass (FFM) min-1; clamp, 5.7 +/- 0.5 vs. 2.8 +/- 0.2 mumol/kg-1 FFM min-1, P < 0.05). Glucose utilization increased to a lesser extent in obese than in nonobese patients (49 +/- 5 vs. 73 +/- 7 mumol/kg-1 FFM min-1, P < 0.05) during clamp because of a lower increase in nonoxidative glucose metabolism (30 +/- 5 vs. 50 +/- 7 mumol/kg-1 FFM min-1, P < 0.05). Plasma free fatty acid concentrations and rates of lipid oxidation were greater in obese (P < 0.05) patients and correlated with hepatic glucose production (r = 0.79 and 0.50, P < 0.05). In conclusion, obesity exaggerates hepatic as well as extra-hepatic insulin resistance in NIDDM. The impaired inhibition of pancreatic beta-cell function by exogenous insulin contributes to exaggerated hyperinsulinemia in obese NIDDM.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycolysis; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Obesity; Portal System; Regression Analysis

The function of the pancreatic incretory apparatus was studied in 51 patients with primary active pulmonary tuberculosis by analysing the blood levels of immunoreactive insulin, C peptide and glucose before and after glucagon stimulation. A pronounced enhanced insulin secretion was found. At the same time signs of relative insulin deficiency appeared as persistent hyperglycemia and apparently delayed concentration peaks of immunoreactive insulin and C peptide. Prednisolone therapy caused a noticeable, but rapidly reversible aggravation of relative insulin deficiency. Relative insulin deficiency coupled with the higher secretory function of the pancreatic insular apparatus which decreased its functional reserves with increases in the disease duration is likely to underlie the more frequent development of severe diabetes mellitus in patients with pulmonary tuberculosis.

Topics: Adult; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Tuberculosis, Pulmonary

Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Georgia; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values; Thinness

The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy.

Topics: Adult; Age of Onset; Biomarkers; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Glycated Hemoglobin; Humans; Incidence; Insulin; Male; Obesity; Proteinuria; Wisconsin

In persistent hyperinsulinemic hypoglycemia of infancy (PHHI), the long term outcome of the disease is not well documented. Previous reports suggested that partial pancreatectomy in infants does not endanger future islet function. We evaluated endocrine pancreatic function in 14 PHHI patients 6.5-21 yr after diagnosis. Eight underwent early subtotal pancreatectomy, and 6 were medically treated; all were in clinical remission. Intravenous glucose tolerance and C-peptide suppression tests were performed, with multiple determinations of hormone levels. The insulin response to glucose was blunted in all pancreatectomized and in 2 conservatively treated patients. Glucose disposal was reduced in 6 pancreatectomized patients and in 2 medically treated subjects. Six of the pancreatectomized patients, including two with normal glucose disposal at first evaluation, developed overt diabetes during puberty. None in the medically treated group became diabetic; however, only 2 patients have reached puberty. C-Peptide suppression in response to hypoglycemia was inadequate in 4 of 5 pancreatectomized and 3 of 5 nonpancreatectomized patients studied. These results show that children with PHHI have impaired insulin responses to glucose and lack of suppressibility of endogenous insulin secretion several years after clinical remission. Thus, the beta-cell defect responsible for the disease in infancy is not corrected with time despite the disappearance of spontaneous hypoglycemia. Insulin secretion seems more disturbed in pancreatectomized patients; the majority develop insulin-requiring diabetes during puberty. An effort should be made to treat PHHI patients medically to avoid pancreatectomy; this may reduce the incidence of diabetes at puberty.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diazoxide; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Octreotide; Pancreatectomy; Pancreatic Diseases; Prospective Studies; Time Factors

To examine the contribution of obesity to insulin resistance and abnormalities of intracellular glucose and fat metabolism in NIDDM.. Glucose turnover measurements and indirect calorimetry were performed in 10 obese non-insulin-dependent diabetes mellitus (NIDDM) and 10 lean NIDDM subjects (body mass index 35.3 +/- 1.0 vs. 24.1 +/- 0.5 kg/m2, P < or = 0.001) in the basal state and during hyperinsulinemic (720 pmol.m-2.min-1) euglycemic (5.0-5.5 mmol/l) clamps.. Obese and lean NIDDM subjects demonstrated similar basal rates of glucose uptake (GU) (1.15 +/- 0.08 vs. 1.26 +/- 0.08 mmol/min, NS) as well as oxidative (0.49 +/- 0.07 vs. 0.53 +/- 0.05 mmol/min, NS) and nonoxidative (0.67 +/- 0.10 vs. 0.73 +/- 0.12 mmol/min, NS) glucose metabolism. During hyperinsulinemic glucose clamp studies, rates of GU were lower in obese NIDDM subjects (34.1 +/- 2.3 vs. 55.2 +/- 3.8 mumol.kg fat-free mass [FFM]-1.min-1, P < or = 0.001) as were rates of oxidative (14.1 +/- 1.3 vs. 22.1 +/- 2.1 mumol.kg FFM-1.min-1, P < or = 0.005) and nonoxidative (20.0 +/- 2.3 vs. 33.1 +/- 3.6 mumol.kg FFM-1. min-1, P < or = 0.01) glucose metabolism. Although absolute rates of insulin-stimulated GU were decreased in the obese group, the relative distribution into glucose oxidation (GOX) and nonoxidative glucose metabolism (NOX) was comparable in both groups (GOX 42% in obese and 41% in lean subjects; NOX 58% in obese and 59% in lean subjects). The NIDDM groups had similar basal free fatty acid levels that were suppressed equally during hyperinsulinemic clamps. However, basal fat oxidation (Fox) was greater in the obese NIDDM group (103 +/- 11 vs. 73 +/- 8 mumol/min, P < or = 0.05) and was less suppressed to insulin (74 +/- 13 vs. 16 +/- 3 mumol/min, P < or = 0.001).. These results indicate that when obesity is present in NIDDM subjects with this degree of hyperglycemia, insulin-stimulated GU is lower by 35-40%. Reduced GU in obese NIDDM subjects leads to decreased intracellular substrate availability and lower rates of oxidative and nonoxidative glucose metabolism. Insulin suppression of Fox is also impaired when obesity is present and may contribute to decreased insulin-mediated GU in NIDDM. We conclude that obesity increases insulin resistance in NIDDM primarily by effects on GU rather than the intracellular pathways of glucose metabolism.

Topics: Adipose Tissue; Blood Glucose; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Lactates; Liver; Male; Middle Aged; Obesity; Oxidation-Reduction; Proteins; Thinness

Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects 'at risk' of diabetes (spot blood glucose level >6.0 mmol/l <2 h post cibum, or>4.6 mmol/l >2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched 'low-risk' control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95% of at-risk and 80% of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D <11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, imparied glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlation of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were -0.31 (p=0.04), 0.59 (p=0.0001) and 0.44 (p=0.006). In 15 'not-at-risk' subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r=0.39 (p=0.04) and 0.16 (p=0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p=0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p=0.7). Following treatment with 100,000 IU vitamin D by i.m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8-12 weeks later [mean +/- DS] from 57 +/- 62 to 96.2 +/- 82.4 mU/l [p=0.0017], 1.0 +/- 0.4 to 1.7 +/- 0.8 pmol/ml [p=0.001] and 3.6 +/- 1.8 to 13.5 +/- 7.4 ng/ml [p=0.0001], (but not to low-risk group values of 179 +/- mU/l, 2.7 +/- 1.14 pmol/ml and 8.16 +/- 6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1 +/- 8.22 (from 44 to 55 IU/l) and 0.15 +/- 0.18, (2.43 to 2.57 mmol/l), respectively (p=0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common.

Topics: Asian People; Bangladesh; Blood Glucose; C-Peptide; Calcifediol; Calcitriol; Diabetes Mellitus; Glucose Intolerance; Humans; Insulin; Insulin Secretion; London; Prevalence; Proinsulin; Reference Values; Regression Analysis; Risk Factors; Statistics, Nonparametric; Vitamin D Deficiency; White People

Topics: Age Factors; Aged; Analysis of Variance; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glucagon; Humans; Insulin; Insulin Secretion; Male; Morbidity; Myocardial Ischemia; Obesity; Risk Factors; Sex Factors

In the present series of 204 patients with NIDDM, 37 were lean and 35 obese. Mean FBG and HbA1C were significantly higher (P<0.02 and <0.01) in the former. Serum lipids such as total cholesterol (Tc) and triglycerides (Tg) were lower (P<0.05) in the lean while HDLc values were similar. Eight lean patients and 6 obese (Mean BMI : 15.7 vs.27.4) having similar age (48.0 vs 47.7 years) and mean duration of diabetes (4.6 vs 4.2 years) were subjected to the study of insulin and C-peptide status as well as beta cell reserve. The mean basal serum insulin (IRI) level was lower in the lean (15.3 vs. 28.9 mu u/ml ; P<0.05) while there was no statistical difference in the basal C-peptide values. Serum samples analysed 2 hours after 75 G of oral glucose and 1 mg I.V. glucagon (Novo) on two consecutive occasions for IRI and C-peptide responses revealed remarkable differences. The rise in IRI was significantly lower (p<0.01) in the lean after oral glucose and glucagon as compared to the obese. But the C-peptide values did not reveal significant difference suggesting similar reserve in beta cell function in both these groups of patients with NIDDM. The disparity between IRI and C-peptide levels observed was most likely due to excess extraction of insulin by the liver in lean-NIDDM, leading to lower peripheral levels. This phenomenon accounts for the occurrence of severe hyperglycemia inspite of good beta cell function in lean NIDDM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Glycated Hemoglobin; Humans; India; Insulin; Islets of Langerhans; Lipids; Male; Middle Aged; Obesity; Pilot Projects; Thinness

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; C-Peptide; Carrier Proteins; Diabetes Mellitus; Growth Disorders; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Syndrome

To solve a possible relationship between mtDNA mutation of tRNALYS(8344) and diabetes, we have surveyed the tRNALYS mutation, glucose intolerance, and insulin secretory capacity in a Japanese family with diabetes and myoclonic epilepsy with ragged-red fiber disease. Several lines of evidence suggested possible linkage between mtDNA mutation and diabetes (1-4).. DNA was isolated from peripheral lymphocytes. The polymerase chain reaction analysis for the tRNA(LYS)(8344) mutation of the mtDNA was conducted as described by Larsson (5). Insulin secretory capacity was assessed by 24-h urinary C-peptide immunoreactivity response (CPR) excretion and plasma CPR to glucagon administration.. We identified seven subjects with the tRNA(LYS) mutation as well as seven non-mutated members in the pedigrees. Oral glucose tolerance tests in the pedigree indicated that five of the mutated subjects were diabetic, one had impaired glucose tolerance, and one had normal glucose tolerance (NGT), whereas all nonmutated family members had NGT. The pedigree shows maternal transmission of diabetes and the tRNA(LYS) mutation over three generations. Twenty-four-hour urinary excretion of CPR was significantly reduced in the mutant subjects (mean +/- SD, 67.8 +/- 79.2 nmol/day, n = 6, P < 0.001) compared with the nonmutant members (276.6 +/- 41.8 nmol/day, n = 5) and the age-matched normal control subjects (263 +/- 64.3 nmol/day, n = 12). Plasma CPR 6 min after glucagon injection demonstrated a marked reduction in the mutant subjects (3.68 +/- 3.45 nmol/l, n = 5, P < 0.001) compared with the nonmutant members (19.4 +/- 1.17 nmol/l, n = 5) and the normal control subjects (15.8 +/- 3.81 nmol/l, n = 12). Bilateral neurosensory deafness was demonstrated in five of seven (71.4%) mutant subjects (five of five [100%] mutated diabetic patients), but not detected in six nonmutant members.. This observation is the first report of association of diabetes with the mitochondrial tRNA(LYS) mutation. Insulin secretory capacity was significantly lower in the mutant members than in the nonmutated members. These findings suggest that the pancreatic beta-cell secretory defect of insulin might be one of the phenotypes of the mitochondrial tRNA(LYS) mutation.

Topics: Adult; Blood Glucose; C-Peptide; Data Collection; Diabetes Complications; Diabetes Mellitus; Female; Humans; Insulin; Insulin Secretion; Japan; Male; MERRF Syndrome; Mitochondria; Pedigree; Point Mutation; Polymerase Chain Reaction; Radioimmunoassay; RNA, Transfer, Amino Acyl

Topics: Animals; C-Peptide; Cell Survival; Diabetes Mellitus; Fetus; Graft Survival; Humans; Immunosuppressive Agents; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Pilot Projects; Swine; Transplantation, Heterologous

Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric mixed diet. Subjects were then placed on caloric restriction for at least 6 weeks, during which time body weight fell by at least 10%. Refeeding with solid mixed meals was then resumed for at least 2 weeks until isocaloric intake was attained, and then the meal profiles were repeated. Before weight loss, insulin, C-peptide, and insulin secretion rates were significantly higher in subjects with subclinical diabetes than in the other two groups. Proinsulin concentrations were significantly greater in the two diabetic groups than in control subjects, but, when expressed as a percentage of the total insulin immunoreactivity, the differences were significant only in the group with overt diabetes. Weight loss because of hypocaloric feeding resulted in a significant increase in the rate of clearance of endogenously secreted insulin but did not affect the clearance of C-peptide. In obese subjects and those with subclinical diabetes, weight loss was associated with a reduction in insulin secretion rates, presumably as a result of improvements in insulin sensitivity. In patients with overt diabetes and hyperglycemia, weight loss improved beta-cell responsiveness to glucose and was associated with an increase in insulin clearance and a reduction in proinsulin immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Humans; Insulin; Metabolic Clearance Rate; Middle Aged; Obesity; Proinsulin; Reference Values; Weight Loss

The effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic females were compared during a 12-wk period. The first diet (n = 15) was designed to evoke a low insulin response (ID), and the second (n = 15) was a conventionally balanced diet (ND). After a 12-wk washout period, seven and nine subjects who had been on the ID and ND, respectively, changed to the alternative diet for 12 wk. Variables studied were basal and 30- and 120-min concentrations of blood glucose, insulin, and C-peptide after an oral glucose load; body weight; and energy intake. Mean (+/- SD) weight was significantly reduced after ID and ND (9.35 +/- 2.49 and 7.41 +/- 4.23, respectively). The mean weight loss was more after ID. Fasting insulin concentrations decreased more after ID compared with ND (91.3 +/- 61.8 vs 21.0 +/- 71.5 pmol/L; P < 0.05). We conclude that ID significantly reduces serum insulin concentrations and weight in obese hyperinsulinemic females.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Energy Intake; Fasting; Female; Humans; Hyperinsulinism; Insulin; Obesity; Weight Loss

Topics: Animals; C-Peptide; Capsules; Diabetes Mellitus; Glucose Tolerance Test; Insulin; Insulin Secretion; Islets of Langerhans Transplantation; Macaca fascicularis; Monkey Diseases; Swine; Transplantation, Heterologous

Very Low Calorie Diet (VLCD) is known to induce not only weight loss, but also an improvement of metabolic control, in obese type II diabetics. In order to evaluate the therapeutical efficacy of cycles of VLCD shorter than those previously described, 29 obese type II diabetics and 31 obese nondiabetic subjects were entered as inpatients and prescribed a 450 kcal/day diet for 15 days. Metabolic results obtained were similar to those achieved with longer cycles of VLCD, showing that 15 days are sufficient to induce a BMI decrease in diabetic (BMI from 35.3 +/- 4.8 to 33.3 +/- 4.6 after VLCD) and nondiabetic patients (BMI from 40.5 +/- 7.4 to 38.1 +/- 7.2 after VLCD), a desired fall of blood glucose levels and the decrease of daily insulin needs in insulin-treated patients. Glucagon tests were performed before and after VLCD in order to study possible modifications of insulin secretion. Although we did not observe any significant increase of C-peptide basal or peak levels (nM/ml) either in diabetic (basal levels before VLDC: 1.2 +/- 0.4 and peak levels 2.4 +/- 0.7; basal after VLCD 1.23 +/- 0.6 and peak 2.6 +/- 0.7) and nondiabetic patients (basal levels before VLDC 1.0 +/- 0.3 and peak levels 2.5 +/- 0.4; basal after VLCD 0.9 +/- 0.3 and peak 2.4 +/- 0.6). The rise of the C-peptide/glycemia ratio is an index of an improvement of insulin biological activity, which could be partly responsible for the therapeutical effects of VLCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Receptor, Insulin; Weight Loss

Glucose intolerance and diabetes mellitus are both prevalent in cirrhosis, yet the pathogenesis of impaired glucose metabolism remains unknown. Therefore insulin secretion (hyperglycemic clamp, +125 mg/dl), insulin sensitivity (euglycemic hyperinsulinemic insulin clamp, +10 microU/ml and +50 microU/ml), whole-body glucose oxidation (indirect calorimetry) and glucose turnover ([6,6-2H2]glucose isotope dilution) were evaluated in a homogenous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 6). The results were compared with those obtained in control subjects (n = 8). In glucose-intolerant patients, whole-body glucose uptake (mainly reflecting glucose utilization by muscle) was significantly impaired in patients during both insulin infusions as a result of decreased stimulation of the two major intracellular pathways of glucose disposal--nonoxidative glucose disposal (i.e., glycogen synthesis) and glucose oxidation. Hepatic glucose production was normal in the basal state and was normally suppressed during stepwise insulin infusion (by 65% and 85%, respectively, p = NS vs. controls). Hyperglycemia-induced increases of plasma C-peptide concentrations were comparable to those in controls (p = NS). In diabetic patients, insulin-mediated glucose uptake was significantly reduced, mainly because of impaired non-oxidative glucose disposal. Glucose oxidation appeared to be reduced, too. Hepatic glucose production was significantly increased in the basal state (3.03 +/- 0.24 vs. 2.34 +/- 0.10 mg/kg min, p < 0.02) and during insulin infusion (+50 microU/ml: 0.67 +/- 0.17 vs. 0.13 +/- 0.08 mg/kg min, p < 0.05) compared with that in controls. Both the first and second phases of beta-cell secretion were significantly reduced in response to steady-state hyperglycemia (both p < 0.01 vs. control values). In conclusion, glucose intolerance in cirrhosis results from two abnormalities that occur simultaneously: (a) insulin resistance of muscle and (b) an inadequate response (even when comparable to that of controls) of the beta-cells to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulin-resistant cirrhotic patients develops as the result of progressive impairment in insulin secretion together with the development of hepatic insulin resistance leading to fasting hyperglycemia and a diabetic glucose tolerance profile.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Glucose Clamp Technique; Glucose Intolerance; Humans; Hyperglycemia; Insulin; Lactates; Lactic Acid; Liver Cirrhosis; Male; Middle Aged; Reference Values

Accelerated atherosclerosis is the leading cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic activity may accelerate atherosclerosis by exposing vascular luminal wall surfaces to persistent and recurrent thrombi and clot-associated mitogens. This study was conducted to further characterize endogenous fibrinolysis in lean and obese nondiabetic subjects and in NIDDM patients and to identify mechanisms responsible for the alterations identified. Obese and diabetic subjects had threefold elevations of plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of significant differences in plasma concentrations of tissue-type plasminogen activator in the obese and diabetic subjects, both basal and stimulated endogenous fibrinolytic activities were decreased. The decreases were associated with increased activity of PAI-1 in plasma, in turn correlated with increased concentrations of immunoreactive insulin and C-peptide. These results are consistent with our previous observations demonstrating direct stimulatory effects of insulin and its precursors on cellular expression of PAI-1 in vitro and observations by others demonstrating decreased basal fibrinolytic activity in NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged or recurrent exposure of luminal surfaces of vessel walls to microthrombi and clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic subjects.

Topics: Adult; Analysis of Variance; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysis; Humans; Insulin; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Reference Values; Tissue Plasminogen Activator

The diabetes mellitus that occurs in patients with pancreatic cancer is characterized by marked insulin resistance that declines after tumor resection. Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis in vitro. In this study, we examined the relation between IAPP and diabetes in patients with pancreatic cancer.. We measured IAPP in plasma from 30 patients with pancreatic cancer, 46 patients with other cancers, 23 patients with diabetes, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger RNA were studied in pancreatic cancers, pancreatic tissue adjacent to cancers, and normal pancreatic tissue.. Plasma IAPP concentrations were elevated in the patients with pancreatic cancer as compared with the normal subjects (mean [+/- SD], 22.3 +/- 13.6 vs. 8.0 +/- 5.0 pmol per liter; P < 0.001), normal in the patients with other cancers, and normal or low in the patients with diabetes. Among the patients with pancreatic cancer, the concentrations were 25.0 +/- 8.7 pmol per liter in the 7 patients with diabetes who required insulin, 31.4 +/- 12.6 pmol per liter in the 11 patients with diabetes who did not require insulin, and 12.2 +/- 2.4 pmol per liter in the 9 patients with normal glucose tolerance (3 patients had impaired glucose tolerance; their mean plasma IAPP concentration was 11.7 +/- 5.5 pmol per liter). Plasma IAPP concentrations decreased after surgery in the seven patients with pancreatic cancer who were studied before and after subtotal pancreatectomy (28.9 +/- 16.4 vs. 5.6 +/- 3.4 pmol per liter, P = 0.01). Pancreatic cancers contained IAPP, but the concentrations were lower than in normal pancreatic tissue (17 +/- 16 vs. 183 +/- 129 pmol per gram, P < 0.001). In samples from the patients with both pancreatic cancer and diabetes, immunostaining for IAPP was reduced in islets of pancreatic tissue surrounding the tumor; in situ hybridization studies suggested that transcription occurred normally in these islets.. Plasma IAPP concentrations are elevated in patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin resistance, its overproduction may contribute to the diabetes that occurs in these patients.

Topics: Aged; Amyloid; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Humans; Insulin Resistance; Islet Amyloid Polypeptide; Male; Middle Aged; Pancreatic Neoplasms; RNA, Messenger; RNA, Neoplasm

Immunohistochemical studies of pancreatic tissue from patients with cystic fibrosis associated with diabetes mellitus (CFDM) show increased numbers of somatostatin secreting delta cells. To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured. Mean basal somatostatin concentrations were not different in the two groups. Mean peak somatostatin concentrations were significantly higher in the group with CFDM: 11.60 pmol/l v 7.14 pmol/l in controls. Mean peak C peptide concentrations were significantly lower in the group with cystic fibrosis: 0.89 nmol/l v 4.27 nmol/l in controls. This observation provides a physiological correlate to the pathological finding of increased somatostatin content in pancreatic tissue from patients with CFDM. Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.

Topics: Adult; C-Peptide; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Female; Humans; Immunohistochemistry; Islets of Langerhans; Male; Pancreas; Somatostatin

To investigate glucose metabolism and insulin secretion on patients with pancreatic cancer compared with healthy control subjects.. Open study.. Linköping University Hospital, Sweden.. 44 consecutive patients referred for radical operations for pancreatic carcinoma, and eight healthy age and sex matched volunteers.. Hyperglycaemic glucose clamp in 36 of patients and all volunteers.. Glucose tolerance according to WHO criteria, plasma insulin and C-peptide concentrations, and insulin secretion measurements both during hyperglycaemia and after stimulation by glucagon.. Thirty-three patients (75%) had either impaired glucose tolerance or diabetes. Fasting insulin concentrations were raised in the non-insulin-requiring diabetic patients, but similar in the insulin-requiring group compared with healthy control subjects and patients with normal glucose tolerance. In neither diabetic group was insulin secretion affected during hyperglycaemia. After stimulation with glucagon, insulin secretion increased in non-insulin-requiring diabetic patients but remained unchanged in those who required insulin. Glucose metabolic capacity and whole body insulin sensitivity were reduced in patients with diabetes and with impaired glucose tolerance, and the reduction was more pronounced in diabetic patients.. There is a high incidence of impaired glucose tolerance and diabetes in patients with pancreatic cancer, which cannot be explained by impaired secretion of insulin. Other factors that reduce insulin sensitivity seem to have a role in the development of diabetes in this group of patients.

Topics: Adenocarcinoma; Aged; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms

We have studied the pharmacokinetics and pharmacodynamics of glyburide during long-term therapy in 20 patients with type II diabetes mellitus. The patients were divided according to body mass index (BMI) into an obese group [n = 12, age 55(13) y, BMI 36.2(9.2) kg.m-2, total body weight (TBW) 100(23) kg], and a non-obese group [n = 8, age 61(13) y, BMI 24.5(2.1) kg.m-2, TBW 73(7) kg]. The dosages of glyburide were titrated to achieve specified therapeutic goals based upon serum glucose concentrations or to a maximum dosage of 20 mg per day. The pharmacokinetics of glyburide were determined at week 12 of treatment. On the study day, the patients took a 2.5 mg liquid test dose of glyburide with a Sustacal meal challenge. The elimination rate constant (lambda z), clearance (CL), and apparent volume of distribution (Vz) were 0.08 h-1, 3.3 l.h-1, and 47.0 l in the obese group, and 0.07 h-1, 3.1 l.h-1, and 56.8 l in the non-obese group. These values were not statistically significantly different. However, there were differences between the groups when the volume and clearance were corrected by TBW or BMI but not by ideal body weight (IBW) or fat-free mass (FFM). Regression analysis between the pharmacokinetic variables and body weight status revealed statistically significant correlations between volume or clearance and body weight. However, due to large inter-patient variability, these relations were relatively weak and were considered to be non-predictive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Insulin; Male; Middle Aged; Obesity; Time Factors

The examination of 170 patients with chronic alcohol pancreatitis revealed diabetes mellitus (DM) in 21% of them. It manifested with polydipsia, polyuria and weight loss along with pancreatitis symptoms. DM complications were rare. Exercise tests were indicative of reduced insulin and glycagon reserves in the majority of the examinees. This condition depended on pancreatitis severity. DM in pancreatitis presents a high risk of hypoglycemia which should be taken into consideration when designing schemes of relevant treatment.

Topics: Adult; Alcoholism; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Glucose; Humans; Insulin; Islets of Langerhans; Male; Pancreatitis; Time Factors

To explore the associations between blood pressure and both fasting insulin and C-peptide levels.. A cross-sectional analysis was conducted of 895 normoglycemic members of a bi-ethnic community in Colorado who were selected from a control group recruited for a geographically based study of diabetes mellitus prevalence and risk factors. All subjects included in this study had normal glucose tolerance as judged by a 75-g oral glucose tolerance test interpreted using World Health Organization criteria. None of the subjects were taking antihypertensive medication. Multiple linear regression analysis was used to examine relationships between fasting insulin and C-peptide levels and blood pressure.. Among all subjects, diastolic blood pressure was found to significantly increase with increasing levels of both hormones (insulin coefficient = 0.197, P = 0.013; C-peptide coefficient = 0.0436, P = 0.004), whereas systolic blood pressure was significantly related to fasting C-peptide level (coefficient = 0.0295, P = 0.050). These relationships were similar in magnitude for both Hispanic and non-Hispanic white subjects, but were diminished among women and subjects with a higher body mass index.. Higher fasting insulin and C-peptide levels are associated with higher blood pressure, but these relationships are modified by sex and degree of obesity.

Topics: Adult; Age Factors; Aged; Blood Glucose; Blood Pressure; C-Peptide; Colorado; Cross-Sectional Studies; Diabetes Mellitus; Ethnicity; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Insulin; Male; Middle Aged; Prevalence; Regression Analysis; Risk Factors; Sex Factors; White People

Peripheral hyperinsulinism is said to be associated and perhaps implicated in the pathogenesis of hypertension. There is however some inconsistency in the evidence of the relationship between insulin and blood pressure. We prospectively investigated glucose metabolism, insulin and C-peptide values and serum lipids in a large sample of hypertensive as compared with age and body habitus-matched normotensive subjects. As a group, the 145 hypertensives (blood pressure: 160/99 +/- 8.5/6.5 mmHg, mean +/- SD) had significantly elevated fasting plasma insulin (p < 0.02), total and LDL-cholesterol (p < 0.01) than 132 normotensive control subjects. The fasting HbA1c (glycated hemoglobin A1c)/insulin ratio, an estimate of insulin sensitivity, was significantly lower (5.15 +/- 1.45) in the hypertensives than normotensives (5.8 +/- 1.5, p < 0.001). Hypertensives had normal fasting C-peptide levels and lower C-peptide/insulin molar ratios, indicating low hepatic insulin extraction. There was no correlation between mean blood pressure (1/3 systolic + 2/3 diastolic) and fasting serum C-peptide (p = 0.14), insulin (p = 0.11), HbA1c/insulin ratio (p = 0.6), C-peptide/insulin ratio (p = 0.22) and HbA1c (p = 0.19), even after adjusting for age, BMI and family history of diabetes. The differences between hypertensives and normotensives persisted after dividing the subjects according to the presence/absence of either obesity or impaired glucose tolerance, but the significance was lost due to the smaller samples of the subgroups. The obese hypertensives with impaired glucose tolerance had the lowest values of insulin sensitivity and clearance in the fasting state.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Secretion; Lipids; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Prospective Studies

Insulin resistance is a characteristic feature of glucose-intolerant and diabetic cirrhotic patients. The pathogenic factors, however, that are responsible for the development of impaired glucose tolerance in cirrhosis, remain unclear. To examine whether the ability of hyperglycemia per se to enhance glucose uptake (by means of mass-action effect) is impaired in cirrhosis, we measured (insulin-independent) whole-body glucose disposal during hyperglycemia (hyperglycemic clamp studies, +125 mg/dl, in combination with an infusion of somatostatin (500 micrograms/hr), insulin (0.1 mU/kg min) and glucagon (0.5 ng/kg min) to "clamp" hormone levels at baseline), whole-body glucose oxidation (indirect calorimetry) and glucose turnover (prime-continuous infusion of [6,6-2H2-]glucose in a clinically homogeneous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 7) and in control individuals (n = 7). Fasting plasma glucose concentrations were normal in glucose-intolerant patients but were significantly increased in diabetic patients (158 +/- 19 vs. 87 +/- 2 mg/dl in controls; p < 0.01). Plasma glucose concentrations were clamped at 214 +/- 4 mg/dl in controls, at 212 +/- 4 mg/dl in glucose-intolerant patients and at 287 +/- 19 mg/dl in diabetic patients; plasma insulin and glucagon concentrations were maintained at baseline levels. In the basal state, total-body glucose disposal (which equals basal hepatic glucose output) was normal in glucose-intolerant patients (2.25 +/- 0.11 mg/kg min) but was increased in diabetic patients compared with controls (3.32 +/- 0.26 mg/dl vs. 2.45 +/- 0.10 mg/dl; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Complications; Diabetes Mellitus; Drug Resistance; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Humans; Insulin; Lactates; Lactic Acid; Liver; Liver Cirrhosis; Male; Middle Aged; Osmolar Concentration; Oxidation-Reduction

Diabetes occurs frequently in patients with pancreatic cancer. To investigate the impact to tumour removal, seven patients were studied before and after 85 per cent subtotal pancreatectomy for adenocarcinoma of the pancreas. The frequency of diabetes was determined by the oral glucose tolerance test. Fasting levels of C peptide and insulin were measured in plasma, and insulin secretion was investigated by hyperglycaemic glucose clamp and glucagon stimulation. Six of the seven patients were diabetic before surgery and four required insulin treatment. Improvements in diabetic status and glucose metabolism were found in all seven patients after operation, as demonstrated by increased glucose metabolic capacity during hyperglycaemia. This occurred despite a postoperative reduction in insulin secretion and is explained by the observed augmentation of whole-body insulin sensitivity after surgery. A diabetogenic factor may be produced by pancreatic adenocarcinoma that may be responsible, directly or indirectly, for the high frequency of diabetes in patients with pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Postoperative Period

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24-59) years, IGT 48 (29-64) years, diabetic 43 (29-60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m-2 (17.2-29.9), IGT 26.0 kg m-2 (19.8-33.9), diabetic 24.2 kg m-2 (19.3-32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70-0.98), IGT 0.88 (0.75-0.98), diabetic 0.89 (0.75-1.00)). Blood pressure was significantly higher in both IGT (systolic 127 mmHg (108-162), diastolic 84 mmHg (66-99)) and diabetic patients (systolic 130 mmHg (104-160), diastolic 84 mmHg (66-102)) compared to non-diabetic controls (systolic 120 mmHg (100-151), diastolic 80 mmHg (60-94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r = approximately 0.25, p < 0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r = 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r = 0.30, p < 0.001, post glucose r = approximately 0.20, p < 0.05) but not to C-peptide concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diastole; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Obesity; Systole

In cirrhotic patients with normal fasting glucose levels both insulin insensitivity and a blunted early insulin response to oral glucose are important determinants of the degree of intolerance to oral glucose. It is not known whether the ability of hyperglycaemia per se to enhance glucose disposal (glucose effectiveness) is also impaired. It is also unclear whether overt diabetes is due to: (1) more marked insulin insensitivity; (2) impaired insulin secretion; (3) reduced glucose effectiveness; or (4) a combination of these mechanisms. We used the "minimal model" to analyse the results of a 3-h intravenous glucose tolerance test to assess glucose effectiveness, insulin sensitivity and insulin responses in 12 non-diabetic cirrhotic patients, 8 diabetic cirrhotic patients and 10 normal control subjects. Fasting blood glucose levels were 4.8 +/- 0.2, 7.5 +/- 0.6 and 4.7 +/- 0.1 mmol/l, respectively. Fasting insulin and C-peptide levels were higher in both cirrhotic patient groups compared with control subjects. The glucose clearance between 6 and 19 min after i.v. glucose was lower in both cirrhotic groups (non-diabetic, 1.56 +/- 0.14, diabetic, 0.76 +/- 0.06, control subjects, 2.49 +/- 0.16 min-1%, both p < 0.001 vs control subjects). Serum insulin peaked at 3 and 23 min in the non-diabetic cirrhotic patients and control subjects; both peaks were higher in the non-diabetic cirrhotic patients and showed a delayed return to basal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Insulin Resistance; Liver Cirrhosis; Middle Aged; Tolbutamide

Pancreatic and gut hormone responses to oral glucose, and insulin sensitivity were studied in cystic fibrosis patients with normal (N = 14), impaired (N = 4), and diabetic (N = 12) glucose tolerance, and in 10 control subjects, and beta cell responses to oral glucose and intravenous glucagon were compared. Compared to control subjects, initial insulin and C-peptide responses to oral glucose were lower in all patient groups, and decreased with decreasing glucose tolerance. Insulin sensitivity in patients with impaired and diabetic glucose tolerance was lower than in control subjects. The 6 min post-glucagon C-peptide concentration was positively correlated with the initial insulin response to oral glucose. Fasting levels of pancreatic polypeptide, pancreatic glucagon, total glucagon, glucagon-like peptide-1 7-36 amide, and gastric inhibitory polypeptide were normal in all patient groups. Following oral glucose, pancreatic polypeptide responses were absent in all patients, suppressibility of pancreatic glucagon secretion was increasingly impaired with decreasing glucose tolerance, and gut hormone levels were normal. In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact.

Topics: Administration, Oral; Adult; C-Peptide; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Glucose Tolerance Test; Hormones; Humans; Injections, Intravenous; Insulin; Intestinal Mucosa; Intestines; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Peptide Fragments; Proinsulin; Protein Precursors; Time Factors

Acetate is a short-chain fatty acid derived from colonic fermentation of carbohydrate and dietary fiber, and from endogenous glucose and fatty acid metabolism in the liver. An impaired acetate metabolism has been reported in diabetic subjects. The aim of the study was to evaluate plasma acetate levels in a group of obese diabetic subjects, compared with obese normoglycemic subjects and normal control subjects. Eleven noninsulin-dependent diabetic patients taking oral antidiabetic drugs, eight obese normoglycemic subjects, and seven control subjects were studied. Liver, kidney, and gut functions were normal in all subjects. Blood acetate, glucose, insulin, and C-peptide were evaluated in all subjects. Acetate levels were significantly higher in the diabetic subjects than in obese normoglycemic and normal subjects. Significant correlations between HbA1c, glucose, and acetate levels, but not between acetate and C-peptide or insulin, were also observed.

Topics: Acetates; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Lipids; Middle Aged; Obesity

Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations. Its effects in patients with diabetes mellitus are not known.. We compared the effect of an infusion of GLIP that raised plasma concentrations of GLIP twofold with the effect of an infusion of saline, on the meal-related release of insulin, glucagon, and somatostatin in eight normal subjects, nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus (IDDM). The blood glucose concentrations in the patients with diabetes were controlled by a closed-loop insulin-infusion system (artificial pancreas) during the infusion of each agent, allowing measurement of the meal-related requirement for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity.. In the normal subjects, the infusion of GLIP significantly lowered the meal-related increases in the blood glucose concentration (P less than 0.01) and the plasma concentrations of insulin and glucagon (P less than 0.05 for both comparisons). The insulinogenic index (the ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P less than 0.001), so that the integrated area under the curve for plasma free insulin was decreased (P less than 0.05) in spite of the stimulation of insulin release. In the patients with IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and somatostatin release in both groups of patients. In the normoglycemic-clamp studies in the patients with IDDM, the GLIP infusion significantly increased glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram of body weight per minute; P less than 0.01).. GLIP has an antidiabetogenic effect, and it may therefore be useful in the treatment of patients with NIDDM:

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Eating; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Infusion Systems; Insulin Secretion; Male; Middle Aged; Obesity; Peptide Fragments; Peptides; Somatostatin

An epidemiologic study of end-stage diabetic nephropathy in France (Uremidiab) was performed, aiming to establish the prevalence of both types of diabetes in dialysis patients. Because discrimination between type I and type II diabetes remains mostly clinical, our aim was to evaluate what the most fitted clinical criteria were. We studied 494 hemodialyzed diabetic patients. A first classification (Cn) was offered by the nephrologist. Clinical data of 472 patients (22 patients of the 494 have been excluded) were then collected with a standardized questionnaire, allowing one diabetologist of us to establish the diagnosis of type of diabetes (classification Cd). Plasma C-peptide at this stage of the disease was expected to be very discriminative, measured in 88 patients and defined classification Ccp (< or = 0.6 ng/ml = "negative C-peptide" = type I, > 0.6 ng/ml = "positive C-peptide" = type II). Classification Cd observed 98 type I and 374 type II diabetes. Cn overestimated type I diabetes, 37% of type II diabetes being misclassified because insulin-treated. Classification Ccp observed 74 positive C-peptide patients, classified as type II, among whom 45 were insulin-treated. Only 3 patients were discordant for classification Cd and Ccp. Predictive value of "negative C-peptide" and "positive C-peptide" were 100% and 96% respectively. Multiple regression analysis of the Ccp classification was performed with the clinical criteria and showed very significant correlation with: age at the time of diagnosis of diabetes (AGE), maximal body mass index ever reached (BMI MAX) and delay between diagnosis and consistent insulin use (DI).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetic Nephropathies; Fasting; Female; France; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Reproducibility of Results; Retrospective Studies

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adult; Blood Pressure; C-Peptide; Cholesterol; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Hip; Humans; Hyperinsulinism; Insulin; Islets of Langerhans; Liver; Male; Models, Biological; Obesity; Time Factors; Triglycerides

OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.

Topics: Adult; Albuminuria; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Pancreatic Diseases; Regional Blood Flow; Renal Circulation

Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110 +/- 11 to 183 +/- 23 mg.m-2.min-1 (p less than 0.03); control subjects: 219 +/- 23 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetes). Non-oxidative glucose disposal increased from 74 +/- 17 to 138 +/- 19 mg.m-2.min-1 (p less than 0.03), control subjects: 159 +/- 22 mg.m-2.min-1 (p = NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58 +/- 0.54 to 3.35 +/- 0.23 mumol.l-1.min-1 (p less than 0.05), control subjects: 2.99 +/- 0.86 mumol.l-1.min-1 (p = NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r = 0.97, p less than 0.001), reductions in serum fructosamine (r = 0.77, p less than 0.05), and weight loss (r = 0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Calorimetry; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Fatty Acids, Nonesterified; Female; Fructosamine; Glycogen Synthase; Hexosamines; Humans; Insulin; Male; Muscles; Obesity; Receptor, Insulin; Reference Values

Topics: C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Antibodies; Male; Middle Aged; Pancreas

Islet amyloid polypeptide (IAPP/Amylin) is a novel peptide which was extracted from islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus (NIDDM). However, its pattern of secretions and plasma concentrations under various conditions has not yet been made clear enough. In this study, we examined IAPP secretion from islet beta-cells in vitro using cultured islet cells of neonatal rat pancreas and plasma IAPP responses under various conditions in vivo in normal control subjects and patients with glucose intolerance. Our data revealed that (1) IAPP is co-secreted with insulin from islet cells of the rat pancreas by glucose and non-glucose stimuli; (2) fasting plasma IAPP levels in normal control subjects are 24.9 +/- 2.0 pg/ml and the molar ratio of IAPP/insulin is approximately 1/7; (3) fasting IAPP levels are high in obese patients and low in insulin-dependent diabetic patients, and the molar ratio of IAPP/C-peptide in NIDDM patients is lower than that in normal control subjects, suggesting the basal hyposecretion of IAPP relative to insulin in NIDDM; and (4) the obese patients who had a hyperresponsiveness of insulin relative to C-peptide had the hyperresponsiveness of IAPP relative to C-peptide during an oral glucose load, suggesting that IAPP may have some physiological effect in glucose metabolism.

Topics: Adult; Amyloid; Animals; Animals, Newborn; Blood Glucose; C-Peptide; Cells, Cultured; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Islet Amyloid Polypeptide; Islets of Langerhans; Middle Aged; Obesity; Rats; Reference Values

To evaluate insulin receptor binding characteristics of urbanized South African black women with normal glucose tolerance and of patients with newly diagnosed untreated non-insulin-dependent diabetes mellitus (NIDDM).. Four groups of 10 subjects each were selected by the following criteria: group A, young (20-39 yr) nonobese (body mass index [BMI] 19.0-24.9 kg/m2) nondiabetic women; group B, middle-aged (40-60 yr) nonobese nondiabetic women; group C, middle-aged obese (BMI greater than 30.0 kg/m2) nondiabetic women; and group D, middle-aged obese newly diagnosed but untreated female patients with NIDDM. Insulin binding to monocyte receptors was determined by radioreceptor assay. Fasting plasma samples were analyzed for glucose, insulin, C-peptide, and nonesterified fatty acids.. In the four groups studied, maximum specific binding and receptor concentration were highest in group A, with a progressive and significant decrease in values through groups B and C to group D. Significant inverse correlations were obtained between maximum specific binding, 50% inhibition dose, and total receptor concentration on the one hand and glucose, insulin, and NEFA on the other.. Our study of urban South African black women showed decreasing insulin-receptor activity with obesity and glucose intolerance. In patients with NIDDM, hyperglycemia and beta-cell dysfunction were associated with a reduction in receptor concentration. In this regard, our findings in South African blacks are consistent with results of similar studies of NIDDM in other communities.

Topics: Adult; Age Factors; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Humans; Insulin; Middle Aged; Monocytes; Obesity; Receptor, Insulin; Reference Values; South Africa; Urban Population

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fatty Acids, Nonesterified; Female; Glucagon; Glucose Tolerance Test; Glycerol; Growth Hormone; Humans; Hydrocortisone; Hydroxybutyrates; Male; Multivariate Analysis; Pancreas; Reference Values; Triglycerides

There are few reports on the genetic, immunological and nutritional characteristics of insulin-using youth-onset diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) and malnutrition-related diabetes mellitus (MRDM) in Korea. Among 1266 hospitalized Korean diabetics, 29 (2.3%) were IDDM and 84 (6.6%) were MRDM. A diabetes history of first-relatives (28.6%) was more frequently found in the MRDM group than in the IDDM (14.8) and non-insulin-dependent diabetes mellitus (NIDDM) (19.0%) groups. HLA-DR4 was more common among IDDM (54.2%) and MRDM (52.4%) patients than controls (26.3%), and HLA-DR3 was more common among only IDDM patients (29.2%) than controls (10.9%). Conventional islet-cell antibodies were detected in 8 of 15 IDDM patients tested (53.3%) and in 11 of 22 MRDM patients (50.0%). MRDM patients had higher serum basal (1.02 +/- 0.51 ng/ml) and peak (1.44 +/- 0.76 ng/ml) C-peptide concentrations than IDDM patients, but lower concentrations than NIDDM patients. Before the onset of diabetes, the calorie intake of 21 MRDM patients assessed was 63.1% of the daily requirement and the intake of carbohydrate, protein and fat was 71.7%, 55.9% and 39.8%, respectively. In summary, our data suggest that IDDM in Korea is associated with HLA-DR3 or HLA-DR4, indicating a risk for IDDM in Western societies; furthermore, MRDM has a history of undernutrition at the preonset period and is also associated with HLA-DR4. It might be also concluded that MRDM in Korea is another expression of IDDM caused by the shortage of some nutrients for the structural and/or functional maintenance of pancreatic beta-cells.

Topics: Adolescent; Autoantibodies; Blood Glucose; Blood Proteins; C-Peptide; Cholesterol, HDL; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diet; Female; Glucose Tolerance Test; Glycated Hemoglobin; HLA-DR Antigens; Humans; Islets of Langerhans; Korea; Male; Nutrition Disorders; Triglycerides; Vitamins

In order to assess hepatic glycogen stores in patients with noninsulin dependent diabetes mellitus (NIDDM) after a 3-day fast, the incremental glucose response to 1.0 mg iv glucagon (glucose area under the curve, glucoseAUC) was assessed in 19 obese diabetic subjects after an overnight (14 h) fast and again after a 3-day (64 h) fast. Results were compared to those of lean (n = 6) and obese (n = 15) nondiabetic subjects. During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. However, in contrast to the fall in glucoseAUC observed in the lean (92.4 +/- 15.4 to 39.9 +/- 8.1 mmol min-1 L-1, P less than 0.02) and obese (64.4 +/- 11.1 to 48.4 +/- 9.4 mmol min-1 L-1) subjects, the glucoseAUC increased in diabetic subjects from 81.6 +/- 8.6 to 103.9 +/- 8.8 mmol min-1 L-1 during the fast, and was significantly greater than that of either the lean (P less than 0.001) or obese (P less than 0.001) nondiabetic subjects after the 64-h fast. Evidence that the glucose response to glucagon after a 64-h fast represents glycogenolysis and not gluconeogenesis was provided by studies in 10 additional subjects (5 obese nondiabetic subjects and 5 patients with NIDDM). Overall hepatic glucose output calculated from glucose kinetic data [( 3-3H]glucose) increased in diabetic and nondiabetic subjects during the first 30 min after glucagon administration and fell progressively thereafter. However, no increase in alanine gluconeogenesis (14C-alanine incorporation into glucose) was observed after glucagon administration in either subject group. The paradoxical accumulation of glycogen in the patients with NIDDM during the fast occurred despite basal rates of hepatic glucose output on the third day of the fast which were greater than those of obese nondiabetic subjects (9.0 +/- 1.2 vs. 5.6 +/- 0.5 mumol kg-1 min-1, P less than 0.05). A glycogen sparing action of increased gluconeogenesis is proposed as the explanation for the preservation of liver glycogen in patients with NIDDM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Liver Glycogen; Male; Obesity; Reference Values

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Follow-Up Studies; Gliclazide; Glucose Clamp Technique; Humans; Insulin; Insulin Infusion Systems; Insulin Secretion; Middle Aged; Obesity

Several clinical and epidemiological evidences support the increased risk of cardiovascular disease (CVD) in pathological conditions as obesity, hypertension, non-insulin-dependent diabetes mellitus, which have hyperinsulinemia as a common feature. In this study, we assessed basal plasma insulin (IRI) and C-peptide (CPR) concentrations in 297 volunteers who participated in a survey concerning risk factors of CVD. We found a stepwise increase in fasting insulin and C-peptide levels in normal subjects (IRI 9.10 +/- 0.41 microU/ml; CPR 1.79 +/- 0.08 ng/ml), in obese subjects (IRI 11.31 +/- 0.38 microU/ml; CPR 2.54 +/- 0.07 ng/ml) in obese hypertensive subjects (IRI 14.17 +/- 0.72 microU/ml; CPR 2.64 +/- 0.09 ng/ml), in obese hypertensive diabetic subjects (IRI 22.57 +/- 2.62 microU/ml; CPR 3.33 +/- 0.27 ng/ml). Thus, we found increasing levels of IRI and CPR as normal conditions changed towards progressively more severe pathological conditions. Although several other factors contribute to determine CVD, we conclude that increasing levels of insulin and C-peptide could play an important role in causing CVD.

Topics: Adult; Biomarkers; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension; Insulin; Male; Medical History Taking; Middle Aged; Obesity; Risk Factors; Surveys and Questionnaires

The urinary excretion of chromium, copper and manganese was determined in 185 diabetics and in an equal number of control subjects by measuring the concentration of each of these metals using electrothermal atomic spectrophotometry and dividing the values by the urinary concentration of creatinine (creat) in each subject. The mean (SEM) values for the overall diabetics and the control group were 2.32 (0.17) and 2.62 (0.22) mumol Cr/mole of creat, 76.5 (5.5) and 73.9 (6.1) mumol Cu/mole of creat, and 3.56 (0.44) and 2.66 (0.3) mumol Mn/mole of creat, respectively. There was no correlation between the urinary excretion of any of the metals examined and age or sex of either group. While the cardiovascular or ophthalmologic diseases associated with diabetes did not influence the excretion of any of these metals, significantly higher urinary excretion of Cu was exhibited by diabetics with neuropathy (p < 0.0027) or infections (p < 0.014) than by those without. Also, diabetics with liver disorders or those who were not treated with insulin excreted significantly more Mn than did their diabetic counterparts.

Topics: C-Peptide; Chromium; Copper; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Liver Diseases; Male; Manganese; Middle Aged; Reference Values; Spectrophotometry, Atomic; Trace Elements

Over the last four years, we have done a prospective study of insulin requiring diabetes (IRD). We offered 59 patients insulin therapy during 10 to 14 days by means of continuous subcutaneous insulin injection with the help of a pump in order to maintain the patient under oral hypoglycemic agents (OHA). We divided our population into two characteristic groups and isolated parameters that were predictive of post-insulin therapy evolution by means of C peptide assays. In one group, in 50% of cases, endogenous insulin production appeared impaired and could not be restored by insulin therapy. The patients in this group suffered a renewed drug failure within 3 months. In the other group, 50% of cases, endogenous insulin production was preserved and the CP/blood glucose level ratio improved. On insulin treatment interruption, we observed a significantly improved fasting blood glucose level and we observed decreased insulin needs. The patients, who were probably insulin resistant, suffered only late failures or went into remission, often for longer than one year. The data bring us to the logical conclusion of IRD heterogeneity. Only some of these patients can benefit from temporary insulin therapy and the remission attempt should be limited to them.

Topics: Biomarkers; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Infusion Systems; Male; Middle Aged; Obesity; Prognosis; Prospective Studies; Treatment Outcome

In 38 diabetic patients, admitted on a long-term basis to a nursing home, the clinical situation and presence of secondary diabetic complications were assessed, and their macrovascular complications and degree of glycemic control compared with those in ambulatory diabetic patients, matched for age, sex, known duration of diabetes and specific antidiabetic therapy. No differences in blood glucose control, plasma triglycerides, blood pressure and serum creatinine were observed between both groups of patients. Plasma cholesterol levels were higher in the ambulatory patients (6.4 +/- 1.0 vs 5.6 +/- 1.1 mmol/l, P = 0.008). Twenty-two nursing home patients had suffered from stroke, against 4 ambulatory patients. Hypertension was found in almost 50% of all patients, whereas its prevalence was highest in the stroke patients (69 vs 36%, P less than 0.01). In the nursing home patients, peripheral vascular abnormalities, skin necrosis or leg ulcers and recurrent urinary tract infections were frequently encountered, whereas in the ambulatory patients cardiac complaints were more prevalent. Use of medication, especially diuretics and anticoagulant agents, was higher in the nursing home patients. Diabetes and the sequelae of its macrovascular complications may greatly impair the quality of life of the diabetic patient, and place a large financial and personal burden on the health care in general. Better identification of diabetic patients with a high risk of stroke is necessary.

Topics: Aged; Ambulatory Care; Blood Glucose; Blood Pressure; C-Peptide; Cerebrovascular Disorders; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Homes for the Aged; Humans; Hypertension; Hypoglycemic Agents; Insulin; Lipids; Long-Term Care; Male; Nursing Homes; Proteinuria

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Graft Survival; Humans; Kidney Transplantation; Middle Aged; Pancreas Transplantation; Survival Analysis; Time Factors; Uremia

We investigated the effect of chronic hyperglycemia on glucose transporters in erythrocytes of subjects with and without diabetes mellitus. We found a 22% increase in D-glucose-displaceable cytochalasin-B binding in erythrocyte membranes of diabetic subjects over those of controls (311 +/- 13 vs. 254 +/- 8 pmol/mg protein; P less than 0.001). This increased binding was due to a higher density of binding sites without a significant change in binding affinity. Cytochalasin-B binding to erythrocyte membrane correlated positively with both erythrocyte glycohemoglobin and serum glucose levels, but not with plasma C-peptide levels. The data are compatible with up-regulation of glucose transporters in the erythrocytes of subjects with chronic hyperglycemia. We suspect that this is brought about by increased synthesis and membrane incorporation of the glucose transporter during erythropoiesis.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Cytochalasin B; Diabetes Mellitus; Erythrocyte Membrane; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Monosaccharide Transport Proteins; Reference Values

Topics: Adult; Blood Proteins; C-Peptide; Cross Reactions; Diabetes Mellitus; Female; Humans; Hydrolysis; Male; Middle Aged; Radioimmunoassay; Sensitivity and Specificity; Time Factors

Topics: C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver; Liver Diseases

Fasting hyperglycemia in Type II (non-insulin-dependent) diabetes has been suggested to be due to hepatic overproduction of glucose and reduced glucose clearance. We studied 22 patients (10 lean and 12 obese) with newly diagnosed mild diabetes mellitus (fasting plasma glucose less than 15 mmol/l, urine ketone bodies less than 1 mmol/l), and two age- and weight-matched groups of non-diabetic control subjects. Glucose turnover rates and sensitivity to insulin were determined using adjusted primed-continuous [3-3H]glucose infusion and the hyperinsulinemic euglycemic clamp technique. Insulin-stimulated glucose utilization was reduced in both diabetic groups (lean patients: 313 +/- 35 vs 531 +/- 22 mg.m-2.min-1, p less than 0.01; obese patients: 311 +/- 28 vs 453 +/- 26 mg.m-2.min-1, p less than 0.01). Basal plasma glucose concentrations decreased 0.43 +/- 0.05 mmol/l per h (p less than 0.01). Glucose production rates were smaller than glucose utilization rates (lean patients: 87 +/- 3 vs 94 +/- 3 mg.m-2.min-1, p less than 0.01; obese patients: 79 +/- 5 vs 88 +/- 5 mg.m-2.min-1, p less than 0.01), were not correlated to basal glucose or insulin concentrations, and were not different from normal (lean controls: 87 +/- 4 mg.m-2.min-1; obese controls: 80 +/- 5 mg.m-2.min-1). These results suggest that the basal state in the diabetic patients is a compensated condition where glucose turnover rates are maintained near normal despite defects in insulin sensitivity.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Kinetics; Male; Middle Aged; Obesity

In 26 type 2 diabetic patients with failure to diet and sulphonylureas (fasting blood glucose levels greater than 8.0 mmol/l) the effects of insulin therapy on blood glucose control, islet B-cell function and plasma lipids were studied. Age was 58 +/- 11 (SD) yr, median duration of diabetes 6.5, range 1-24 yr, and body mass index 24.5, range 18.9-36.3 kg/m2. Six patients were obese. Therapy comprised twice daily injections of intermediate-acting insulin with additional fast-acting insulin when necessary. After six months, insulin dose was 39 +/- 10 U in the non-obese patients. Their fasting (14.0 +/- 2.7 mmol/l) and post-prandial blood glucose (17.9 +/- 4.5 mmol/l) and glycosylated haemoglobin (HbA1, 13.0 +/- 2.0%) declined to 7.7 +/- 1.6 mmol/l, 10.6 +/- 2.6 mmol/l and 9.5 +/- 1.0%, respectively (p less than 0.001). Median body weight increased by 3.7 kg (p less than 0.001). The changes in body weight correlated well with the changes in fasting blood glucose (r = -0.75, p less than 0.01) and HbA1 (r = -0.73, p less than 0.01). Fasting plasma insulin increased (p less than 0.01), whereas fasting plasma C-peptide and C-peptide release after glucagon did not change. Free fatty acids, LDL-cholesterol, total and VLDL-triglycerides showed a significant (p less than 0.05) decrease during insulin treatment. In the six obese patients insulin dose after six months was 44 +/- 18 U. Fasting blood glucose fell from 11.3 +/- 2.2 to 8.8 +/- 2.7 mmol/l (p less than 0.01), and HbA1 decreased from 10.7 +/- 1.1% to 9.8 +/- 1.3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipoproteins; Male; Middle Aged; Obesity; Sulfonylurea Compounds; Triglycerides

Insulinemia, concentration of C-peptide and glucagon in the blood was studied in chronic hepatitis patients showing moderate tolerance disorders to glucose and diabetes mellitus developed against the background of chronic pancreatitis. Both groups showed hyperglucagonemia. Basal hypoinsulinemia and reduction of the C-peptide level revealed only in patients suffering of chronic pancreatitis with secondary diabetes mellitus. Reduced reaction of beta-cells of the pancreas to physiologic stimulation by pancreosozymin were observed also in less significant disorders of tolerance to glucose. The authors discuss the significance of changes in the sequential development of different degrees of disorders of the carbohydrate metabolism in patients with chronic recurrent pancreatitis.

Topics: C-Peptide; Carbohydrate Metabolism; Cholecystokinin; Chronic Disease; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Pancreatitis; Recurrence

The insulin secretory capacity of three groups of Nigerian African diabetics was assessed by measuring the concentration of C-peptide before and after stimulation with oral glucose. Group 1 subjects had a history of keto-acidosis and were treated with insulin. Those in group 2 had no history of keto-acidosis but required insulin to normalize blood glucose while those in group 3 also had no history of keto-acidosis and were treated with diet alone or in combination with oral hypoglycaemic drugs. C-peptide levels (mean +/- s.e.m.) showed group 1 subjects to be insulin deficient (fasting 0.08 +/- 0.04 pmol/ml, peak 0.14 +/- 0.03 pmol/ml), group 2 to have reduced insulin secretion (fasting 0.16 +/- 0.01 pmol/ml, peak 0.35 +/- 0.01 pmol/ml) and group 3 to have a moderately reduced fasting insulin and a higher peak insulin secretion (fasting 0.27 +/- 0.03 pmol/ml, peak 1.49 +/- 0.4 pmol/ml) compared with a non-diabetic control group (fasting 0.30 +/- 0.03 pmol/ml, peak 1.16 +/- 0.1 pmol/ml). Although the aetiology of diabetes in the Nigerian African is unclear, a spectrum of the disease exists which is similar to that in Caucasian population.

Topics: Adult; Black People; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Fasting; Glucose; Humans; Insulin; Male; Middle Aged; Nigeria

Cases of malnutrition-related diabetes mellitus conforming to the description of the protein deficient pancreatic diabetes type in Ethiopian patients were compared with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic. Fourteen of 39 malnutrition-related diabetes mellitus patients had fat malabsorption compared with only two of ten Type 1 diabetic patients and one of nine control subjects. Xylose absorption was normal favouring a pancreatic cause for the malabsorption. Plasma C-peptide during oral glucose tolerance test was significantly lower than that in Type 2 diabetic patients and normal control subjects (p less than 0.01 to 0.001) and was also consistently but not significantly higher than in Type 1 diabetic patients. Glucagon secretion patterns were similar in malnutrition-related and Type 1 diabetic patients. Of 23 new malnutrition-related diabetic patients treated with glibenclamide after nutritional rehabilitation and insulin treatment, only three responded, 14 were unresponsive but remained ketosis free for over eight days while another six developed ketoacidosis or significant ketonuria within two to six days during the trial. Sixteen unselected Type 1 diabetic patients who discontinued their insulin therapy all developed frank ketoacidosis after a mean of 5.5 days. The similarity of the malnutrition-related and Type 1 diabetes mellitus in age of onset, insulin requirement for diabetic control and appearance of ketosis-proneness in some cases, together with the similarity of C-peptide and glucagon secretion patterns suggest that the protein deficient pancreatic diabetes variant of malnutrition-related diabetes mellitus may be Type 1 diabetes mellitus modified by the background of malnutrition rather than an aetiologically separate entity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Ethiopia; Female; Glucagon; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Protein-Energy Malnutrition; Reference Values

To determine the effects of short-term fasting on carbohydrate tolerance, 10 obese women with noninsulin-dependent diabetes mellitus (NIDDM) were studied with meal tolerance tests before and after 3 days of fasting. After 3 days' fast, basal serum glucose declined from 15.2 +/- 0.9 to 7.5 +/- 0.7 mmol/L (273 +/- 17 to 135 +/- 13 mg/dL) (mean +/- SEM, p less than 0.001) and the glycemic response to the test meal (area under the glucose curve) improved by 31%. There were no changes in basal or postprandial insulin levels but a slight increase in serum c-peptide. Resting metabolic rate and the thermic effect of food were unchanged. There was a slight but insignificant change in basal and postprandial free fatty acid levels and a significant elevation of basal beta-hydroxybutyrate levels. Blood lactate rose significantly (from 0.9 to 2.0 mM) during the initial meal tolerance test, but no rise in lactate was seen in the meal tolerance test after fasting. Two subgroups of patients were identified based on the degree of glycemic improvement after short-term fasting. Those with lesser improvement in serum glucose showed overnight rises in serum glucose during the period of fasting (the dawn phenomenon), while those patients who normalized serum glucose showed a steady fall in serum glucose. This finding may help to predict the glycemic response to long-term calorie restriction. Carbohydrate tolerance improves in obese diabetic (NIDDM) women after 3 days of fasting, in contrast to the impairment of glucose tolerance seen in lean or obese nondiabetic subjects after fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Energy Metabolism; Fasting; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Hydroxybutyrates; Insulin; Lactates; Middle Aged; Obesity; Research Design; Time Factors

Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insu

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Models, Theoretical; Obesity; Weight Loss

beta-Cell function (plasma C-peptide) in 17 fibrocalculous pancreatic diabetic (FCPD) subjects (14 newly diagnosed) was not different at presentation from that in 14 matched insulin-dependent diabetic subjects. After insulin treatment and improvement in the patients' nutritional and metabolic status, fasting and postglucose plasma C-peptide concentrations showed a significant increase (fasting 0.06 +/- 0.01 to 0.17 +/- 0.03 nM, peak 0.11 +/- 0.02 to 0.29 +/- 0.06 nM, mean +/- SE; P less than 0.01 for both). Thus, severely diminished beta-cell function in FCPD is partially reversible after treatment. This could contribute to the clinical metabolic peculiarities of this group of patients.

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Fibrosis; Follow-Up Studies; Fructose; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Male; Pancreatic Diseases

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus; Diagnosis, Differential; Glucagon; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Radioimmunoassay; Specimen Handling

Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non-diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous-pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components.

Topics: Adult; Blood Glucose; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; India; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Trypsin

A prospective study of 27 patients with diabetes mellitus was done to assess their basal and glucagon stimulated C-peptide levels. Based on recommended cut off values for both basal and stimulated C-peptide levels, these patients were subsequently classified as insulin or non-insulin requiring diabetics. As in most other studies, we demonstrated a good correlation between the basal and glucagon stimulated C-peptide levels. Of the 8 patients on insulin therapy prior to this test, we found that only 2 actually required insulin i.e. had poor pancreatic reserve. Of the remaining 19 patients who were on diet and/or oral hypoglycaemic agents, we found that only one newly diagnosed diabetic had a definitive indication for insulin therapy. Among the other diabetics with poor control despite being on oral hypoglycaemic therapy, we found they had good islet cell secretory capacity for insulin.

Topics: Administration, Oral; Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Time Factors

Epidermal and platelet-derived growth factors are potent mitogens for many types of cells, including smooth muscle cells. Epidermal growth factor in blood of humans is present both in platelets (as reflected in its serum level) and in plasma, the source(s) of which remains unknown. We assayed its level in 82 diabetic patients and 53 age-matched controls. In diabetes, epidermal growth factor level was increased in serum (191 +/- 43 vs 155 +/- 64 pmol/l, p = 0.0002) and plasma (53 +/- 9 vs 38 +/- 14 pmol/l, p less than 0.0001), without any difference between the patients with and without complications. Platelet-derived growth factor level was assayed only in serum of 19 patients with uncomplicated diabetes and found elevated (222 +/- 47) as compared with 13 controls (160 +/- 26 pmol/l), (p = 0.0002). Type of diabetes, its duration, mode of therapy, control, presence of retinopathy or albuminuria (in case of epidermal growth factor), as well as C-peptide age and sex did not correlate with epidermal or platelet-derived growth factor levels. Serum but not plasma epidermal and platelet-derived growth factor were negatively correlated with serum creatinine (correspondingly, r = -0.373, p = 0.0008 and r = -0.564, p = 0.0285). It is concluded that diabetes itself and not its complications cause increased levels of epidermal growth factor in plasma and serum and of platelet-derived growth factor in serum.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Epidermal Growth Factor; Female; Humans; In Vitro Techniques; Male; Middle Aged; Platelet-Derived Growth Factor; Radioimmunoassay; Regression Analysis

The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230,000 inhabitants), corresponding to an incidence rate of 53.100,000(-1).year-1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n = 233) after a median time of 31 (range 1-49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p less than 0.001), higher HbA1c (p less than 0.004), and lower C-peptide (p less than 0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.

Topics: Adolescent; Adult; Age Factors; Aged; Autoantibodies; Biomarkers; C-Peptide; Child; Diabetes Mellitus; Diet, Diabetic; Fasting; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Middle Aged; Prognosis; Sweden

To analyze the mechanisms of fasting-induced glucose intolerance, glucose metabolism was studied before and after the ingestion of 75 g glucose in 24 normal subjects fasted for either 14 h (n = 12) or 4 days (n = 12). The techniques included intravenous infusion of [6-3H]glucose and oral administration of [1-14C]glucose combined with indirect calorimetry. Compared with the controls, the starved subjects exhibited the following differences in glucose metabolism during the 5 h after glucose ingestion. 1) Mean incremental levels were fourfold higher for glucose and 40% higher for insulin. 2) Absorption of oral glucose was delayed and prolonged, but total amount reaching systemic circulation in 5 h was identical in the two groups (approximately 63 g). 3) Suppression of hepatic glucose output was reduced (-12 +/- 1 vs. -22 +/- 2 g). 4) Consequently, the increment in peripheral appearance of total glucose (exogenous plus endogenous) was augmented (+ 52 +/- 2 vs. +41 +/- 2 g). 5) Mean glucose clearance increased significantly less (+28 +/- 7 vs. +96 +/- 10 ml/min). 6) Oxidation of oral glucose was reduced (9 +/- 2 vs. 36 +/- 3 g), and nonoxidative disposal (presumably storage) was enhanced (56 +/- 2 vs. 36 +/- 3 g) in the presence of an elevated fat oxidation (35 +/- 2 vs. 22 +/- 4 g). Thus the alterations in glucose homeostasis responsible for the starvation-induced glucose intolerance are located both at the splanchnic (hepatic) and peripheral levels.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Fatty Acids, Nonesterified; Glucagon; Humans; Hydroxybutyrates; Insulin; Lactates; Male; Starvation

The effect of fasting during the holy month of Ramadan on the metabolic control of 39 patients with overweight and non-insulin-dependent diabetes (NIDD) was studied. There were 29 females and 10 males with a mean age of 51.5 +/- 1.65 years and body mass index of 31.5 +/- 0.98 kg/m2. All were treated with diet and oral hypoglycaemic agents (OHA). There was no change in body weight, fasting plasma glucose, glycosylated haemoglobin (HbA1), C-peptide and insulin blood levels at the end of fasting. Total blood cholesterol concentration rose significantly (p 0.05) but not triglycerides at the end of Ramadan. There were no acute metabolic complications (e.g. hypoglycaemia) in the present study. We conclude that fasting during Ramadan is generally safe in NIDD. However, patients should be advised to make use of this opportunity to combine the spiritual benefit with improvement in the metabolic control of the diabetes mainly through weight reduction.

Topics: Adult; Aged; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Islam; Male; Middle Aged; Obesity; Patient Compliance; Prospective Studies; Triglycerides

In high degree obesity there a significantly smaller area under the curve of C-peptide after stimulation with Tolbutamide and significantly lower insulin sensitivity measured in vivo by euglycemic hyperinsulinemic clamp-technique (Biostator) than in moderate obesity. This allows the conclusion that high degree obesity is a risk factor for the development of diabetes mellitus.

Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity; Risk Factors; Tolbutamide

Ninety-eight patients with diabetes mellitus (52 women and 46 men) underwent a glucagon stimulated C-peptide test. Treatment was instigated on the basis of classical criteria, independent of the test results, and remained unchanged during a 2-yr test period. The type of treatment and metabolic control were then related to the test results. Fasting C-peptide concentrations do not discriminate between insulin dependent and non-insulin dependent diabetes mellitus. C-peptide concentrations 10 min after intravenous injection of 1 mg of glucagon, however, correctly classified the patients. With the help of this test, the correct model of treatment for patients with diabetes mellitus can be chosen.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged

Diabetes mellitus is a major health problem in Saudi Arabia. The evaluation of endogenous insulin secretion at diagnosis has not yet been studied in this population. We have therefore studied fasting and post-glucagon stimulation levels of glucose, insulin and C-peptide in 216 newly diagnosed untreated diabetic patients. The mean +/- SD fasting insulin and C-peptide levels were 14.0 +/- 1.8 microU/ml and 1.8 +/- 0.4 ng/ml, while post-glucagon stimulation levels were 21.1 +/- 3 microU/ml and 2.4 +/- 0.4 ng/ml. There were significant post-stimulatory increment levels for insulin, from 4.9 to 13.7 microU/ml, and C-peptide from 0.2 to 1.3 ng/ml (P less than 0.001). Such increments did not affect specified age distribution. We found a significant correlation between the fasting levels and post-stimulation levels of C-peptide and insulin. Obesity correlated with higher basal and post-stimulation levels of both hormones (r = 0.67, P less than 0.001). The mean +/- SD fasting insulin and C-peptide levels were 18.5 +/- 9.1 microU/ml and 2.4 +/- 0.8 ng/ml for obese patients and 11.5 +/- 5.1 microU/ml and 1.9 +/- 1.1 ng/ml for non-obese patients. The type of diabetes among the Saudi adult diabetic patients studied is characterized by high basal C-peptide and insulin levels which increase significantly with stimulation, suggesting diminished but present endogenous B-cell function.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Fasting; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Saudi Arabia

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance,

Topics: Blood Glucose; C-Peptide; Carbon Dioxide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Eating; Female; Glucagon; Glucose; Humans; Insulin; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Middle Aged; Obesity

The aim of this study was to assess the possible relationship between high density lipoprotein cholesterol (HDL-C) concentrations and endogenous insulin secretion, as measured by basal serum C-peptide secretion. Eighty-nine non-insulin-dependent diabetic patients (NIDDs) being treated with sulfonylureas were studied. There were 47 men and 42 women matched for age, body mass index (BMI), duration of diabetes and glycemic control. Blood samples were taken after an overnight fast. HDL-C concentrations were significantly lower in males (45.9 +/- 11.2 mg/dl) than in females (52.9 +/- 13.1 mg/dl) (p less than 0.01). There was a negative correlation between C-peptide and HDL-C (males r = -0.40, p less than 0.01; females r = -0.42, p less than 0.01), and a positive correlation between C-peptide and serum triglyceride (Tg) (males r = +0.36, p less than 0.05; females r = +0.31, p less than 0.05).

Topics: Aged; Blood Glucose; C-Peptide; Cholesterol, HDL; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Osmolar Concentration; Sex Characteristics; Sulfonylurea Compounds; Triglycerides

24-h urinary C-peptide excretion was studied in 119 women with gestational diabetes before and after treatment with diet or diet and insulin. The 24-h urinary C-peptide excretion in normal-weight gestational diabetic women at diagnosis was also compared to that of a healthy reference group. There was a wide variation in urinary C-peptide values which tended to be higher in normal-weight women with gestational diabetes at diagnosis compared to the reference group, but it did not reach statistical significance. Post partum gestational diabetic women had significantly higher urinary C-peptide excretion (p less than 0.002) than the reference group, indicating insulin resistance in women with gestational diabetes at this time. In 29 overweight women with gestational diabetes 24-h urinary C-peptide excretion did not significantly differ from that in normal-weight women with gestational diabetes. In 32 women with a more marked deviation in glucose tolerance (area greater than or equal to 46 mmol/l) 24-h urinary C-peptide values were significantly (p less than 0.05) higher than in 58 women with gestational diabetes with an area between 42 and 45.9 mmol/l. Both treatment alternatives, diet and diet plus insulin, significantly reduced postprandial blood glucose values (p less than 0.05) and urinary C-peptide excretion was significantly decreased (p less than 0.05).

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet, Diabetic; Female; Humans; Insulin; Obesity; Pregnancy; Pregnancy in Diabetics; Reference Values

Pancreatic beta cell function was measured in 15 nondiabetic controls, 10 insulin-dependent diabetics (IDD) and 19 non-insulin-dependent diabetics (NIDD), aged 18 to 45 years, by means of the peripheral serum C-peptide response to 1 mg of glucagon. The fasting serum C-peptide (FCP) in IDD was lower than in the controls and NIDD (p less than 0.01), but there was no significant difference between the controls and NIDD (p greater than 0.05). The maximal in crement of serum C-peptide (delta CP) after glucagon stimulation in the controls was higher than in IDD and NIDD (p less than 0.01), and there was a gap between IDD (less than or equal to 0.69 ng/ml) and NIDD (1.20 ng/ml). During the glucagon test, serum C-peptide concentrations were highest in the first 15 minutes unlike plasma glucose which reached its highest value between 20 and 40 minutes. NIDD, either obese or nonobese, had a lower mean delta CP value than did controls. In the controls, IDD and NIDD, the FCP was correlated well with delta CP (r = 0.61, 0.93 and 0.59) but not with fasting plasma glucose (r = 0.19, -0.08 and 0.23). During the glucagon test, the mean maximal increments of plasma glucose were between 52.5 and 62.5 mg/dl. Nausea was the main complaint in 19 (43%) of the subjects but it was mild and transient. In conclusion, measuring serum C-peptide response after glucagon stimulation is a simple and safe test which may be a discriminative method to establish insulin dependency in young diabetic patients.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged

It has been shown that before insulin treatment children with diabetes mellitus diagnosed for the first time manifested heterogenous endogenous secretion of insulin, which did not correlate with the disease standing before diagnosis establishment.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Male

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Humans; Insulin; Male; Middle Aged; Obesity

In chronic pancreatitis with moderate derangements of carbohydrate tolerance (detected by the double glucose test), the basal concentrations of insulin and C-peptide in blood are normal whereas in patients with secondary diabetes mellitus are lowered. Glucagonemia is increased in patients of both groups. Euphylline (applied as an inhibitor of nucleotide phosphodiesterase), calcium gluconate and the adrenomimetic drug isadrin consistently increased insulinemia and the blood level of C-peptide in patients with chronic pancreatitis both with moderate and appreciable derangements of glucose tolerance. In patients with secondary diabetes that developed in the presence of pancreatitis, these drugs did not influence glucagonemia. The clinical prospects of the making use of the stimulating action of euphylline, calcium gluconate and isadrin on the function of beta-cells of the pancreas in chronic pancreatitis patients are under discussion.

Topics: Aminophylline; C-Peptide; Calcium Gluconate; Chronic Disease; Diabetes Mellitus; Glucagon; Gluconates; Glucose Tolerance Test; Humans; Insulin; Isoproterenol; Pancreas; Pancreatitis; Recurrence

Sixty-one patients with non-insulin-dependent diabetes mellitus and fasting blood glucose of 12.0 +/- 0.6 mmol/l were studied before and after dietary treatment in an outpatient setting. At the start of the study 33 patients were obese (body mass index greater than 27.0 kg/m2). Twenty patients were newly diagnosed, median known duration of diabetes in the others was 5 years. Beta-cell function was measured by the release of C-peptide after i.v. injection of 1 mg glucagon (area under the curve of C-peptide = AUC-cp), as well as calculated according to the formulae of Matthews. Insulin action was estimated by measurement of fasting blood glucose, insulin and free fatty acids (FFA) concentrations. Non-obese patients showed more severe beta-cell deficiency than the obese ones (AUC-cp 2586 +/- 158 vs. 3294 +/- 277 pmol/l per 15 min), and did not improve in metabolic control during treatment. In the obese patients three response patterns to treatment were observed: weight loss and improvement in metabolic control accompanied primarily with increased beta-cell function or increased insulin action, or worsening of metabolic control. Those with less impaired beta-cell function and shorter known duration of diabetes showed the most favourable response.. non-obese type 2 diabetes patients with fasting glucose levels above 10 mmol/l do not improve on dietary treatment alone; in obese type 2 diabetics weight reduction is essential and results in metabolic improvement, irrespective of the preceding fasting blood glucose concentrations. Improved beta-cell function as well as increased insulin action are responsible for this improvement.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Weight Loss

Topics: Adolescent; Adult; Aged; Amylases; C-Peptide; Calcinosis; Developing Countries; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Japan; Male; Manihot; Middle Aged; Pancreas; Pancreatic Diseases; Protein Deficiency

The influence of combined therapy using insulin and oral hypoglycaemic agents on blood glucose control and on insulin secretion in Type 2 diabetic patients with secondary failure to oral hypoglycaemic agents was evaluated. Type 2 diabetic patients (n = 180) (98 normal-weight, 82 over-weight), at least 3 years from diagnosis, and having poor blood glucose control on oral hypoglycaemic agents for at least 3 months (fasting plasma glucose greater than 10.0 mmol l-1) despite intensive efforts at improvement, were included in the study. A single daily insulin injection (human ultralente), at a dose of 0.22 +/- 0.07 U kg-1 d-1 in normal-weight and 0.33 +/- 0.10 U kg-1 d-1 in over-weight patients, was added to the previous dietary and drug treatment for 6 months. A progressive and significant (2p less than 0.001) reduction of the mean daily blood glucose was observed during the first 3 months of combined therapy (from 13.2 +/- 3.2 to 8.1 +/- 2.1 mmol l-1 in normal-weight and from 13.4 +/- 3.1 to 8.8 +/- 2.3 mmol l-1 in over-weight patients), with no further significant changes thereafter. A significant increase (2p less than 0.001) in the mean daily C-peptide concentration (from 0.50 +/- 0.30 to 0.71 +/- 0.29 nmol l-1 in normal-weight and from 0.78 +/- 0.36 to 1.00 +/- 0.41 nmol l-1 in over-weight patients) took place during combined therapy. No changes of body weight (+ 1.5 +/- 1.2 kg in normal-weight and + 1.0 +/- 1.0 kg in over-weight patients) were observed.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Eating; Fasting; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin, Long-Acting; Obesity; Recombinant Proteins

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Antibodies; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Pancreatic Diseases; Prospective Studies; Uganda

Topics: Administration, Oral; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Humans; Insulin; Male; Middle Aged; Tanzania

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Male; Obesity

Previous studies demonstrated that administration of insulin and oral hypoglycemic agents tends to produce weight gain in type II diabetic patients. The goal of this study was to determine the potential contribution of changes in metabolic rate and urinary glucose excretion to changes in energy balance associated with treatment with glyburide and insulin. Six obese type II diabetic patients (52-61 yr old; 123-214% of ideal weight) were fed a weight-maintaining diet of fixed composition and caloric content in a Clinical Research Center. The mean fasting plasma glucose concentrations were 10.7 +/- 1.3 (+/- SE) mmol/L before treatment, 7.9 +/- 1.4 mmol/L at the end of 2 weeks of glyburide treatment, and 5.2 +/- 0.3 mmol/L at the end of 2 weeks of insulin treatment. Urinary glucose excretion decreased from 48 +/- 19 g/day before treatment to 20 +/- 9 g/day at the end of glyburide treatment and 2 +/- 1 g/day at the end of insulin treatment. Neither treatment affected mean postabsorptive resting metabolic rate (untreated 4.86 +/- 0.50 kJ/min; glyburide-treated, 4.63 +/- 0.45 kJ/min; insulin-treated, 4.70 +/- 0.46 kJ/min) or postprandial resting metabolic rate (untreated, 5.71 +/- 0.55 kJ/min; glyburide-treated, 5.60 +/- 0.39 kJ/min; insulin-treated, 5.70 +/- 0.51 kJ/min). However, the two patients with the largest decreases in urinary glucose excretion also had decreases in energy expenditure. These data indicate that many obese type II diabetic patients could have significant weight gain from reduced energy losses alone.

Topics: Blood Glucose; Blood Urea Nitrogen; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Epinephrine; Female; Glucagon; Glyburide; Glycosuria; Humans; Insulin; Male; Middle Aged; Norepinephrine; Obesity

In order to evaluate whether the hypoglycaemic action of glibenclamide during chronic treatment of obese subjects with NIDDM is primarily due to changes in the daytime insulin level, in insulin secretion or to changes in tissue sensitivity to insulin, we studied eight NIDD's (age 43 +/- 3 years, body mass index 31.4 +/- 2.6 kg/m2) inappropriately controlled by dietary treatment alone. Before and after three months of glibenclamide treatment, plasma glucose, insulin and C-peptide were measured hourly (0800 to 1600 hours) and in vivo insulin sensitivity was evaluated using the sequential euglycaemic clamp (insulin infusion: 0, 0.8, 3.2 mU/kg/min) in combination with 3-3H-glucose tracer technique. During glibenclamide treatment the mean daytime glucose level was reduced (11.2 +/- 0.5 versus 7.1 +/- 0.4 mmol/l, p less than 0.001) but not to normal (5.2 +/- 0.2 mmol/l, p less than 0.001). Before treatment the mean daytime insulin level was higher than normal (38 +/- 58 versus 24 +/- 2 microU/ml, p less than 0.05) and was increased by 79% (67 +/- 8 microU/ml, p less than 0.001) after three months of treatment. In contrast the mean C-peptide level was unchanged (1.40 +/- 0.13 versus 1.30 +/- 0.17 nmol/l, p = NS), although it was higher than normal on both occasions (0.84 +/- 0.09 nmol/l, p less than 0.05). The basal hepatic glucose production rate was normal before treatment (86 +/- 4 versus 82 +/- 3 mg.m-2.min-1 in normals, p = NS), and unchanged after glibenclamide treatment (80 +/- 3 mg.m-2.min-1, p = NS versus pretreatment level).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Insulin; Male; Obesity; Reference Values

We assessed the effects of weight loss on pancreatic secretion and hepatic extraction of insulin in 11 obese subjects with noninsulin-dependent diabetes mellitus. Weight loss of 15.4 +/- 2.0 kg (mean +/- SE) resulted in decreased fasting insulin [20.2 +/- 2.5 to 9.8 +/- 2.5 microU/mL (145 +/- 18 to 70 +/- 18 pmol/L); P less than 0.02] and C-peptide (850 +/- 80 to 630 +/- 110 pmol/L; P less than 0.05) levels. The plasma glucose response to oral glucose and iv glucagon was improved with unchanged peripheral insulin levels. When plasma glucose levels were matched to those before weight loss, peripheral serum insulin and plasma C-peptide responses to iv glucagon were increased and similar to those in obese nondiabetic subjects studied at euglycemia. The total insulin response (area under the curve) to iv glucagon was reduced 30% (P less than 0.005), while the total C-peptide response area did not change after weight loss. At matched hyperglycemia, the total response area was enhanced 72% for insulin (P less than 0.002) and 64% for C-peptide (P less than 0.001). Incremental (above basal) response areas after weight loss did not change for insulin, but increased 66% for C-peptide (P less than 0.05). The incremental areas were augmented nearly 2-fold (196%) for insulin (P less than 0.01) and 1.7-fold (173%) for C-peptide (P less than 0.01) when assessed at matched hyperglycemia. Both basal (7.3 +/- 0.5 to 14.1 +/- 1.8; P less than 0.01) and total stimulated (6.1 +/- 0.4 to 8.8 +/- 1.4; P less than 0.05) C-peptide to insulin molar ratios increased after weight loss. We conclude that after weight loss in noninsulin-dependent diabetes mellitus, 1) insulin secretion is decreased in the basal state but increased after stimulation; 2) changes in insulin secretion are reflected by peripheral levels of C-peptide but not insulin, due in part to enhanced hepatic insulin extraction; and 3) at matched levels of hyperglycemia insulin secretion is markedly increased and similar to that in obese nondiabetic subjects studied at euglycemia.

Topics: Basal Metabolism; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Fasting; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver; Male; Middle Aged; Obesity; Pancreas

Topics: C-Peptide; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Sulfonylurea Compounds

Glucose cycling (GC; G in equilibrium G6P) equals 14% of glucose production in postabsorptive man. Our aim was to determine glucose cycling in six lean and six overweight mild type II diabetics (fasting glycemia: 139 +/- 10 and 152 +/- 7 mg/dl), in postabsorptive state (PA) and during glucose infusion (2 mg/kg per min). 14 control subjects were weight and age matched. GC is a function of the enzyme that catalyzes the reaction opposite the net flux and is the difference between hepatic total glucose output (HTGO) (2-[3H]glucose) and hepatic glucose production (HGP) (6-[3H]-glucose). Postabsorptively, GC is a function of glucokinase. With glucose infusion the flux is reversed (net glucose uptake), and GC is a function of glucose 6-phosphatase. In PA, GC was increased by 100% in lean (from 0.25 +/- 0.07 to 0.43 +/- .08 mg/kg per min) and obese (from 0.22 +/- 0.05 to 0.50 +/- 0.07) diabetics. HGP and HTGO increased in lean and obese diabetics by 41 and 33%. Glucose infusion suppressed apparent phosphatase activity and gluconeogenesis much less in diabetics than controls, resulting in marked enhancement (400%) in HTGO and HGP, GC remained increased by 100%. Although the absolute responses of C-peptide and insulin were comparable to those of control subjects, they were inappropriate for hyperglycemia. Peripheral insulin resistance relates to decreased metabolic glucose clearance (MCR) and inadequate increase of uptake during glucose infusion. We conclude that increases in HGP and HTGO and a decrease of MCR are characteristic features of mild type II diabetes and are more pronounced during glucose infusion. There is also an increase in hepatic GC, a stopgap that controls changes from glucose production to uptake. Postabsorptively, this limits the increase of HGP and glycemia. In contrast, during glucose infusion, increased GC decreases hepatic glucose uptake and thus contributes to hyperglycemia. Obesity per se did not affect GC. An increase in glucose cycling and turnover indicate hepatic insulin resistance that is observed in addition to peripheral resistance. It is hypothesized that in pathogenesis of type II diabetes, augmented activity of glucose-6-phosphatase and kinase may be of importance.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose; Humans; Infusions, Intravenous; Insulin; Liver; Male; Middle Aged; Obesity

It is generally assumed that diet therapy can ameliorate the metabolic derangements experienced by obese type 2 diabetic patients, thereby leading to discontinuation of insulin or oral sulfonylurea drug therapy. We decided to retrospectively investigate which clinical and biochemical parameters affect therapeutic responses.. Sixty-four poorly controlled obese diabetic patients were hospitalized and placed on a precisely defined, hypocaloric diet. Known duration of diabetes, type of pharmacologic therapy, body weight, weight loss, fasting plasma glucose concentrations, C-peptide levels, hemoglobin A1C, and plasma lipid levels were assessed, as were nitrogen and electrolyte balances.. Average weight loss was 13 pounds in a mean of 23 days. During hospitalization, the mean fasting plasma glucose value for the group fell from 221 +/- 10 to 122 +/- 5 mg/dl. In 45 patients (73 percent), the final fasting plasma glucose level was less than 125 mg/dl (mean: 102 +/- 2 mg/dl). Oral glucose tolerance even in those patients in whom fasting plasma glucose levels normalized was still grossly diabetic at the end of the hospital stay, deteriorating further after three days of liberalized caloric intake. In part this may have been due to decreased insulin secretory reserve as reflected by blunted plasma C-peptide response. Forty of 42 patients who entered the study taking insulin were able to discontinue the drug within one to seven days of hospitalization. After a mean follow-up period of 19 months, only 10 of 50 patients continued to maintain fasting euglycemia; five were on diet alone, and five were receiving oral hypoglycemic agents. Thirteen patients were receiving insulin therapy.. Diet therapy in these patients resulted in short-term improvement of glycemic control and, in the majority, normalization of fasting plasma glucose levels. However, long-term outpatient follow-up revealed that relapse occurred in most patients.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Middle Aged; Obesity; Retrospective Studies; Time Factors

The purpose of the present study was to elucidate the interrelationship between pancreatic polypeptide (PP) and other pancreatic endocrine hormones. For this purpose, a radioimmunoassay (RIA) system of plasma PP was established and the changes in plasma PP, plasma immunoreactive insulin (IRI), plasma C-peptide reactivity (CPR) and plasma immunoreactive glucagon (IRG) following oral administration of glucose were examined in ten normal subjects and twenty-five patients with liver cirrhosis. Patients with liver cirrhosis were classified into a normal glucose tolerance group (NGT), an impaired glucose tolerance group (IGT), and a diabetes mellitus group (DM) on the basis of the glucose tolerance curves obtained after the oral administration of glucose. In the IGT and DM groups, fasting plasma PP levels were significantly elevated when compared with those in the control and NGT groups. Also oral administration of 75g glucose elicited an exaggerated rise in plasma PP in the IGT and DM groups when compared with the response in the control and NGT groups. On the other hand, PP response to glucose in the NGT group was similar to that in the control group. Plasma IRI increased markedly before and after oral administration of glucose in the IGT and DM groups when compared with the control groups. In these patients, plasma levels of CPR almost paralleled those of IRI. No significant difference was noted between the NGT group and the control group with regard to plasma IRI and CPR levels before and after oral glucose loading. Accordingly, insufficient insulin action was considered to exist in the IGT and DM groups. This insufficiency in insulin action was expressed in terms of the indices of increase in plasma IRI and CPR, delta IRI/delta BS and delta CPR/delta BS, which corresponded to the elevated blood glucose levels, being significantly lower in the IGT and DM groups than in the control and NGT groups 30 minutes after oral administration of glucose. No significant difference was noticeable between the NGT group and control group with regard to these indices. In the patients with liver cirrhosis, the delta PP value, obtained by subtracting the plasma PP level during fasting from the PP level 30 minutes after oral glucose loading, was inversely correlated with the values of both delta IRI/delta BS and delta CPR/delta BS.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: C-Peptide; Diabetes Complications; Diabetes Mellitus; Glucagon; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Liver Cirrhosis; Middle Aged; Pancreatic Hormones; Pancreatic Polypeptide; Radioimmunoassay

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Diltiazem; Double-Blind Method; Electrocardiography; Female; Glucose Tolerance Test; Humans; Obesity; Risk Factors

We measured fructosamine concentrations in nonfasted serum from 7094 residents (82.8% of the estimated population) of Kawerau, New Zealand, including 65 known diabetic patients (prevalence of 0.92%). Fructosamine results showed a trimodal frequency distribution, with cutting points corresponding to 5th and 95th percentile values. Forty-two diabetic individuals had levels that exceeded the 95th percentile. These individuals had more severe metabolic abnormalities, characterized by lower plasma C-peptide and elevated fasting plasma glucose concentrations. Mean fructosamine values also showed a significant increase with age and a highly significant age-ethnic interaction that paralleled the higher frequency of diabetes in older age groups and among elderly Maori people. However, as a screening method in the general population, fructosamine measurement was diagnostically deficient because of a weak correlation with serum albumin. Arithmetic correction for albumin concentration in the sample did not increase the diagnostic usefulness of the test.

Topics: Adult; Age Factors; Blood Glucose; C-Peptide; Diabetes Mellitus; Ethnicity; Europe; Female; Fructosamine; Hexosamines; Humans; Male; Middle Aged; New Zealand; Serum Albumin; White People

The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes.

Topics: Adult; Age Factors; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Obesity; Pedigree; Sex Factors

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; HLA Antigens; Humans; Remission, Spontaneous

Topics: Adolescent; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Injections, Intravenous; Islets of Langerhans

The aim of this study was to evaluate whether the correlation between insulin resistance and peripheral hyperinsulinaemia existing in mild glucose intolerance corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the possibility that insulin resistance is related to insulin metabolism was examined. Twenty five subjects with fasting normoglycaemia and an abnormal glucose response to the oral glucose tolerance test (OGTT) were studied. Insulin secretion by the pancreas was estimated by means of fasting C-peptide levels in peripheral blood. Insulin resistance was estimated by the rate of glucose disappearance from plasma after i.v. insulin injection. Insulin metabolism was estimated indirectly by the C-peptide: insulin molar ratio. A negative correlation was found between the glucose disappearance rate from plasma after i.v. insulin injection and fasting insulin levels (r = -0.677, p less than 0.001), but not fasting C-peptide concentrations (r = -0.164, p = NS). Glucose disappearance rate from plasma correlated positively with the C-peptide: insulin molar ratio (r = 0.626, p less than 0.001). These results suggest that in mild glucose intolerance insulin resistance and insulin secretion by the pancreas are not related phenomena, and that the defect responsible for insulin resistance might also be implicated in the impaired insulin metabolism.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Metabolic Clearance Rate; Middle Aged

In a 3 yr epidemiological cohort study of 273 diabetics treated with oral hypoglycaemic agents (OHA) and 60 diet-treated diabetics the predictive value of fasting plasma C-peptide levels was assessed with the attempt to discriminate between insulin dependence and non-insulin dependence. Serum insulin, blood glucose, haemoglobin AI, bicarbonate, urine for ketone bodies, height and weight were measured too. All but 8 OHA-treated patients (97%) had fasting C-peptide greater than 0.40 pmol/ml at both investigations. Six had C-peptide in the interval 0.21-0.40 pmol/ml at both investigations and 2 a C-peptide less than or equal to 0.20 pmol/ml all of which became insulin dependent during the 3 yr period. The highest fasting C-peptide concentrations were found in overweight diabetics with a blood glucose level greater than 8.5 mmol/l. Overweight diabetics had significantly elevated fasting insulin compared to the normal weights but when the IRI concentrations were corrected by the body mass index hyperinsulinaemia was positively correlated with high levels of blood glucose and haemoglobin AI, i.e. poor glycaemic control and not with overweight. The results suggest that determination of fasting plasma C-peptide can be an additional clinical help in discriminating between insulin dependence and non-dependence.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diet, Diabetic; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Middle Aged

Serum lipids and lipoproteins were studied in 149 non-insulin-dependent diabetic subjects treated with diet or oral drugs (75 men, 74 women) and in 101 nondiabetic control subjects (49 men, 52 women) in relation to endogenous insulin secretion capacity measured by plasma C-peptide response to intravenous glucagon. Serum HDL- and HDL2-cholesterol concentrations were lower and VLDL-cholesterol and total and VLDL-triglyceride concentrations higher in subjects with high C-peptide response (above the median) than in subjects with low C-peptide response (lower or equal to median) both in diabetic and control subjects of both sexes. Adjustment for the effect of obesity abolished these differences in serum lipids and lipoproteins in diabetic subjects but not in control subjects. This may indicate that obesity has stronger influence on serum lipids in diabetic subjects than in nondiabetic subjects.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucagon; Humans; Insulin; Insulin Secretion; Lipids; Lipoproteins; Male; Middle Aged; Obesity

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreatitis

A soluble-phase proinsulin assay has been developed which does not require solid-phase antibody-binding. A human proinsulin standard curve is prepared in insulin-free and proinsulin-free plasma for comparison with unknown plasma samples. Proinsulin and insulin are bound with excess anti-insulin antiserum, and free C-peptide is removed by charcoal adsorption. The supernatant is then assayed using a routine C-peptide radioimmunoassay which utilises anti-C-peptide antiserum. The sensitivity of the assay (2 standard deviations above zero) is 9 pmol/L using 200 microL plasma sample. The assay is free from insulin cross-reactivity up to 100 mU/L and C-peptide up to 2000 pmol/L. Between-assay CV is 13% at 100 pmol/L. The assay has been used in subjects with hypoglycaemia of various aetiologies and has shown that a raised plasma proinsulin in the presence of hypoglycaemia can occur in sulphonylurea-induced and reactive hypoglycaemia as well as in insulinomas. After hyperglycaemic clamps at 7.5, 10 and 15 mmol/L glucose, type II diabetics both on and off sulphonylurea, were found to have lower proinsulin concentrations compared with normal subjects, commensurate with the diabetics' lower insulin responses.

Topics: Adult; Antibody Specificity; C-Peptide; Diabetes Mellitus; Female; Humans; Hypoglycemia; Immune Sera; Insulin; Male; Proinsulin; Radioimmunoassay; Reference Standards

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Food; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male

Immunoreactive C-peptide was evaluated in the plasma and pancreas of Aston ob/ob and C57BL/KsJ db/db mice in relation to disturbances in pancreatic B-cell function. At 18-24 weeks of age, ob/ob and db/db mice displayed hyperglycaemia (1.6 and 3.8 fold increases respectively) and hyperinsulinaemia (10.8 and 5.1 fold increases respectively) despite a similar pancreatic insulin content to their respective non-diabetic lean control mice. Immunoreactive C-peptide concentrations in the plasma and pancreas of the mutants corresponded with the degree of hyperinsulinaemia and pancreatic insulin content, and the insulin: C-peptide molar ratios in both mutants were similar to lean controls. In ob/ob mice parenteral glucose administration decreased plasma insulin and C-peptide concentrations, despite markedly raised glucose concentrations. However, administration of a low dose of insulin (5 U/kg) to lean mice and much higher doses of insulin (50 and 120 U/kg) to ob/ob mice markedly decreased plasma glucose and C-peptide concentrations. When the rate and extent of insulin-induced glucose suppression observed in ob/ob mice was mimicked in lean mice, an almost complete (95%) inhibition of C-peptide was achieved compared with a 57% decrease in the ob/ob mutant. Injection of ob/ob mice with glucose to counter the insulin-induced hypoglycaemia failed to affect the fall of C-peptide concentrations. The data suggest that the metabolic processing of insulin and C-peptide are undisturbed in obese-diabetic mice, and that the impaired suppression of circulating C-peptide by insulin-hypoglycaemia in ob/ob mice predominantly reflects impaired feedback inhibition by insulin.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glucose; Insulin; Kinetics; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Obese; Obesity; Radioimmunoassay

In evaluating the possibility of self-regulation of insulin secretion in man, human insulin may be more appropriate as an inhibitor to be considered than insulins from other species because the differences in the structure of the hormones might play some part in this conflicting proposal. The present study was carried out to examine whether human insulin per se can exert a feedback effect on the insulin secretion of B-cell in mild diabetics under physiologic condition. Fifteen mild diabetics were given a two-hour infusion of human insulin at a constant rate of 40 mU/m/min after a priming dose of 160 mU/m/min for the first two minutes. The plasma glucose in nine of these patients were maintained at their basal level of 92.8 +/- 3.7 mg/dL (Group A) with a glucose clamp technique (the coefficient of variation = 5.0 +/- 0.8% during the clamp), while that in the remaining six patients were intentionally altered, within physiologic range, from 114.5 +/- 8.4 mg/dL to 83.8 +/- 4.9 mg/dL (Group B). During insulin infusion the plasma immunoreactive insulin (IRI) level were well-maintained at about 50 microU/mL level in both groups, whereas the C-peptide reactivity (CPR) in group B decreased from 1.28 +/- 0.15 ng/mL to 0.59 +/- 0.14 ng/mL in parallel to the change of plasma glucose, in contrast to the relatively stable CPR level of 0.92 +/- 0.08 ng/mL in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Food; Glucagon; Humans; Islets of Langerhans; Male; Obesity

The plasma concentration of 1,5-anhydro-D-glucitol (AG) was measured in 135 newly diagnosed patients who were referred for oral glucose tolerance tests. AG concentrations in the nondiabetic patients indicated that the mean value of normal AG concentration was 21.8 micrograms/ml (SD = 5.9 micrograms/ml, range 9.6-38.8 micrograms/ml). This distribution of AG concentration was significantly different from that in patients with impaired glucose tolerance (IGT) (13.3 +/- 5.4 micrograms/ml) and definitely different from that in diabetic patients (2.1 +/- 1.8 micrograms/ml). In a standard glucagon test, it was suggested that the decrease of plasma AG was affected not only by glycemic control of the patients but also by pancreatic cell secretory activity. The reduction of AG concentration was more marked in IDDM patients than in NIDDM patients. In longitudinal studies, AG concentration was shown to be sensitive to glycemic control. However, its recovery showed a tendency toward much delay after the improvement of fasting blood glucose or HbA1 concentrations. On the other hand, AG concentration showed negligible diurnal change and no immediate change as a result of diet, oral glucose load, or acute shift of the insulin level in both normal and diabetic subjects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Blood Glucose; C-Peptide; Deoxy Sugars; Deoxyglucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged; Rats

Topics: C-Peptide; Calcinosis; Diabetes Mellitus; Glucagon; Glucose; Humans; Pancreas; Protein Deficiency

A baby boy with transient neonatal diabetes mellitus presenting with hyperglycaemia, glycosuria, and dehydration without ketonuria on the second day of life is reported. C-peptide levels were measured to aid in the assessment of insulin treatment. Very low levels were found for the first 5 months of life (less than 0.06 nmol/l). Thereafter insulin treatment was discontinued and the baby thrived showing normal growth and development at age 2 1/2 years.

Topics: Age Factors; C-Peptide; Child, Preschool; Diabetes Mellitus; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Male

We evaluated the clinical characteristics and relationships between values of serum glucose, C-peptide, and body mass index (BMI) in 40 type II diabetic patients. Patients were divided into three groups according to the drug therapy: group A (n=16), oral sulfonylurea agent; group B (n=16), insulin alone; and group C (n=8), combined insulin and oral agent. The relationships between the various factors were expressed as ratios (C-peptide/BMI, glucose/BMI, and C-peptide/glucose scores). Using glycosylated hemoglobin (HbA1) value of less than 10.5% to denote response to therapy, each group was subdivided into responders and nonresponders. Comparing the data in group A, mean (+/-SEM) fasting serum glucose levels were significantly lower in responders vs nonresponders. The mean HbA1 levels were 8.59+/-0.54% vs 1 2.34+/-0.34%, respectively. The C-peptide/BMI scores were 7.4+/-1.0 vs 8.14+/-1.2; C-peptide/glucose scores, 1.73+/-0.27 vs 0.81+/-0.12; and glucose/BMI scores, 493+/-54 vs 1,082+/-168, respectively. The responders and nonresponders in group B had values similar to those of group A. Group C patients had data A and B. The responders in each group were characterized by serum glucose levels less than 200 mg/dL, C-peptide/glucose score greater than 1, and glucose/BMI score less than 700. T he 200 mg/dL, C-peptide/glucose score less than 1, and glucose/BMI score greater than 700. These simple calculated scores validate the importance of glucose/C-peptide/BMI interrelationships in ambulatory diabetic patients.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Topics: Blood Glucose; C-Peptide; Chromatography, Gel; Chromatography, High Pressure Liquid; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Receptor, Insulin

In this assay for immunoreactive human proinsulin (IRPI), it first is separated from plasma by use of an antiserum to human C-peptide. An immunoprecipitate is then formed by using a precipitating antiserum and polyethylene glycol, after which IRPI is dissociated from the antiserum by incubation in warm HCl, pH 2.0. The resulting mixture is assayed for insulin immunoreactivity by a double-antibody tracer-competition method involving incubation for four days with a high-affinity anti-insulin antiserum. Human proinsulin of recombinant-DNA origin is used as the standard. Added C-peptide at supraphysiological concentrations did not interfere with or react in the assay. Human insulin cross reacted by 1.5%. The detection limit for IRPI (2 SD from zero-dose binding) is 3 pmol/L. Proinsulin conversion intermediates are measured nearly as well as intact proinsulin. IRPI concentrations in 10 nondiabetic human subjects averaged 12.0 (SEM 1.6) pmol/L. The ratio of proinsulin to immunoreactive insulin averaged 14.3 (SEM 2.2)%. After intravenous arginine, the increase in proinsulin was less than that of insulin, and it declined more slowly.

Topics: Arginine; C-Peptide; Cross Reactions; Diabetes Mellitus; Humans; Immune Sera; Insulin; Mathematics; Proinsulin; Radioimmunoassay

Glucose tolerance tests were performed with fourteen cynomolgus monkeys. They were divided into two groups with regard to the serum glucose level at the time of routine health-examination. Nine of them had normal glucose level (below 123 mg/dl, the normal group) and the other five monkeys exhibited hyperglycemia (the abnormal group). Fifty per cent glucose solution was administered into the saphenous vein at a dose of 4 ml/head. Blood samples were taken just before and 5, 10, 20, 30, 60 and 120 minutes after the glucose administration. K-value (K = 0.693/t 1/2 X 100) as the decreasing rate of serum glucose during from 5 to 60 minutes after the administration was calculated. Average K-value for eight monkeys of the normal group was 3.12 +/- 0.48. Both immunoreactive insulin level (IRI) and C-peptide immunoreactivity (CPR) increased just after the glucose administration and began to decrease 5 to 30 minutes after the administration in all the eight animals. Remaining one animal (No. 009) of the normal group showed 1.03 in K-value. For the abnormal group, K-value averaged 0.75 +/- 0.25. IRI was slightly higher in this group than in the 8 monkeys of the normal group. Furthermore, the abnormal group did not show any definite change of a certain trend in IRI and CPR. In conclusion, the former 8 monkeys were judged to be normal in the function of pancreatic beta-cells, and the latter 5 monkeys and No. 009 monkey were judged to be suffering from type II (noninsulin dependent) diabetes mellitus at different stages of the disease.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Insulin; Macaca; Macaca fascicularis; Monkey Diseases; Obesity; Pancreas

Insulin secretion, work capacity and plasma lipids were evaluated in 52 middle-aged men with impaired glucose tolerance (IGT), and the values were compared with those of 23 normoglycemic subjects with family histories of Type 2 diabetes and of 22 non-hereditary normoglycemic controls. All subjects were non-obese males of comparable age. Estimated maximal oxygen uptake was significantly lower (p less than 0.01) and triglyceride concentrations significantly higher (p less than 0.01) in IGT individuals than in subjects of the non-hereditary normoglycemic group, while no significant differences were noted in comparison with the hereditary group. IGT individuals showed an impaired insulin response to glucose with significantly lower absolute values of insulin and C-peptide during the early phase of the oral glucose tolerance test (OGTT) than in non-hereditary normoglycemic subjects, but not significantly lower than in the hereditary group. Similarly, at most time points of the OGTT the ratios of insulin and C-peptide to glucose were significantly lower in the IGT group than in the non-hereditary group, while these differences were less pronounced in comparison with the hereditary group. These findings suggest some similarities of metabolic disturbances in lean normoglycemics with positive family histories of Type 2 diabetes and in lean IGT individuals. Family history of diabetes (both first degree and second degree only) was significantly more prevalent among IGT individuals than among normals.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Lipids; Male; Middle Aged; Oxygen Consumption; Physical Fitness; Triglycerides

Serum C-peptide levels were measured during a glucagon stimulation test in ten normal nonobese controls and 54 diabetic patients with recent onset of diabetes under 30 years of age. Diabetic patients were comprised of 13 CTPD, 23 IDDM, and 18 NIDDM. As similar to IDDM patients, serum C-peptide concentrations did not rise significantly (P greater than 0.05) in response to glucagon administration in CTPD-patients. Mean baseline and peak serum C-peptide concentrations in CTPD-patients were significantly lower (P less than 0.001) than the values in normal controls and NIDDM patients, but were significantly higher (P less than 0.05) than those in IDDM patients. We conclude that CTPD patients have partial C-peptide reserve, which may protect against ketosis and contribute to ketosis resistance in CTPD. Our results also suggest that CTPD patients require insulin treatment. Neither baseline nor peak C-peptide levels after glucagon could discriminate CTPD from IDDM and CTPD from NIDDM.

Topics: Adult; C-Peptide; Calcinosis; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Pancreatic Diseases; Tropical Climate

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Male; Middle Aged

The content of insulin and C-peptide-like immunoreactivity (CPR) were determined in the tail of pancreas from 35 autopsied diabetic and 21 non-diabetic subjects. In the 28 diabetics who had been followed for more than 6 months, the relation between the amount of insulin or CPR in the pancreas and the stability of fasting serum glucose during diabetic life before death was analyzed together with the relation between the serum CPR response to the breakfast tolerance test before death and insulin content at autopsy. As an index of the instability of the blood sugar level, the standard deviation of the mean of 15 successive determinations of fasting serum glucose was used. Both insulin and CPR content in the pancreas were significantly decreased in diabetics as compared with non-diabetics. SD of the mean fasting serum glucose and insulin or CPR content in the tail of pancreas showed a significant inverse correlation on a logarithmic scale (P less than 0.01, r = -0.704 and P less than 0.01, gamma = -0.757, respectively). Serum CPR value during the breakfast tolerance test correlated significantly with the insulin content in the pancreas of diabetic subjects. These findings suggest that one of the causes of the instability of fasting serum glucose levels is the devastation of pancreatic beta-cells and that the pancreatic insulin content is logarithmically and inversely related to fluctuations in fasting serum glucose.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fasting; Female; Food; Humans; Insulin; Liver Cirrhosis; Male; Middle Aged; Pancreas

Polycythaemia in the neonate is a serious pathologic entity which occurs particularly in infants of diabetic mothers (IDM) and small-for-gestational age (SGA) infants. Both of these conditions are associated with fetal hyperinsulinaemia. Cultures of cord blood mononuclear cells from polycythaemic IDM showed increased growth of late erythroid progenitor colonies, compared to cord blood mononuclear cells from non-polycythaemic infants, reflecting a possible expansion of this progenitor population in the polycythaemic fetus. No changes were observed in early erythroid progenitor populations. Biosynthetic human insulin at physiological levels characteristic of IDM stimulated growth in culture of late erythroid progenitors in cord blood from premature, term and IDM infants. Three out of five polycythaemic infants had elevated cord blood plasma levels of insulin C-peptide at birth, whereas no infant with a haematocrit of less than 65% had high insulin C-peptide measurements. These data suggest that the polycythaemia noted in infants of diabetic mothers may be secondary, in large part, to a stimulatory effect on erythroid progenitor growth by the hyperinsulinaemic environment in which they develop in utero.

Topics: C-Peptide; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Diabetes Complications; Diabetes Mellitus; Female; Fetal Blood; Hematopoietic Stem Cells; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Insulin; Polycythemia; Pregnancy; Pregnancy in Diabetics

The levels of plasma insulin and C-peptide during exercise and subsequent recovery have been determined in obese non-diabetics, obese diabetics Type II and middle-aged female controls. It has been found that exercise reduces levels of peptides both in the control and in the obese non-diabetic group. This effect of acute exercise was found blunted in the obese diabetic group. Non-diabetic obese subjects pretreated with phentolamine showed no reduction either in plasma insulin or C-peptide levels during exercise. During the recovery, the level of plasma insulin returned promptly to the pre-exercise value in the control group but increased above the resting value in obese subjects, both non-diabetic and diabetic. In controls and non-diabetic obese the increment of C-peptide: insulin molar ratio occurred early after the onset of exercise and then returned to the resting value despite the exercise being continued. The plasma C-peptide:insulin molar ratios were reduced during the first 15 min of recovery period in obese non-diabetic subjects and returned to normal in the next 15 min. The latter may suggest that reduced insulin removal could also contribute to the increase in plasma insulin values in the obese during recovery.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Middle Aged; Obesity; Phentolamine; Physical Exertion

Topics: C-Peptide; Diabetes Mellitus; Erythrocytes; Humans; Insulin; Receptor, Insulin

Pancreatic beta cell function in response to glucose was assessed in three different groups of offspring of conjugal diabetic parents (OCDP): those with normal glucose tolerance, those with impaired glucose tolerance (IGT), and those with diabetes. Serum immunoreactive insulin (IRI), C-peptide (CP), insulin/glucose (I/G) ratio, and IRI/CP ratios were estimated at fasting and 90 min after glucose load. Insulin secretion, measured as CP, was found to be low even in normal nonobese OCDP, but the change was not reflected in IRI value as the IRI/CP ratio was found to be elevated. The values decreased with increasing glucose intolerance. In obese OCDP, all the parameters were abnormal even among those with normal glucose tolerance, and further deterioration occurred with increasing glucose intolerance. The study shows that insulin secretory defects are detectable even in normal OCDP, and these changes deteriorate with increasing glucose intolerance. Differences are noted in the peripheral concentrations of IRI and CP between obese and nonobese OCDP before development of diabetes. After development of diabetes mellitus, these differences disappear, and the CP and IRI values in both groups are similar and low.

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; India; Insulin; Male; Obesity

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet, Reducing; Female; Humans; Obesity

To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-3H- and 6-3H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg X kg-1 X min-1). We determined true glucose production and irreversible glucose uptake using 6-3H-glucose and glucose cycling (difference between 2-3H- and 6-3H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18 +/- 0.15 vs 1.85 +/- 0.03 mg X kg-1 X min-1, p less than 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 +/- 0.08 vs 0.25 +/- 0.07 mg X kg-1 X min-1, p less than 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 +/- 0.05 vs 0.24 +/- 0.05 mg X kg-1 X min-1, p less than 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.

Topics: Acromegaly; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose Tolerance Test; Glucose-6-Phosphate; Glucosephosphates; Humans; Insulin Resistance; Liver; Male; Middle Aged

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Middle Aged; Obesity

We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded.

Topics: Adrenocorticotropic Hormone; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Male; Obesity; Pancreatic Polypeptide

In 11 persons with normal pancreas function and 21 patients with chronic pancreatitis serum levels of insulin and C-peptide were measured under basal conditions and after maximal stimulation with glucose-tolbutamide-glucagon. Patients with the highest excretory deficiency in the secretin-pancreozymin test had the most marked impairment in endocrine function. In patients with manifest diabetes the exocrine capacity was reduced to an average of 10% of normal. The endocrine parameters correlated linearly with the exocrine ones, most markedly C-peptide reserve with pancreatic enzyme secretion.

Topics: Adult; C-Peptide; Chronic Disease; Chymotrypsin; Diabetes Mellitus; Female; Humans; Insulin; Male; Pancreas; Pancreatitis; Trypsin

In order to assess the validity of WHO criteria for the discrimination between Type I and Type II diabetes a cross-sectiona clinical study was performed in 84 normweight newly diagnosed diabetics with a mean age of 22 years. Taking into consideration clinical and biochemical characteristics of the carbohydrate and fat metabolism, the therapeutic requirement to maintain euglycemic metabolic control, the residual beta-cell function, the HLA phenotype and islet cell antibodies (ICA, ICSA) it could be shown that none of the tested criteria has the ability to distinguish between the types with absolute certainty. As shown by the frequency of the different markers in relation to the therapeutic requirements for euglycemic metabolic control as well as by the correlation analysis between the variables the discriminating validity of the markers decreased in the following sequence: diabetes associated HLA phenotype, residual beta-cell function, proneness to ketosis, age at onset, relative body weight. Neither the characteristics of the carbohydrate and fat metabolism nor the presence of islet cell antibodies contributed much to the differentiation between insulin-dependent and noninsulin-dependent diabetes.

Topics: Adolescent; Adult; Aged; Antibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Evaluation Studies as Topic; Fasting; Female; HLA Antigens; Humans; Islets of Langerhans; Male; Middle Aged; Phenotype; Time Factors; World Health Organization

To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Eating; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Liver Cirrhosis; Male; Middle Aged

Serum lipids and lipoproteins were measured in 170 insulin-treated diabetics (90 females, 80 males) and in 124 nondiabetic control subjects (59 females, 65 males) aged 45 to 64 years. Plasma C-peptide response to intravenous (IV) glucagon was measured in order to classify the patients according to their capacity of endogenous insulin secretion. In both sexes, HDL and HDL2 cholesterol were higher in diabetics with no C-peptide response than in controls, whereas diabetics with high C-peptide response (postglucagon C-peptide level greater than 0.60 nmol/L) showed lower levels of HDL and HDL2 than nondiabetic controls. When adjustment for age, alcohol consumption, physical activity, body mass index, and insulin dose was made by analysis of covariance, the highly significant difference in HDL and HDL2 cholesterol level between diabetics with no C-peptide response and diabetics with high C-peptide response still remained in both sexes. This study gives support to the hypothesis that elevated HDL and HDL2 cholesterol levels in insulin-treated diabetics are not explained by effects of treatment with exogenous insulin, but rather are associated with the type of diabetes characterized by deficient endogenous insulin secretion.

Topics: Body Weight; C-Peptide; Cholesterol, HDL; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Insulin Secretion; Lipoproteins; Lipoproteins, HDL; Lipoproteins, HDL2; Lipoproteins, HDL3; Male; Middle Aged; Triglycerides

We studied two obese type II diabetic patients before, during, and after 3 yr of continuous iv insulin infusion, delivered by means of totally implanted insulin infusion pumps. Tolerance of the devices was excellent, and no side-effects or episodes of significant hypoglycemia occurred. Glycosuria was eliminated, and mean 24-h plasma glucose and hemoglobin A1c levels decreased in both patients and remained in or near the normal range for 3 yr. Improvements were also noted in serum triglyceride concentrations and vitreous fluorescein concentrations after iv fluorescein injection. Euglycemic insulin clamp studies showed that no significant change in glucose disposal rate occurred after 6 and 12 months of treatment. However, some improvement in insulin secretion during hyperglycemic insulin clamp studies occurred in both patients after 6 months of insulin infusion. Evaluation of the insulin-glycerol mixture used in the pump revealed that moderate degradation of insulin occurred in the pump during the 21-day flow cycle, resulting in 6-12% increases in fasting blood glucose levels; in addition, higher mol wt species of immunoreactive insulin were present in the patients' serum. We conclude that long term continuous iv infusion of insulin using a totally implantable infusion pump is practical in type II diabetic patients, is acceptable to patients, and is capable of providing near-normal glycemic control.

Topics: Blood Glucose; C-Peptide; Chromatography, Gel; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycerol; Humans; Insulin; Insulin Antibodies; Insulin Infusion Systems; Male; Middle Aged; Obesity; Time Factors

To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.

Topics: Adult; Biological Transport, Active; Blood Glucose; Body Composition; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Food; Humans; Insulin; Lipid Metabolism; Male; Obesity

The determination of serum C-peptide has been found to be a sensitive indicator of endogenous insulin secretion, and serves to define diabetic patients who require insulin therapy i.e., insulin-dependent (Type I, IDDM) and those non-insulin dependent (Type II, NIDDM). The aim of our study is to establish the types of diabetes mellitus with C-peptide measurement in a group of diabetic subjects on different modes of therapy. Eighty-eight diabetic patients (60 males, 28 females) were studied. Thirty-four were on insulin (age 40 +/- 2 years; means +/- SEM), 35 on oral agents (54 +/- 1 years), and 19 on diet alone (46 +/- 3 years). Twenty healthy subjects (10 males, 10 females) serve as normal controls (37 +/- 3 years). Blood samples for serum C-peptide and blood glucose estimations were obtained after an overnight fast and one hour after a 75 grams oral glucose load. Fasting C-peptide levels obtained for the various groups were: 0.62 +/- 0.07 (nmol/L, means +/- SEM) (normal), 0.16 +/- 0.02 (insulin), 0.79 +/- 0.06 (oral), 2.15 +/- 0.15 (diet). The C-peptide values after oral glucose were 1.80 +/- 0.20 (normal), 0.23 +/- 0.05 (insulin), 1.72 +/- 0.02 (oral), 2.15 +/- 0.15 (diet). Both the fasting and post-glucose C-peptide concentrations were significantly lower (p less than 0.001) in the insulin group compared to the normals, whereas values for the diet and oral groups were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Singapore

Immunoreactive Insulin and C-peptide responses to glucose load were estimated in patients with cystic fibrosis and in controls. Both insulin and C-peptide responses were low in cystic fibrosis patients and the changes were more marked in those with glucose intolerance. There appears to be true pancreatic hyposecretion of insulin in patients with cystic fibrosis whereas the peripheral sensitivity of insulin seems to be normal or enhanced.

Topics: Adolescent; Adult; C-Peptide; Child; Cystic Fibrosis; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Reference Values

Topics: Animals; Blood; C-Peptide; Cell Division; Cell Separation; Culture Media; Diabetes Mellitus; Glucocorticoids; Glucose; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Mice; Organ Culture Techniques; Rats; Thyrotropin-Releasing Hormone

Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.

Topics: C-Peptide; Cholesterol; Diabetes Complications; Diabetes Mellitus; Female; Humans; India; Male; Nutrition Disorders; Pancreatic Diseases; Socioeconomic Factors

We have estimated the prevalence of diabetes and impaired glucose tolerance from the Busselton 1981 Population Survey using the 1980 World Health Organization (WHO) criteria. Standardized to the Australian non-Aboriginal population aged 25 years and over, the prevalence rates in this white community were 2.5% for known diabetes; 0.9% for newly discovered diabetes; 2.9% for impaired glucose tolerance; and 6.3% for all categories of abnormal glucose tolerance. There appears to have been a real increase in the frequency of diabetes since 1966. Using fasting serum C-peptide values and clinical criteria, 14% of all diabetic subjects were insulin-dependent. The male:female ratio for all categories of abnormal glucose tolerance was 1.4:1. Data from the United States indicate spectacularly higher rates for diabetes and impaired glucose tolerance in the white population. A national study of the prevalence of diabetes and impaired glucose tolerance in Australia is recommended. For epidemiological purposes, a single blood glucose value two hours after a 75 g oral glucose tolerance test is sufficient to categorize glucose tolerance as defined by WHO.

Topics: Adult; Age Factors; Aged; Australia; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Tolerance Test; Health Surveys; Humans; Male; Middle Aged; Prediabetic State; Sex Factors; Surveys and Questionnaires

A sensitive radioimmunoassay (RIA) for canine C-peptide (CCP) was established using synthetic CCP, a specific antiserum, and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine-T method. Tracer preparations were used for long as 6 weeks after iodination. The standard curve ranges from 0.028 to 3.0 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.3 and 0.8 nmol/l. The average recovery of CCP added to plasma samples was 100.6% (n = 9). Canine insulin, porcine proinsulin, bovine proinsulin, and human C-peptide exhibited no cross-reactivity. The mean fasting plasma CCP concentration was 0.089 +/- 0.021 nmol/l in normal dogs and -0.005 +/- 0.007 nmol/l (mean +/- SEM) in diabetic dogs, respectively.

Topics: Animals; C-Peptide; Diabetes Mellitus; Dogs; Guinea Pigs; Rabbits; Radioimmunoassay

One hundred consecutive patients with nonautoimmune chronic active hepatitis (51% HBsAg-positive), 50 patients with cirrhosis (38% HBsAg-positive), 25 patients with chronic persistent hepatitis, and 118 patients with hepatoma who were seen at this hospital were reviewed to determine the prevalence and characteristics of glucose intolerance and diabetes in these conditions. Diabetes (fasting serum glucose greater than 7.8 mmol/L, 140 mg/dl on two separate occasions) was present in 8% of patients with chronic persistent hepatitis and mild chronic active hepatitis, 44% of patients with severe chronic active hepatitis, 40% of patients with cirrhosis, and 15% of patients with hepatoma, compared with 7% of all other patients aged 35 yr or over, undergoing liver biopsy. Compared with this high prevalence of diabetes in liver disease, only 3% of diabetic patients referred to the hospital diabetic clinic had chronic hepatitis or cirrhosis. Glucose tolerance was similar in chronic active hepatitis and cirrhosis and was characterized initially by basal hyperinsulinemia, normal basal glucose levels but elevated serum glucose following glucose loading, and evidence of insulin resistance. We suggest that the high prevalence of diabetes in chronic active hepatitis and cirrhosis in Saudi Arabia is due to the insulin resistance of chronic liver disease acting over many years in a population with a high genetic predisposition to diabetes.

Topics: Adrenal Cortex Hormones; C-Peptide; Carcinoma, Hepatocellular; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Infant; Insulin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

We have identified a patient with mild diabetes, marked fasting hyperinsulinemia (89 to 130 microU of insulin per milliliter), and a reduced fasting C-peptide: insulin molar ratio of 1.11 to 1.50 (normal, greater than 4). The patient responded normally to exogenous insulin. However, her endogenous immunoreactive insulin showed reduced biologic activity during a glucose-clamp study with hyperglycemia and a reduced ability to bind to the insulin receptor and stimulate glucose transport in vitro. Family studies showed that five additional relatives in three generations had variable degrees of glucose intolerance, marked hyperinsulinemia, and a reduced peripheral C-peptide:insulin molar ratio. Restriction-endonuclease cleavage of DNA isolated from circulating leukocytes in the patient and in family members with hyperinsulinemia revealed loss of the MboII recognition site in one allele of the insulin gene--consistent with a point mutation at position 24 or 25 in the insulin B chain. Other studies using high-pressure liquid chromatography and detailed gene analysis have identified the defect as a serine for phenylalanine substitution at position 24 of the insulin B chain. The secretion of a structurally abnormal insulin should be considered in patients with hyperinsulinemia who respond normally to exogenous insulin and have a reduced C-peptide:insulin molar ratio. Glucose tolerance may range from relatively normal to overtly diabetic.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Mutation; Receptor, Insulin

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged

Plasma concentrations of pancreatic glucagon, C-peptide, and pancreatic polypeptide were measured during arginine stimulation in 16 patients with chronic pancreatitis, in eight subjects with idiopathic diabetes mellitus, and in seven healthy controls. The hormone responses were compared with exocrine pancreatic function as assessed using the urinary excretion rate of p-aminobenzoic acid after oral ingestion of n-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). The increase in pancreatic glucagon levels during arginine stimulation was significantly reduced in patients with chronic pancreatitis compared to healthy controls, most markedly in those with secondary diabetes. In contrast, the glucagon response was unimpaired in patients with idiopathic diabetes. The arginine-induced increase in plasma glucagon and C-peptide concentrations correlated significantly with urinary PABA excretion in chronic pancreatitis (P less than 0.001, P less than 0.01, respectively). The responses of plasma C-peptide and pancreatic polypeptide separated pancreatitic and idiopathic diabetes less well. Thus, the glucagon response to arginine distinguished secondary diabetes due to chronic pancreatitis and idiopathic diabetes mellitus. The correlation between urinary PABA excretion and glucagon levels suggests that in chronic pancreatitis there is a parallel impairment of exocrine and endocrine function.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Arginine; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; para-Aminobenzoates

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.

Topics: Adult; C-Peptide; Cadaver; Diabetes Mellitus; Diabetic Nephropathies; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Insulin; Jejunum; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Pancreas; Pancreas Transplantation; Pancreatic Ducts; Postoperative Care; Tissue Donors; Uremia

Changes in the secretion and metabolism of insulin were measured by estimating serum C-peptide and insulin and their ratio during oral GTT in 30 non obese and 12 obese NIDDM patients. The mean IRI and CP responses were low in both groups of patients, compared to weight-matched controls. The reduction in CP was more marked than the reduction in IRI. The molar ratio of insulin and CP was found to be elevated in the patients, probably indicating reduced hepatic and peripheral extraction of insulin. It was noted that the elevated IRI/CP ratio was a 1) a common feature in NIDDM, irrespective of the body weight, 2) it is present even under basal conditions when the insulin levels are the lowest, 3) it appears to be independent of the concentration of insulin reaching the liver, and 4) obese patients appear to have an exaggerated defect compared to their non obese counterparts.

Topics: Adult; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Liver; Male; Middle Aged; Obesity

Monthly determination of glycohaemoglobins from the 5th month until delivery were determined in a group of diabetic pregnant women, and insuline and peptide-C levels were measured in their newborns. Women with pathological babies had higher glycohaemoglobin values at the end of gestation (8.92 +/- 1.9) than those with normal babies (6.47 +/- 1.02) and those in control group (6.37 +/- 0.76). The number of abnormal glycohaemoglobin levels in successive gestational months was significantly higher in the group with neonatal pathology. The peptide-C and insuline concentrations were higher in pathological newborn (6.37 +/- 9,3 ng/ml and 80 +/- 102 mcU/ml) than in normal babies (0.65 +/- +/- 0.53 ng/ml and 16.5 +/- 10.6 mcU/ml). A correlation between peptide-C concentration in newborns and levels of glycohaemoglobins in their mothers (p less than 0.05) was found. Authors conclude that monthly determination of glycohaemoglobin during gestation is a good index of metabolic control in the mother, and consequently useful in order to predict fetal pathology.

Topics: C-Peptide; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Pregnancy; Pregnancy in Diabetics

To assess the effects of metabolic control upon beta cell function in diabetes, pro-insulin and insulin were determined following gel-filtration of plasma at two time points in each three diabetic patients, once when the metabolic state was severely deranged and again after the metabolic state had improved after therapy. Before therapy, proinsulin concentration were 30 pM (as IRI), both fasting and at 2 hours after an oral glucose load. These values did not change with treatment. Insulin concentrations were 22 pM at both time points before therapy. With treatment, plasma insulin increased 2-fold at fasting and 7-fold at 2 hours after oral glucose. These results suggest an exhaustion of the insulin pool in beta cells during severe metabolic decompensation of diabetes, a condition which may be reversed by correction of the metabolic states of the patients with proper therapy.

Topics: Acromegaly; Adult; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Proinsulin

Diabetic hyperosmolar coma is a syndrome of marked hyperglycemia and minimal ketoacidosis. In general, the serum glucose concentrations are not predictive of the serum ketoacid concentrations in acutely decompensated diabetes. The endocrine factors that modulate glucose concentrations may be different from those that modulate ketoacid concentrations in patients with acutely decompensated diabetes. To test this hypothesis, regression analysis was used to determine the endocrine and metabolic characteristics that correlated with serum concentrations of glucose and ketoacids in 26 diabetic patients with spontaneous, acute hyperglycemia. All patients had a serum glucose level greater than 390 mg/dl, and ketoacid levels were from 0.17 to 25.5 mM. Multiple regression analysis showed that increased serum glucose concentrations correlated with increased plasma glucagon levels (p = 0.0007, r2 = 0.45), but with no other factors. Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72). Body mass index only correlated with ketoacid levels, when it was analyzed with C-peptide and free fatty acid levels. A model is proposed that predicts the serum glucose and ketoacid concentrations in patients with acutely decompensated diabetes. Glucagon modulates the serum glucose concentration in these patients with an absolute or relative insulin deficiency. Total serum ketoacid levels are determined by the serum free fatty acid concentration, residual pancreatic insulin secretion (as reflected by C-peptide), and the patient's body habitus. This model allows for the marked hyperglycemia and minimal ketosis of diabetic nonketotic hyperosmolar coma, as well as the glucose and ketoacid concentrations in other presentations of acutely decompensated diabetes.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Coma; Diabetic Ketoacidosis; Fatty Acids, Nonesterified; Female; Glucagon; Growth Hormone; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Keto Acids; Male; Middle Aged; Models, Biological; Regression Analysis

Fasting serum C-peptide immunoreactivity was determined on Nauruans, a Micronesian population with a high prevalence of diabetes. In Micronesian subjects neither age nor gender had a significant effect on fasting serum C-peptide. In non-diabetic subjects, as has been shown previously for Caucasiod subjects, both obesity and fasting plasma glucose levels were determinants of fasting serum C-peptide. Obesity was the major determinant. Taken overall, mean fasting serum C-peptide increased then possibly fell in subjects grouped by increasing 2-h post-glucose plasma glucose levels. Mean fasting serum C-peptide in newly-diagnosed diabetic subjects was greater than that in non-diabetic subjects with a similar degree of obesity, supporting the concept that the transition to diabetes may be associated with an increase in insulin resistance. The data for non-diabetic subjects were compared with serum C-peptide measured in the same laboratory on samples from a Caucasoid population in Busselton, Western Australia. There was no difference in fasting serum C-peptide level between Micronesian and Caucasoid subjects approximately matched for obesity and fasting plasma glucose levels.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Fasting; Female; Humans; Male; Micronesia; Middle Aged; Obesity; Racial Groups

The effect of mild hypercalcaemia on the growth hormone (GH), C-peptide and glucose responses to arginine infusion in patients with insulin-dependent idiopathic diabetes mellitus (ID) was compared with that observed in patients whose diabetes was secondary to idiopathic haemochromatosis (IH) and chronic pancreatitis (CP). The summated GH responses to arginine infusion alone were similar in all three groups. Mild hypercalcaemia significantly diminished the GH response to arginine in patients with secondary diabetes, but not in those with ID. As the blood glucose and C-peptide responses were similar in the presence of a normal or raised serum calcium, the differences in GH response could not be ascribed to changes in blood glucose levels or to alterations in endogenous insulin release. For reasons as yet unknown, hypercalcaemia appears to have more of a stabilizing effect on the pituitary somatotrophic granules of those with secondary diabetes than in those with ID.

Topics: Adult; Arginine; C-Peptide; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Female; Growth Hormone; Hemochromatosis; Humans; Hypercalcemia; Male; Middle Aged; Pancreatitis

Topics: Acromegaly; Adult; Bromocriptine; C-Peptide; Carbohydrates; Diabetes Mellitus; Drug Evaluation; Female; Glucagon; Glucose Tolerance Test; Growth Hormone; Humans; Insulin Antibodies; Male; Middle Aged; Pancreas

24 diabetic patients stabilised on conventional bovine insulins and possessing insulin antibodies underwent a study of the immunological and clinical consequences of changes in both purity and species of their insulin preparations. After a 2-month run-in period patients were treated for 3 consecutive 4-month periods with (a) purified bovine insulin (20-40 ppm proinsulin), (b) highly purified porcine insulin, and (c) semisynthetic human insulin, without elective dose changes. Mean insulin antibody levels changed little on purified bovine insulin (22.2 leads to 23.4 micrograms/l) but fell on highly purified porcine (23.4 leads to 12.9 micrograms/l) and remained much the same on Semi-Synthetic human insulin. In contrast, C-peptide antibodies fell significantly and continuously throughout the study. The slower rate of fall in C-peptide antibody levels is likely to be due to the prolonged half-life of circulating exogenous proinsulin in the presence of insulin antibody. Although insulin dose remained constant the incidence of hypoglycaemic episodes did not increase and glycosylated haemoglobin levels rose significantly when patients were on porcine insulin. The deterioration in diabetic control may have been due to greater temporal mismatch between insulin needs and insulin availability with pork or human insulin than with beef insulins, and to reduced insulin antibody levels. The use of purer insulins which more closely resemble the human form can cause a significant reduction in levels of insulin and C-peptide antibodies. Although these changes may have other benefits they do not necessarily produce better diabetic control. Subcutaneous insulin regimens need to be tailored to the individual patient and, indirectly, to his antibody status.

Topics: Animals; C-Peptide; Cattle; Diabetes Mellitus; Hemoglobin A; Humans; Immunoglobulin G; Insulin; Insulin Antibodies; Peptides; Proinsulin; Swine

Antibodies to insulin were found in 92% of the 138 insulin-treated pregnant diabetic patients studied. No effect of pregnancy was shown on insulin antibody levels. Higher insulin antibody levels were significantly associated with the previous use of conventional insulins. Change from conventional to highly purified porcine insulin during pregnancy produced a significant reduction in insulin antibody levels. The combination of protamine zinc and soluble insulin used before pregnancy was found to be the most immunogenic. Insulin antibodies were freely transferred to the fetus but not detectable after the first 8 months of life. No insulin antibodies were found in the cord blood or during the next few weeks in the infants of mothers who had no antibodies to their injected insulin. There was a tendency for higher insulin antibody levels to be associated with indices of neonatal morbidity but not with percentile birth weights and C-peptide levels in cord sera.

Topics: Animals; Antibodies; Birth Weight; C-Peptide; Cattle; Diabetes Mellitus; Epitopes; Female; Fetal Blood; Fetal Death; Humans; Insulin; Maternal-Fetal Exchange; Postpartum Period; Pregnancy; Pregnancy in Diabetics; Swine

Various immunological mechanisms help to understand the epidemiological and biological heterogenicity of type 1 Diabetes Mellitus. Immunological mechanisms are involved in the destruction of beta cells and perhaps explain the prevalence of Diabetes Mellitus among certain patients with well defined genetic markers. Certain cases of Diabetes Mellitus seem to be mediated by auto-immune processes (cellular or humoral) and thus have a common denominator with other endocrinological diseases. Other immunological mechanisms are incriminated in the development of insulin resistance during exogenous insulin treatment of type 1 Diabetes Mellitus. Resistance to endogenous insulin which characterizes type 2 Diabetes Mellitus is related to a decrease in number and density of peripheral insulin receptors.

Topics: Animals; C-Peptide; Diabetes Mellitus; HLA Antigens; Humans; Insulin Resistance; Islets of Langerhans; Virus Diseases

In a study of 102 patients (64 women and 38 men; 63 whites and 39 nonwhites; 77 with adult-onset disease and 25 with juvenile-onset disease), the data, after being adjusted for age, showed that diabetic peripheral neuropathy was associated with diabetic keratopathy. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than .01); the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were reduced tear break-up time (P less than .03), the type of diabetes (P less than .01), and metabolic status, shown by fasting C-peptide levels (P less than .01). No significant relationships were found between keratopathy and tear glucose levels, endothelial cell densities, corneal thickness, or duration of disease.

Topics: Aged; C-Peptide; Corneal Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Triglycerides; Vibration

We have determined total body carbohydrate and lipid oxidation rates in response to a standard breakfast in nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in seven age- and weight-matched controls. The patients with NIDDM were studied twice, once while in poor glycemic control (fasting blood glucose concentration 267 +/- 24 mg/dl, urinary glucose excretion 28.9 +/- 6.3 g/24 h) and again after modest glycemic improvement following 2 mo of fiber treatment (fasting blood glucose 227 +/- 19 mg/dl, urinary glucose excretion 10.7 +/- 1.9 g/24 h). Basal carbohydrate (CHO) oxidation rates were normal in patients with NIDDM before and after fiber treatment. However, in patients before fiber treatment the rise in CHO oxidation rates, the reciprocal fall in lipid oxidation rates, and the rise in serum insulin and C-peptide concentrations after the breakfast were all severely blunted. In addition, storage of ingested CHO was significantly reduced (from 55% to 32%, P less than 0.05). After fiber treatment, postbreakfast CHO oxidation rates had improved and were no longer significantly lower than control values. In contrast, CHO storage remained suppressed. We conclude that (1) basal CHO oxidation remained normal but that postbreakfast CHO oxidation was impaired in our obese patients with NIDDM. This impairment, however, appeared to be a relatively late event, occurring only during severely uncontrolled NIDDM. (2) Inability to dispose of CHO by storage appeared to be an earlier defect with a greater impact on glucose tolerance than the impairment of CHO oxidation.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Calorimetry; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fiber; Eating; Fatty Acids, Nonesterified; Female; Humans; Insulin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxidation-Reduction

To evaluate the roles of counterregulatory hormones and insulin antibodies in the impairment of plasma glucose recovery from hypoglycemia in diabetes mellitus, and to assess the relationship between the glucagon response and duration of the disease, 21 insulin-dependent diabetic patients and 10 nondiabetic subjects were studied. The diabetics consisted of 5 patients with recent onset of diabetes (less than 1 mo); 11 with 2.6 +/- 0.3 (mean +/- SEM) yr duration of diabetes, 5 of whom had insulin antibodies; and 5 patients with long-term diabetes (21 +/- 3 yr), insulin antibodies, and autonomic neuropathy. During insulin-induced hypoglycemia (28 mU/m2 X min for 60 min) in patients with recent-onset diabetes, plasma free insulin, glucose, and counterregulatory hormone concentrations did not differ from those of nondiabetic subjects. In patients with insulin antibodies, the disappearance of insulin after insulin infusion was delayed, and both restitution of normoglycemia and plasma glucagon response were blunted compared with patients without antibodies. When glucagon was infused (80-130 ng/m2 X min) during hypoglycemia in diabetics with impaired glucagon responses in order to simulate normal glucagon responses, plasma glucose recovery was normalized in patients without antibodies but not in those with antibodies. In patients with long-standing diabetes, restitution of normoglycemia was further impaired and this was associated with an absent plasma glucagon response and a diminished plasma epinephrine response. Plasma glucagon responses to hypoglycemia were inversely correlated to the duration of diabetes (r = -0.943; P less than 0.0005). It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses. Slowed disappearance of insulin due to the presence of insulin antibodies further delays the restoration of normoglycemia. Patients with long-standing diabetes and autonomic neuropathy exhibit decreased epinephrine secretion, which leads to an additional retardation of glucose recovery. Since plasma glucagon and epinephrine responses to hypoglycemia were normal at the onset of diabetes but diminished in long-term diabetes, it appears that the impaired glucagon and epinephrine responses to hypoglycemia are acquired defects that develop subsequent to B-cell failure.

Topics: Adolescent; Adult; Antibodies; Blood Glucose; Body Surface Area; Body Weight; C-Peptide; Diabetes Mellitus; Epinephrine; Glucagon; Humans; Hypoglycemia; Insulin; Islets of Langerhans

To investigate the mechanism of elevated plasma triglycerides in non-insulin-dependent (type II) diabetes, very-low-density lipoprotein triglyceride (VLDL-TG) metabolism was studied in 10 untreated male Pima Indian diabetics and compared with that of 15 weight-matched male nondiabetic controls. VLDL-TG metabolism was studied using tritiated glycerol as an endogenous precursor of VLDL-TG, and the resultant kinetic data were analyzed using a multicompartmental model, which includes two pathways for VLDL-TG synthesis and a stepwise delipidation process for VLDL catabolism. Pima diabetics had VLDL-TG concentrations approximately 150% those of nondiabetics. Rates of VLDL-TG production in the diabetics were not significantly different from those of controls. On the other hand, the fractional catabolic rate for VLDL-TG was significantly lower in the diabetics compared with the nondiabetics. Other catabolic parameters, such as the fraction of VLDL-TG delipidized at each step and the stepwise delipidation rate, were also decreased in the diabetics. To determine the relationships between the increased triglycerides and determinants of lipid metabolism that are altered in diabetes, insulin and free fatty acid concentrations were also assessed. Basal C-peptide levels in the diabetics during the metabolic study were slightly but not significantly higher than those of the nondiabetics. There was a highly significant correlation in the diabetics between plasma C-peptides and VLDL-TG production, whereas VLDL production in Pima nondiabetics was not related to insulin levels. Free fatty acid levels were not significantly elevated in the Pima diabetics. The data indicate that (1) the rise in VLDL-TG in Pima diabetics was a result of decreased capacity for clearance and (2) the absence of elevated VLDL-TG production may be attributed to the lack of increase in free fatty acids.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Glucose; Humans; Insulin; Lipoproteins, VLDL; Male; Middle Aged

Endoscopic retrograde pancreatography (ERP) was performed in 48 patients who had been hospitalized for pancreatitis. The findings were related to results of oral glucose tolerance tests. Patients with gross changes at ERP tended to have latent or manifest diabetes. In patients with latent or manifest diabetes, the increase in C-peptide after oral glucose was lower than in healthy subjects, while insulin sensitivity, estimated with euglycemic insulin clamp technique, was within the same range as in healthy subjects. It is concluded that gross changes of the pancreatic ducts after pancreatitis are often accompanied by widespread tissue damage leading to deficient B-cell function and decreased glucose tolerance.

Topics: Adult; Aged; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

Topics: Age Factors; C-Peptide; Diabetes Mellitus; Humans; Hypoglycemia; Insulin; Islets of Langerhans

The release of immunoreactive gastric inhibitory polypeptide (IR-GIP) in response to a standard meal was examined in 10 normal subjects and 15 type I (insulin-dependent) diabetics 7 days (test I), 14 days (test II), and 3 months (test III) after time of diagnosis. During all three tests, the diabetics had significantly lower plasma IR-GIP concentrations than the controls from 15-90 min after the standard meal. The IR-GIP response in the diabetics measured as the integrated area under the response curve corresponded to 70% of that of normal subjects. beta-cell function evaluated from the C-peptide response to the meal increased significantly from test I to test III whereas the IR-GIP response was similar during all three tests. As GIP is known to potentiate glucose-induced insulin secretion and possibly the biosynthesis of insulin, the low IR-GIP responses in subjects with type I diabetes may significantly influence insulin levels and hyperglycemia.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diet; Food; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Humans; Insulin; Time Factors

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.

Topics: Adolescent; Adult; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Liver; Male; Middle Aged; Obesity

The pancreatic B-cell function (glucose tolerance, C-peptide release) and organ-specific autoantibodies, including islet cell cytoplasmic and cell surface (mouse), were studied in 45 first-degree relatives of patients with insulin-dependent diabetes mellitus diagnosed before the age of 30 years. Compared to 107 healthy persons without any family history of either insulin-dependent or non-insulin-dependent diabetes mellitus, the prevalence of autoantibodies was increased among the relatives. The prevalence of islet cell antibodies did not differ between relatives and controls and none of the individuals had complement-fixing islet cell antibodies. There was no difference in glucose tolerance or C-peptide release between relatives and controls, whether they had autoantibodies or not. At a three-year follow-up, none of the individuals had developed insulin-dependent diabetes.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male

Since the C-peptide Radioimmuno active/Immuno Reactive Insulin (CPR/IRI) molar ratio is considered as an index of insulin hepatic extraction and tissue receptor binding, the AA. investigated the effects of metformin on this index after glucagon infusion in non-insulin dependent diabetics. Fourteen lean subjects (aged 48 to 67 years, mean 54 +/- 7) with non-insulin dependent diabetes were studied. At 9.00 a.m. each subject after overnight fasting, underwent glucagon infusion (1 mg i.v. diluted in 250 ml of saline, infused at a rate of 8.3 gamma/min for 2 hours); blood specimen were obtained at --15, 0, 30, 60, 90, 120 min. This test was repeated after a five-day treatment with metformin (1.5 g per os). For each sample plasma glucose by glucose oxidase method, plasma insulin and C-peptide by Radio Immuno Assay (RIA) method were determined. After treatment with metformin the hyperglycemia induced by glucagon was not influenced; nevertheless insulin and C-peptide plasma levels showed an evident reduction while CPR/IRI molar ratio was unchanged. The AA. suppose an indirect effect of metformin upon beta cells, namely a less pancreatic insulin requirement, mediated by an improvement of glucose utilization.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Insulin; Male; Metformin; Middle Aged; Peptides; Time Factors

An assessment of beta cell and exocrine pancreatic reserve based on fasting C peptide and immunoreactive trypsin (IRT) concentrations was carried out in non-diabetic (fasting blood glucose less than 6 mmol/l) patients with cystic fibrosis (CF; n = 20) and their parents (heterozygotes; n = 26). These indices were also measured in comparable control subjects (n = 20) and insulin-dependent diabetics (IDDs). C peptide concentrations in 18 CF patients were markedly lower than those in controls, and in 18 were comparable to those in IDDs (n = 27). Fasting C peptide concentration in heterozygotes was also significantly lower than that in controls and was significantly greater than that in IDDs. IRT concentrations in CF patients and heterozygotes were also significantly lower than those in controls. The frequency of subnormal C peptide concentrations was greater in CF patients with non-measurable IRT than in those who had residual IRT in their sera. These data show for the first time that the diminution in beta cell reserve in CF patients may be of a magnitude similar to that in IDDs in spite of their normal blood glucose and HbA1 concentrations. Therefore, these patients may have enhanced insulin sensitivity. CF heterozygotes too have a significant diminution in endocrine and exocrine pancreatic reserve when compared with the controls.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Heterozygote; Humans; Islets of Langerhans; Male; Middle Aged; Trypsin

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Peptides

Fifty nine insulin dependant diabetics were hospitalised for a trial withdrawal of insulin: 17 patients rapidly showed signs of lack of insulin, 18 did not develop cetoacidosis but could not be stabilised on diet and oral hypoglycemic agents, 24 were stabilised without insulin. A statistical study (multifactorial analysis of correlations, plotting of ROC graphs) validated the classification of these diabetics into 3 groups. It also showed that in patients with hypoglycemia, the values of C-protein, and after intravenous injection of tolbutamide, were good predictive factors for insulin-dependance: all patients with basal C-protein less than 1,9 ng/ml could not be stabilised without insulin; when the basal C-protein greater than or equal to 1,9 ng/ml and the amplitude of response at the 5th min was greater than or equal to 0,4 ng/ml, the diabetes could be stabilised by diet and oral hypoglycemic agents in 90 p. 100 of cases. This institutes an easy, reliable and economic method of detecting abusive insulin therapy.

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Injections, Intravenous; Insulin; Male; Middle Aged; Peptides; Tolbutamide

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Insulin; Male; Middle Aged; Peptides

C-peptide and insulin serum determinations were performed in 94 glucagon-stimulated diabetics and in 15 healthy persons. A minimal increase of 1.5 ng C-peptide/ml serum after glucagon injection (1 mg i.v.) was found to be a useful parameter for the differentiation of insulin dependent and non-insulin dependent diabetics. The maximal response to glucagon occurred during the first 10 minutes after the injection (blood was drawn at 2-minutes intervals). Serum insulin levels and basal C-peptide concentrations were of no value in predicting insulin-dependency. Basal C-peptide levels were significantly different from control in juvenile insulin dependent diabetics (decrease) only.

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Insulin; Male; Middle Aged; Peptides

We studied the insulin sensitivity in 5 normal subjects and 5 subjects with impaired carbohydrate tolerance using the glucose controlled insulin infusion system (BIOSTATOR). During a fixed glucose infusion rate of 2 mg/kg b.w./min, the computer program was set to maintain the plasma glucose concentration at 4.44 mmol/l. The ratio of infused exogenous insulin to infused glucose served as a measure of insulin sensitivity. Calculating the average insulin glucose ratio for 24 hours, the mean values amounted to 3531 and 9319 ng/gm (p less than 0.01) in subjects with normal and impaired carbohydrate tolerance, respectively, indicating that insulin resistance is the main cause of decreased glucose utilization in the latter group. Circadian rhythms of insulin sensitivity occur in both groups in a similar fashion. The insulin sensitivity was higher in the afternoon (1200-1800) as compared to the night. Thus, diurnal variations in insulin sensitivity are independent of disturbances of glucose metabolism.

Topics: Blood Glucose; C-Peptide; Circadian Rhythm; Computers; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Infusion Systems

A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2-3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23-0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.

Topics: Acanthosis Nigricans; Adolescent; Arginine; C-Peptide; Diabetes Complications; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Resistance; Islets of Langerhans; Male; Proinsulin; Receptor, Insulin; Syndrome

The proliferative responses of IDDM or NIDDM patients and normal controls to monocomponent pork and beef insulins was assayed over a period of 5 days. No difference was detected in the proliferative responses between the groups. About 25-30% responded to insulin antigens by giving stimulation indices of 1.5 or higher. The exception was the HLA-B8/15 group of patients where no responses (less than or equal to 1.5) were observed. The evidence that the responses detected were insulin specific is discussed, as is the HLA and possible immune response gene linkage.

Topics: Adult; Aged; Animals; Antigens; C-Peptide; Cattle; Concanavalin A; Diabetes Mellitus; Diabetes Mellitus, Type 1; HLA Antigens; HLA-B Antigens; Humans; Insulin; Lymphocyte Activation; Middle Aged; Swine; Tuberculin

Topics: C-Peptide; Diabetes Mellitus; Humans; Islets of Langerhans; Triiodothyronine; Triiodothyronine, Reverse

Topics: Blood Glucose; C-Peptide; Cushing Syndrome; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Antibodies; Islets of Langerhans

The diurnal blood glucose profiles of 15 unstable diabetics were continuously monitored by the artificial endocrine pancreas (AEP, Biostator). Then, feedback control (FC) with the AEP was performed on each subject for 24-32 hr. Based on the data obtained from FC, the patients received an intensified conventional insulin therapy (ICIT) consisting of two daily mixed injections, 45-60 min prior to meals. There was a negative correlation between the MAGE and the sum of serum CPR in a 50 g OGTT, before FC. The M-value, MBG and MAGE decreased significantly during FC and remained lower one month later, compared with those values obtained before FC. The ICIT caused a noticeable decrease in HbA1 levels one to four months after FC. The ICIT was characterized by an increase in the proportion of short-acting insulin in the daily insulin dosage to 40. 3 +/- 11.5%. The proportion of daily insulin dosage to body weight also increased to 0.73 +/- 0.17 U/kg. These results suggest that the AEP, Biostator, could be useful in the clinical management of unstable diabetics by providing a more precise estimate of patients insulin requirements, especially those of short-acting insulin, leading to a better long-term control of blood glucose.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Infusion Systems; Male; Middle Aged

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Male

Topics: Animals; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Islets of Langerhans; Swine

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus; Drug Combinations; Glucagon; Humans; Insulin, Isophane; Swine

HLA antigen studies indicate heterogeneity of allele of B locus and propedine factor based on racial differences, while confirming specificity of DR3-DR4 for IDDM. C-peptide reserve is indicative of some sparing of beta cell destruction due to pre-existing nutritional state with enzymatic modulations modifying ketosis in the atypical IDDM in North India. Specific diabetic vascular disease has lesser geographical predisposition though factors that promote its severity or restrain its progress are not well understood.

Topics: Adolescent; Adult; Age Factors; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; HLA Antigens; Humans; India

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Male; Obesity; Peptides

During an exhaustive graded bicycle spiroergometer test, several arterial blood samples were taken from six type I diabetics and seven normal controls for determination of catecholamines and parameters of carbohydrate and lipid metabolism. In both groups during exercise, glucose remained unchanged, and lactate associated metabolic acidosis was compensated by respiratory gas exchange. Diabetics showed an impaired exercise-induced response of adrenaline and noradrenaline (62 +/- 8 to 176 +/- 24 and 98 +/- 6 to 612 +/- 175 pg X ml-1), respectively, compared to controls (55 +/- 6 to 1213 +/- 720 and 95 +/- 17 to 1710 +/- 506 pg X ml-1). Free glycerol increased to an equivalent extent in both groups. Simultaneously produced free fatty acids decreased at high work loads in diabetics. In addition to insulin deficiency and impaired catecholamine secretion, diabetics showed high values of growth hormone, ACTH, and cortisol. These may be responsible for the high values of free glycerol and free fatty acids. At maximum the FFA values decreased in both groups, although levels of lactate and pyruvate were high. It is suggested that insulin deficiency is the reason for the disturbed hormonal and metabolic response to exhaustive exercise and reduces physical fitness in diabetics.

Topics: Adult; Blood; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Dopamine; Epinephrine; Fatty Acids, Nonesterified; Humans; Hydrogen-Ion Concentration; Lactates; Lipid Metabolism; Male; Norepinephrine; Physical Exertion; Pyruvates

Topics: C-Peptide; Diabetes Mellitus; Female; Humans; Male; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Plasma immunoreactive glucagon, C-peptide and substrates (glucose, lactate, and alanine) were measured in 21 pancreatectomized patients and 28 patients with chronic calcifying pancreatitis during arginine infusion. Results were compared with those obtained in control and in insulin-dependent diabetic subjects, and in pancreatectomized subjects receiving a combined infusion of glucagon and arginine or somatostatin and arginine. Plasma immunoreactive glucagon in the pancreatectomized patients was 230 +/- 26 pg/ml (control subjects 100 +/- 13 pg/ml, p less than 0.001), but was unchanged following arginine or somatostatin. Following ethanol extraction of plasma it became undetectable. Similar results were obtained in patients with chronic pancreatitis. In contrast to the insulin-dependent diabetic subjects, no changes in blood glucose, lactate, and alanine concentrations were found during arginine infusion in the pancreatectomized or pancreatitis patients. Addition of glucagon restored the metabolic response to arginine in the pancreatectomized patients. Our results confirm previous smaller studies that in pancreatectomized patients, A cell function is absent or insignificant.

Topics: Adult; Arginine; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Pancreatectomy; Pancreatic Function Tests; Pancreatitis; Somatostatin

Topics: Adrenergic alpha-Antagonists; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Humans; Insulin; Insulin Secretion; Male; Nicergoline; Time Factors

To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Obesity; Splanchnic Circulation

In an attempt to determine the mechanism of decreased glucose tolerance in lean type 2 diabetics, glucose turnover in such subjects and controls was studied under basal conditions and during hyperglycemia induced by intravenous administration of glucose. The diabetics had decreased intravenous glucose tolerance and a fasting plasma glucose of 6-8 mM (108-144 mg/dl). Glucose was infused for 2 hr at 2 mg/kg per min in the controls (n = 16) and diabetics (n = 9). Furthermore, 11 healthy subjects were infused also with glucose at 4 mg/kg per min to match the glycemia of the diabetics. Glucose production, utilization, and metabolic clearance were assessed by the primed constant tracer infusion technique. In the basal state, diabetics showed normal plasma insulin, C peptide, and glucagon concentrations. Their increased basal plasma glucose levels were associated with normal rates of glucose production and utilization, but the metabolic glucose clearance was 21% lower than in the controls (P < 0.001), indicating decreased sensitivity to insulin. During infusion of glucose at 2 mg/kg per min, the hyperglycemia attained in the diabetics (170 mg/dl) was higher than that in controls (115 mg/dl) but comparable to that of the controls exposed to the higher glucose load. With the lower glucose load, metabolic clearance rate decreased more markedly in diabetics, again suggesting insulin resistance. This was further substantiated by the fact that, at the same insulin levels, glucose utilization did not increase more in the diabetics than in the controls, although the glycemia reached was considerably higher in the diabetics. With the lower glucose load, glucose production was suppressed to the same degree in the controls and diabetics, although the attained glycemia was much more marked in the latter. Because both insulin and hyperglycemia can suppress glucose production, some defect in the regulation of glucose production of the diabetics is also indicated. The insulin and C peptide levels were much higher in the controls than in the diabetics at the same levels of glycemia, demonstrating the inadequacy of insulin response to glycemia of the diabetics. Glucagon concentration was equally suppressed in all groups. In conclusion, impaired glucose tolerance of mild type 2 diabetics resulted both from inadequate insulin response and from decreased sensitivity to insulin. The insulin resistance could mainly be ascribed to inadequate glucose uptake, but a defect in glucose-ind

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Time Factors

Seven out of 206 subjects investigated at 6-mth intervals with a glucose tolerance test developed non-insulin dependent diabetes. The mean fasting serum C-peptide concentration in the diabetic subjects was greater at the time of diagnosis of diabetes than 6 mth prior to diagnosis (1.25 and 1.01 nmol/l respectively, p less than 0.05). There was no significant difference in mean ideal body weight and maximum post-glucose serum C-peptide reactivity (CPR) before and at diagnosis. There was no change in mean fasting CPR during a similar 6 mth period (0.84 and 0.84 nmol/l respectively) in 17 subjects with normal glucose tolerance matched with the diabetics for age and ideal body weight. It is postulated that at least in some subjects the transition to diabetes is accompanied by an increase in insulin resistance.

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Obesity; Quality Control; Time Factors

Topics: C-Peptide; Diabetes Mellitus; Half-Life; Humans; Insulin; Receptor, Insulin

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Peptides

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 +/- 2.1 (SE) mmol/l, and 3-hydroxybutyrate at 0.24 +/- 0.08 mmol/l. Blood lactate (1.88 +/- 0.18 mmol/l) and glycerol (0.084 +/- 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 +/- 7, 103 +/- 35, and 95 +/- 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 +/- 1.1 mmol/l (P less than 0-.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 +/- 0.02 mmol/l (P less than 0.05). Blood lactate (1.67 +/- 0.08 mmol/l) and glycerol (0.10 +/- 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 +/- 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Alanine; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glycerol; Humans; Hydroxybutyrates; Insulin; Lactates; Male; Peptides; Skin Absorption

Antibodies reactive with the C-peptide portion of proinsulin can be detected in the sera of patients on conventional bovine insulin regimes which include the soluble form. Direct and competitive binding studies demonstrate that C-peptide antibodies show species specificity but do not recognize free homologous C-peptide. This is likely to be due to conformational change following cleavage of C-peptide from the proinsulin molecule. Examination of sera from a large group of patients established on a standard insulin regime shows that C-peptide and insulin antibody levels do not correlate with each other and are likely to show different patterns of genetic control.

Topics: Animals; Antibody Specificity; C-Peptide; Cattle; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Insulin, Isophane; Insulin, Long-Acting; Peptides

Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its urinary clearance (UCI-C) is constant and unaffected by plasma C-peptide concentration, body mass, or diabetes. We measured clearance ratios of C-peptide/creatinine (CR) in the fasting state and integrated 0-1, 1-3, and 3-5 h after 100 g of glucose p.o. as well as over a full 24-h in eight obese, eight lean, and six maturity-onset diabetic subjects. CR did not differ significantly when values in the fasting state were compared with those in the postprandial periods and was therefore unaffected by plasma C-peptide concentration. Furthermore, CR was similar in the lean, obese, and diabetic subjects. SR-C, determined as the product of the metabolic clearance rate of C-peptide and its fasting or integrated plasma concentrations, correlated significantly with U-C in all the subjects (r = 0.87, P less than 0.0001). The correlation of U-C with SR-C in the diabetic subjects alone was also significant (r = 0.88, P less than 0.0001). In conclusion, our data support the use of U-C as an indirect measure of SR-C and therefore of SR-I.

Topics: Adult; C-Peptide; Diabetes Mellitus; Fasting; Humans; Insulin; Insulin Secretion; Metabolic Clearance Rate; Obesity; Peptides

Blood glucose, plasma insulin and C-peptide concentrations were measured in response to a standard meal in eight Type 2 (non-insulin dependent) diabetic patients before and after treatment with gliclazide for 33 +/- 9 months. Compared with the pre-treatment values, blood glucose levels remained significantly lower (p less than 0.00001), while plasma insulin and C-peptide concentrations remained significantly higher (p less than 0.00001 and p less than 0.001 respectively) throughout the treatment period. In contrast to previous studies, these findings demonstrate that prolonged sulphonylurea treatment produces continued enhancement of B cell secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Gliclazide; Humans; Insulin; Male; Middle Aged; Sulfonylurea Compounds

In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects. The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively. Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.

Topics: Adult; Aged; Arginine; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Insulinoma; Islets of Langerhans; Liver Cirrhosis; Male; Middle Aged; Nephritis; Pancreatic Neoplasms; Peptides; Tolbutamide

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Female; Humans; Insulin; Insulin Antibodies; Male; Middle Aged; Peptides

Residual beta cell function was estimated in 35 young diabetic patients (25 Blacks and 10 Indians) and 22 controls by means of C-peptide assays using glucagon as a provocative agent. The basal C-peptide levels (mean 0,32 +/- 0,23 nmol/l) and the 6-minute post-glucagon levels (mean 0,56 +/- 0,47 nmol/l) were significantly lower in the diabetic patients than in the controls (mean values 0,49 +/- 0,20 nmol/l and 1.24 +/- 0,48 nmol/l respectively). None the less, residual beta cell function, as gauged by the presence of significant C-peptide increments in response to glucagon provocation (mean increase 75% of basal level), was present in most of the patients. The Black patients had significantly lower basal and 6-minute post-glucagon C-peptide levels than the Indian patients.

Topics: Adolescent; B-Lymphocytes; Black or African American; Black People; C-Peptide; Child; Diabetes Mellitus; Female; Glucagon; Humans; India; Male; Peptides; South Africa

Insulin secretion and insulin resistance were examined in seven obese type II diabetics before and after control of plasma glucose levels without weight loss. Control was achieved by regular insulin injection (60-205 U/day in four doses). After 10 days of therapy, plasma insulin and C-peptide responses to oral glucose were significantly improved. Insulin-induced glucose rates, estimated by the glucose clamp technique, averaged 1.08 +/- 0.30 mg/kg. min (mean +/- SEM; n = 7) before treatment and were unchanged (1.08 +/- 0.25) after treatment. These indicate that short term control of plasma glucose improved insulin secretion but not insulin sensitivity. The impaired insulin secretion and insulin sensitivity in type II diabetics appears to be, in part, secondary to metabolic abnormalities associated with hyperglycemia.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Obesity

Topics: Adolescent; Adult; Aged; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Glucagon; Hispanic or Latino; Humans; Islets of Langerhans; Male; Mexico; Middle Aged; Thyroid Gland

A comparative study was carried out on B cell response to alternative intravenous glucagon (1.0 mg) and intravenous glucose (0.33 g per kg body weight) in healthy non-obese persons (c-NOb), healthy obese persons (C-Ob), non-obese non-insulin-dependent diabetics (NIDD-NOb) and obese non-insulin-dependent diabetics (NIDD-Ob). Each group comprised ten subjects. C-peptide (CP immunoassay using antiserum M 1230) and IRI in the serum were measured for each test. After glucose load in B-cell responses were significantly lower in both the diabetic groups than in the normal groups. After glucagon injection there were no significant differences in IRI and CP levels between NIDD-NOb and C-NOb, however, significantly lower levels of serum CP were noted among NIDD-Ob in comparison to C-Ob with a lack of these differences in IRI levels. This phenomenon is well reflected by the molar IRI/CP ratio expressed as a percentage. In the fasting state IRI accounted in C-Ob for 8.8 +/- 3.5 per cent of CP, while in NIDD-Ob for up to 25. +/- 10.4 percent of CP (P = 0.0004). In the latter group of patients, the IRI/CP ratio after glucagon reached the highest values (over 30 per cent) observed in this study. These data suggest the important role in insulin disposal played by the liver in non-insulin-dependent diabetes associated with obesity. Another explanation for these data is that more proinsulin is secreted in this group of patients as compared to other groups.

Topics: C-Peptide; Diabetes Mellitus; Glucagon; Glucose; Humans; Insulin; Obesity; Peptides

A new in vivo test of insulin sensitivity is described. It utilizes closed-loop insulin delivery device (GCIIS, Biostator) capable of infusing glucose and insulin according to preselected algorithms. In euglycemic patients, insulin was infused by GCIIS to maintain euglycemia in the face of challenges with gradually increasing doses on intravenously administered glucose. Under the described experimental conditions, the endogenous insulin release was minimized as evidenced by serum C-peptide levels of less than 2 ng/ml, and thus the peripheral disposal of glucose should have depended entirely on the exogenous insulin. The amount of the insulin infused was considered to be a measure of peripheral insulin sensitivity. The test was applied to normal and non diabetic obese individuals, and to diabetics, both insulin dependent and independent. Significant insulin resistance was demonstrated in the obese and diabetic patients. In two obese females, the test was repeated after a prolonged period of starvation, and showed marked increase in insulin sensitivity. In two poorly controlled insulin dependent diabetics, marked increase in insulin sensitivity was also observed, here following a prolonged period of euglycemia (48 hours). It is concluded that the GCIIS controlled insulin sensitivity test is a simple, reliable test of peripheral insulin sensitivity, most convenient for clinical and experimental studies in vivo.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Infusion Systems; Kinetics; Obesity

To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. PLasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Humans; Hydroxybutyrates; Insulin; Insulin Infusion Systems; Kinetics; Middle Aged

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Glycated Hemoglobin; Humans; Insulin; Peptides

Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Peptides

In non insulin dependent diabetics (N.I.D.D.) of normal body weight, the acute insulin response to glucose is defective while that to pharmacologic agents such as tolbutamide is less impaired. This specific B-cell insensitivity to glucose results from unknown and perhaps multiple mechanisms. Hyperglycemia may be itself aggravate this phenomenon. To test this hypothesis acute insulin release (delta I: sum of increment at 2, 5, 10 min) after intravenous and tolbutamide injection was studied in 5 N.I.D.D. with fasting blood glucose averaging 12.1 mM/I (range 10.7-13.7) before and after 20 hours of glycemic normalization by an artificial pancreas. Intravenous injection of .3 g/k glucose did not elicit an acute insulin or C-peptide response, but following Tolbutamide (20 mg/kg) delta I was 44 +/- 21 microU/ml and delta C-peptide 0.84 +/- 0.37 nM/I. After 20 hr of normoglycemia a response to glucose was apparent (delta I 60 +/- 24 and delta CP 0.86 +/- 26) that to Tolbutamide was unchanged (delta I 58 +/- 26 and delta CP 0.97 +/- 0.27). These results suggest that 20 hr of normoglycemia improve significantly the "glucoreceptor" function of the B-cell in N.I.D.D.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Glucose; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Time Factors; Tolbutamide

The relative contributions of alpha and residual beta cell function and the presence of insulin binding antibodies to indices of glucose control have been assessed in a group of 44 patients with insulin dependent disease of variable duration. Residual beta cell secretion was detected in 18 patients (40%) but no patient receiving insulin for more than five years showed evidence of residual function. Indices of glucose control were significantly better (p less than 0.001) in patients demonstrating residual secretion. In contrast, no relation was found between glucose control and either fasting of post prandial plasma glucagon concentrations. Insulin binding antibodies were detected in all but two patients but did not correlate with either daily insulin dose or glucose control. These results are consistent with the view that residual beta cell function contributes to improved glucose control in the yearly years of insulin dependency but alpha cell function and insulin antibodies do not.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Middle Aged

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Obesity

The increased incidence of severe hypoglycemia reported in young children with diabetes is consistent with a defect in glucagon secretion or a generalized abnormality in islet hormone secretion. To assess pancreatic hormone and gastric inhibitory polypeptide secretion in children with early onset diabetes, 12 children with onset of diabetes prior to the age of 28 months were studied and the data compared to the hormone responses observed in 11 children with LOD, diagnosed after the age of 5 years. Plasma glucose, C-peptide, glucagon, pancreatic polypeptide, and gastric inhibitory peptide concentrations were measured during and following an arginine infusion (500 mg/kg over 60 minutes) and a mixed meal. During arginine infusion, plasma glucose and glucagon increased similarly in both groups and returned to basal concentrations following discontinuation of arginine infusion. In contrast, plasma C-peptide, hPP, and GIP concentrations did not change. Following the mixed meal plasma glucose, hPP, and GIP concentrations increased similarly in the two groups of children, but no change was observed in either plasma glucagon or C-peptide concentrations in either group. These data demonstrate that EOD and LOD are associated with insulin insufficiency alone and that abnormalities in secretion of other pancreatic islet hormone or GIP cannot be implicated in the high incidence of severe hypoglycemia observed in children with EOD.

Topics: Arginine; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Gastric Inhibitory Polypeptide; Glucagon; Humans; Hypoglycemia; Infant; Infusions, Parenteral; Insulin; Islets of Langerhans; Male; Pancreatic Polypeptide; Time Factors

Inasmuch as the elevated levels of substance(s) immunologically cross-reactive with insulin (SICRI) in a diabetic woman with carcinoma of the corpus uteri decreased following the surgical removal of the uterus and ovaries, 80 women with cervical carcinomas of various stages and 70 women with carcinomas of the corpus uteri of various stages were screened for the levels of SICRI and C-peptide. The levels of SICRI in the second, third, and fourth stages of the cancers were elevated (up to six times above the normal levels of immunoreactive insulin) and stage-dependent. The levels of C-peptide, which are related to the insulin-secreting activity of pancreatic beta-cells, were normal and independent of the stage of cancer.

Topics: Adenocarcinoma; Aged; Blood Glucose; C-Peptide; Cross Reactions; Diabetes Complications; Diabetes Mellitus; Female; Humans; Insulin; Neoplasm Staging; Probability; Radioimmunoassay; Uterine Cervical Neoplasms; Uterine Neoplasms

Ninety obese "diabetic" patients, including 55 treated with insulin injection, were characterized by measurement of levels of insulin or connecting peptide of proinsulin (C peptide) induced during oral glucose tolerance testing. After reduction of body weight to ideal values, patients whose peak serum insulin levels were initially 64 microunits/mL or greater had reductions of blood glucose values from 227 +/- 24 to 122 +/- 10 mg/dL (fasting) and from 400 +/- 49 to 160 +/- 11 mg/dL (two hours postprandial); at C-peptide peaks of 6.0 ng/mL or greater, these blood glucose values fell from 244 +/- 30 to 118 +/- 12 mg/mL and from 400 +/- 51 to 160 +/- 16 mg/dL, respectively. Patients with peak values of less than 60 microunits/ml for insulin or less than 6.0 ng/mL for C peptide did not normalize the blood glucose concentration after weight loss. This critical level of insulin secretory reserve separating these groups was similar to that previously reported for avoidance of diabetic retinopathy and neuropathy. These results suggest that levels of insulin or C peptide induced during glucose tolerance testing distinguish between two types of hyperglycemic obesity-insulin-dependent diabetes mellitus and insulin-resistant obesity. Blood glucose levels alone did not identify these groups. Among consecutive hyperglycemic obese patients, 36% achieved normoglycemia by weight loss alone, including 33% of those previously treated with insulin injection.

Topics: Adult; Body Weight; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Peptides

The influence of sulfonylurea on the secretion, disposal and effect of insulin was studied in 9 Type 2 diabetics during 3 one-month courses of treatment with a) chlorpropamide (t1/2 greater than 24 h) once daily, b) glipizide (t1/2 = 2-4 h) once daily, and c) glipizide in divided doses. Food intake by each patient was identical during each period. Blood concentrations of immunoreactive insulin (IRI) and C-peptide (radioimmunoassays), and of glucose (enzymatic assay), chlorpropamide (gas chromatography) and glipizide (high-pressure liquid chromatography) were determined before and after breakfast and lunch on the 4th day of each examination period. All comparisons were intraindividual. Despite the lunch-time dose of glipizide given during the divided dose treatment, once-daily administration of this drug led to higher drug concentrations not only after breakfast but also for the first few hours after lunch. Divided dosage, on the other hand, led to higher concentrations later. In contrast to once-daily dosage, continuous exposure to glipizide was found in most patients. Chlorpropamide gave the most continuous sulfonylurea exposure. The blood glucose levels were inversely related to the concurrent sulfonylurea concentrations; glucose levels after breakfast and lunch were lowest during once-daily glipizide, whereas the fasting level was lowest during chlorpropamide treatment. The IRI response to breakfast was 60%-70% higher during once-daily glipizide than during the other two treatments but the C-peptide responses to breakfast were almost identical. Thus, the greater after-breakfast availability of peripheral insulin appeared to be due to an effect of glipizide on the extrapancreatic disposal of the hormone.

Topics: Aged; Blood Glucose; C-Peptide; Chlorpropamide; Diabetes Mellitus; Female; Glipizide; Half-Life; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Sulfonylurea Compounds

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fasting; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged; Peptides

The study included 75 young diabetics, having a mean age of 13.7 (+/- 3.4) years, and whose diabetes duration was 5.0 (+/- 3.1) years. All of the subjects were insulin dependent, and none had developed insulin resistance. Injections of either conventional or purified insulin were used. The subjects' diets were "spontaneously balanced", and their physical exercise was similar to non-diabetic school-age children. The 75 diabetics were arbitrarily divided into two groups, A and B, according to their average insulin dose/kg, either less than 1 U/kg or greater than 1 U/kg. Groups A and B were comparable according to their age, age of diabetic onset, degree of diabetic control, frequency of retinal complications, proportion of different insulin types, and concentration of beef or pork insulin antibodies. Insulin antibodies were therefore not responsible for any modification in insulin needs. Insulin needs per kg were very significantly correlated to residual secretion of endogenous insulin (r = -0.34; p less than 0.001). They were equally dependent on the duration of diabetes probably because of the progressive beta cell exhaustion. Insulin needs were also weakly negatively correlated to weight, therefore the heaviest diabetics injected an insulin/kg dose relatively less than the lighter diabetics.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetic Retinopathy; Dose-Response Relationship, Drug; Female; Humans; Insulin; Insulin Antibodies; Male; Peptides

The relation between glucose homeostasis and insulin secretion (immunoreactive insulin and C-peptide) was studied in middle-aged males matched for age and body weight. Subjects with mild type II diabetes mellitus were compared to normals and to individuals with impaired glucose tolerance (IGT). In addition, the diabetics were subdivided according to duration, some of the subjects having recently deteriorated from IGT status. In the IGT individuals, there were no indications of a reduction in basal or glucose-induced insulin output. On the contrary, data indicate somewhat higher than normal secretion. Within the type II diabetics, those of short duration were largely similar to normals, whereas diabetes of longer duration was associated with some diminution in indices of B cell secretion. The data support the notion that a deficient insulin output is not a primary pathophysiological event in the development of type II diabetes.

Topics: Age Factors; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Male; Middle Aged; Peptides

The effect of iv tolbutamide on endogenous glucagon levels was measured in nine insulin-dependent diabetic patients chosen because they evidenced no C-peptide response to beta-cell secretagogues. Basal glucagon levels were not suppressed by a sustained tolbutamide infusion; in fact, a slight stimulatory effect was observed at 5, 10, 30, and 45 min. In the absence of detectable insulin secretory capacity and suboptimal insulin replacement, tolbutamide appears to be a stimulus, not a suppressant, of glucagon secretion.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Kinetics; Male; Middle Aged; Tolbutamide

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Child, Preschool; Chromatography; Diabetes Mellitus; Glycated Hemoglobin; Humans

Chemistry, biochemistry and physiology of proinsulin and C-peptide are summarized. A short characterization of the radioimmunological methods for measuring C-peptide and proinsulin follows. The determination of C-peptide and proinsulin which was mainly carried out in serum or plasma essentially improved our knowledge about the function of the beta-cells in the islets of Langerhans in healthy subjects and diabetic patients. The paper reports on the occurrence and the course of C-peptide and proinsulin in healthy subjects and in diabetics of type I and II.

Topics: Adult; Amino Acid Sequence; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Peptides; Proinsulin; Radioimmunoassay

Topics: C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Male; Peptides; Time Factors

The aim of the present study was to further evaluate the significance of circulating platelet aggregates induced by somatostatin in insulin-dependent diabetic subjects. Eight insulin-dependent diabetics and eight normals were infused with somatostatin at increasing doses (250, 500, and 750 microgram/h), each dose for 30 min. In diabetics, somatostatin induced the appearance in blood of platelet aggregates in a dose-dependent fashion, the highest level being observed with the highest dose (750 microgram/h), p less than 0.005). In normals, circulating platelet aggregates were detected only with the infusion of the highest rate of somatostatin (p less than 0.025). This effect of somatostatin was reversible, since it tended to disappear 30 min after the infusion was stopped. In six additional insulin-dependent diabetics, a previous infusion of phentolamine (0.5 mg/min) completely prevented the appearance of platelet aggregates by somatostatin. No significant variation of the aggregation response to both ADP and collagen and the platelet count was seen in both experiments. Somatostatin, as expected, reduced the basal concentration of plasma glucose, glucagon, and C-peptide in both diabetics and normals. On the basis of these results, we suggest that somatostatin has some proaggregating capacity in vivo, probably by interacting with adrenergic mechanisms.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Glucagon; Humans; Male; Middle Aged; Phentolamine; Platelet Aggregation; Platelet Count; Somatostatin

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Peptides; Radioimmunoassay

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Glucagon; Hormones; Humans; Hydroxybutyrates; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Urea

On the basis of results of simultaneous determinations of plasma free insulin and free c-peptide, episodes of hypoglycemia in an insulin-dependent diabetic were attributed to surreptitious self-administration of insulin. Immunoreactive c-peptide values were falsely increased and diagnostically misleading when measured in unextracted plasma. After preliminary removal of antigen/antibody complexes from the plasma by extraction with polyethylene glycol, the c-peptide values, referred to as "free c-peptide," were suppressed. We suggest that insulin antibodies formed complexes with proinsulin-like material in the plasma of this patient, which accounted for most of the c-peptide immunoreactivity in her unextracted plasma. These complexes must be removed if c-peptide measurements are to be accurate.

Topics: Adolescent; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hyperinsulinism; Insulin; Peptides; Radioimmunoassay; Self Medication

Infants with transient neonatal diabetes mellitus are small for gestational age and fail to thrive postnatally unless insulin is administered. We have measured the concentrations of insulin-related growth factors in an infant girl with this condition to learn if deficiencies in one or more of these factors could be responsible for the impaired growth. Cord blood serum radioimmunoassayable insulin and somatomedin C/insulin-like growth factor I (SMC/IGF-I) were low, but insulin-like growth factor II (IGF-II) measured by a specific radioreceptor assay was normal. Insulin therapy begun on the fourth day of life resulted in a prompt increase in weight and a delayed rise in SMC/IFG-I. No significant changes in IGF-II were observed. After 2.5 months, insulin treatment was discontinued. At that time, endogenous insulin secretion was documented by increased urinary C-peptide. Normal growth and SMC/IFG-I levels persisted. We conclude that growth failure in this condition may be related not only to a lack of insulin but also to SMC/IGF-I deficiency. A deficiency in IGF-II is not involved.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Small for Gestational Age; Insulin; Insulin Secretion; Insulin-Like Growth Factor I; Peptides; Somatomedins

Topics: Adult; Automobile Driver Examination; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Legislation, Medical; Male; Peptides

Topics: Adult; Aged; Arginine; Aspirin; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose; Humans; Insulin; Islets of Langerhans; Kinetics; Male; Middle Aged

Topics: Adolescent; Antibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Histocompatibility; Humans; Infant; Islets of Langerhans; Male; Prospective Studies

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Complications; Diabetes Mellitus; Erythrocytes; Female; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Receptor, Insulin; Renal Dialysis

This study examined the feasibility of continuous programmed intraperitoneal insulin infusion to maintain glycemic control in insulin-dependent, "C"-peptide-negative diabetic man over a 5-day period. The insulin was delivered via a transcutaneous ip catheter from a portable, programmable insulin delivery pump. All 10 diabetic subjects received ip insulin during the day and night, and plasma glucose, free insulin, and C-peptide concentrations were evaluated at 16 intervals throughout each 24-h period. Standard American Diabetes Association recommended diets were provided, and the insulin dosage was adjusted for both premeal glycemia and the quantity of calories ingested. All subjects maintained normal daily activities including attendance at work or school but slept in the Clinical Research Center at night. Our results demonstrate that continuous programmed ip insulin infusion can maintain glycemic control in insulin-dependent diabetic man for 5 days. Furthermore, normalization of plasma free insulin profiles can be achieved, with sharp peaks of insulin coincident with the rise in glucose at each meal. We conclude that the peritoneum may be an appropriate insulin delivery site for C-peptide-negative diabetic man.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Food; Humans; Insulin; Male; Peritoneal Cavity

The effect of chlorpropamide on blood glucose, plasma insulin, C-peptide and glucagon levels was studied in 21 patients with insulin-independent diabetes. A metabolic profile of these parameters was obtained throughout a normal day in seven newly-diagnosed diabetic patients (group A), before, and 3 to 8 weeks after treatment with chlorpropamide was established, and in 14 patients on longterm therapy with chlorpropamide (seven taking less than 250 mg. chlorpropamide--group B; seven taking 250-375 mg.--group C), before, and two weeks after withdrawal of the drug. In group A, correction of hyperglycaemia was not accompanied by a significant rise in the mean plasma insulin and C-peptide levels but a fall was observed in the mean plasma pancreatic glucagon concentrations. In groups B and C, withdrawal of chlorpropamide produced no significant change in plasma insulin, C-peptide or glucagon levels, although the mean blood glucose increased. This study supports an extrapancreatic effect of chlorpropamide to lower blood glucose after prolonged administration. In the short-term, it is possible that chlorpropamide may influence the secretion of pancreatic glucagon.

Topics: Adult; Aged; C-Peptide; Chlorpropamide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Kinetics; Male; Middle Aged; Peptides

A compartmental model formed by plasma glucose, proinsulin, insulin, and C-peptide was proposed to allow a quantitative evaluation of the interrelationship among the different components of the system and to obtain a better discrimination between normal and pathologic subjects. In 11 control subjects, in 6 mild diabetics, and in 9 severe diabetics (insulin-dependent), the kinetics of plasma glucose, insulin, and C-peptide after an i.v. injection of glucagon (sampling for about 120 min) were fitted to the model which was solved with digital computing techniques. Since biphasic plasma insulin and C-peptide kinetics were demonstrated in many normals and mild diabetics, the effect of glucagon in the model was represented by a differential plus a proportional effect. The model (formed by 6 compartments and 14 transfer constants) takes into account the fact that insulin and C-peptide derive monomolecularly from proinsulin and that liver inactivates insulin. The values of the parameters obtained were submitted to stepwise discriminant analysis in order to obtain their relative importance in discriminating among the three groups of subjects. With respect to normal subjects, we found in diabetics an increased inflow of glucose into plasma; a decreased effect of glucagon in promoting the proinsulin response; a decreased effect of glucose in promoting the proinsulin response; a decreased glucose utilization; a lower coupling effect of insulin on glucose; and a higher disappearance rate of C-peptide. We observed a lower formation of insulin and C-peptide from proinsulin in severe diabetics.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Humans; Insulin; Kinetics; Male; Middle Aged; Models, Biological; Peptides; Proinsulin

The close anatomical relationships betaeen pancreatic alpha and beta cells makes possible their interaction at a local (paracrine) level. To demonstrate this in vivo, we have compared the acute glucagon response to intravenous arginine in the basal state and after beta cell suppression by infusions of insulin. The plasma glucose concentration was maintained by the glucose clamp technique. In six normal weight nondiabetics, infusion of insulin at 0.2 mU/kg per min (rate 1) raised the mean +/- SEM plasma insulin levels from 10 +/- 3 to 32 +/- 4 mU/liter and at 1 mU/kg per min (rate 2) raised plasma insulin to 84 +/- 8 mU/liter. This resulted in beta cell suppression, as shown by a diminution in the acute insulin response (incremental area under the insulin response curve, 0-10 min): basal = 283 +/- 61, 199 +/- 66 (rate 1) and 143 +/- 48 mU/liter per 10 min (rate 2) and a fall in prestimulus C-peptide from 1.05 +/- 0.17 to 0.66 +/- 0.15 and to 0.44 +/- 0.15 mM/liter (all P less than 0.01). This beta cell suppression was associated with increased glucagon responses to arginine: 573 +/- 75 (basal), 829 +/- 114 (rate 1), and 994 +/- 136 ng/liter per 10 min (rate 2) and increased peak glucagon responses 181 +/- 11 (basal), 214 +/- 16 (rate 1), and 259 +/- 29 ng/liter (rate 2) (all P less than 0.01). In all subjects, there was a proportional change between the rise in he acute glucagon response to arginine and the fall in the prearginine C-peptide level. To demonstrate that augmented glucagon response was due to betw cell suppression, and not to the metabolic effect of infused insulin, similar studies were performed in C-peptide-negative-diabetics. Their acute glucagon response to arginine was inhibited by the insulin infusion: 701 +/- 112 (basal), 427 +/- 33 (rate 1), and 293 +/- 67 ng/liter per 10 min (rate 2) as was their peak glucagon response: 268 +/- 69, 170 +/- 36, and 115 +/- 33 ng/liter (all P less than 0.01). Thus, hyperinsulinemia, within the physiological range achieved by insulin infusion, inhibits beta cell secretion which, via a paracrine mechanism, potentiates glucagon secretion.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Pancreas

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diagnostic Errors; Glycosuria; Humans; Insulin; Insulin Antibodies; Male; Time Factors

10 obese subjects with latent glucose-intolerance we studied before and after a "short term" treatment with an oral antidiabetic drug, phenformina (100 mg/day for 14 days). The parameters we evaluated, were: basal IRI, C-peptide immunoreactive (IRCP), IRCP/IRI ratio, areas elicited by values of IRI after oral glucose tolerance test (OGTT), basal H-Prl, before and after the phenformin (F) treatment. Our data show that F decreases the basal IRI values but not IRCP values, so the IRCP/IRI ratio is significantly higher. No difference is found in the basal H-Prl values.

Topics: Adult; C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Obesity; Phenformin; Prediabetic State; Prolactin

The 'basal' plasma glucose, defined as the stable overnight concentration, has been assessed as an index of diabetes control by comparison with plasma glucose measurements during 24-h profiles in diet-treated maturity-onset diabetic patients and normal subjects. The basal plasma glucose correlated with the total (r=0.98) and incremental (r=0.86) glucose areas, as well as the 24-h M value (r=0.90). In mild diabetes the basal value was more abnormal than the incremental glucose area after meals, since 3 h after meals 'reactive hypoglycaemia' lowered the plasma glucose to less than the basal value. Thus diabetics with a raised basal glucose up to 8 mmol/l can have a normal 3-h post-prandial value. A raised basal plasma glucose provides similar diagnostic information to conventional oral glucose tolerance tests and provides an apposite measure of diabetes control. Diabetics who come up to a clinic, or who exercise whilst fasting, have fasting plasma glucose and insulin concentrations slightly higher than their overnight 'basal' levels, whereas there is little change in normal subjects. This higher 'stressed fasting' plasma glucose needs to be taken into account when assessing fasting plasma glucose values.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Humans; Insulin; Physical Exertion

The purpose of this study was to investigate whether the great differences in metabolic control between labile and stable insulin dependent juvenile diabetics could be explained by differences in residual pancreatic B cell function. Nine labile diabetics, ten stable diabetics on one insulin injection a day and nine stable diabetics on two insulin injections a day were investigated during a 24-h period during which they maintained their usual diet and insulin therapy. Serum C-peptide concentrations were measured after removal of proinsulin bound to insulin antibodies. The labile diabetics did not show any significant change in C-peptide concentrations despite great fluctuations in plasma glucose concentrations. In six patients with stable diabetes, C-peptide responses after the main meals could be demonstrated and there was a significant correlation between the concentrations of C-peptide and glucose (r = 0.85, p less than 0.001). The other stable patients, having the same mean plasma glucose concentration and mean amplitude of glycaemic excursions, did not show any C-peptide response. It is concluded that persistent insulin secretion is not a prerequisite for metabolic stability. Severe lability, however, seems to occur only in the absence of residual insulin secretion.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Islets of Langerhans

In 14 insulin dependent diabetics past their initial remission period B-cell function was evaluated using a test meal before and after 1 week of strict blood glucose control, and again 3 weeks later when the patients were outpatients on conventional therapy. Eight patients with fasting C-peptide above 0.07 nmol/l improved their B-cell function significantly (p Less Than 0.05) during the period of strict blood glucose control. However, the improvement was of short duration and was absent 3 weeks later in most patients. Six patients with fasting C-peptide below or equal to 0.07 nmol/l had no significant improvement in B-cell function during the period of strict control. The study shows that B-cell function and degree of blood glucose control are related in patients with fasting C-peptide above 0.07 nmol/l, and that B-cell function can change within days.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Male

The effects of Ca2+ and calcitonin infusions on circulating glucagon, glucose, C-peptide, Ca2+, and calcitonin were investigated in hyper-glucagonaemic insulin-dependent diabetics. In 14 insulin-deprived diabetics and 12 healthy volunteers 2h infusions of saline (0.154 mol/1), Ca2+ (0.375 mmol/kg body weight), and calcitonin (4.5 IU/kg body weight) were performed. There were no significant changes during saline infusion. In the diabetics, Ca2+ infusions induced a rise of plasma Ca2+ up to 3.2 +/- 0.1 mmol/1 and a fall of circulating glucagon (-26.4 +/- 5.7%; p less than 0.001) and glucose (-23.3 +/- 3.6%; p less than 0.05). Plasma calcitonin rose to twice basal values (p less than 0.025). During calcitonin infusions plasma Ca2+ decreased slightly to 2.1 +/- 0.2 mmol/1; a fall was found in both glucose (-24.4 +/- 4.0%; p less than 0.05) and circulating glucagon (-22.5 +/- 4.3%; p less than 0.001). Two groups of 6 healthy volunteers were subjected to saline and Ca2+, or to Ca2+ and calcitonin infusions. Both Ca2+ and calcitonin infusions induced a fall of serum insulin (-30.1 +/- 6.6%; p less than 0.05). Calcitonin depressed circulating glucagon by -18.6 +/- 4.4% (p less than 0.025), whereas during Ca2+ infusions glucagon decreased only by -6.5 +/- 1.9% (p greater than 0.1). We conclude from our results that an increase of circulating calcitonin induced by Ca2+ infusions or by exogenous calcitonin administration appears to depress elevated circulating glucagon and glucose in insulin-dependent diabetics.

Topics: Adult; Blood Glucose; C-Peptide; Calcitonin; Calcium; Diabetes Mellitus; Glucagon; Humans; Insulin

Fourteen insulin-treated diabetics were submitted to an arginine infusion test performed with either 11.7 or 5.85 mg kg-1 min-1 arginine monohydrochloride infused during 40 min with or without previous oral administration of a low (75 + 50 mg) or a high (75 mg + 3 mg/kg) dose of indomethacin. Blood glucose, plasma non-esterified fatty acids, insulin, C-peptide and glucagon were determined at regular intervals before, during and after the arginine infusion. These parameters were totally unaffected by the two doses of indomethacin both in the basal state and during the arginine infusions at the two loads tested. Eight subjects had a basal C-peptide level above 0.07 pmol/ml and a mean (+/- SEM) maximal rise of 0.21 +/- 0.04 pmol/ml during the arginine infusion, whereas the remaining six patients had virtually zero values throughout the tests. The arginine-induced plasma glucagon rise was similar for the two rates of arginine infusion; the sum of the increments in plasma glucagon averaged 877 +/- 120 and 647 +/- 92 pg/ml (p greater than 0.1) for the high and low rates of arginine infusion, respectively. The magnitude of the blood glucose rise appeared independent of the amount of arginine infused. Confirming previous reports, we found that the blood glucose rise after arginine was three to four times higher in subjects without C-peptide than in subjects with C-peptide. The mean glucagon response did not differ significantly between subjects with or without C-peptide. Thus, residual B cell function determines the magnitude of the blood glucose rise but not the glucagon response after intravenous arginine.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glucagon; Humans; Indomethacin; Insulin; Islets of Langerhans; Male; Middle Aged; Peptides

In order to discriminate between insulin-dependent and non-insulin-dependent patients, serum C-peptide concentration was determined using antiserum M1230 in the fasting state and 6 min after an i.v. injection of 1 mg glucagon in 215 patients treated with insulin and 53 treated with diet and oral antidiabetics. A patient was considered well controlled without insulin when fasting blood glucose was below 8 mmol/l and when glucosuria was absent. After re-evaluation of therapy in hospital it was found that the majority of patients with a post-stimulatory serum C-peptide concentration above 0.60 pmol/ml appeared to have non-insulin-dependent diabetes mellitus. When fasting C-peptide was used, a great overlap was found between the two treatment groups. During evaluation of therapy in hospital, 6 previously insulin-treated patients could be well treated with diet and tablets and 6 diet- and tablet-treated patients required insulin. The glucagon test seems to be of value in the outpatient clinic to discriminate non-insulin-dependent from insulin-dependent patients.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Fasting; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Peptides

Twenty patients were changed from a single daily injection of beef insulin (a mixture of soluble and protamine zinc insulin) to two daily injections (mixtures of soluble and isophane insulins). This was associated with a reduction, one month later, in the concentration of glycosylated haemoglobin (HbA1) and in the degree of late evening glycosuria. A reduction was shown 6 months later in antibody binding of beef and pork insulin by serum. Subsequent conversion to a twice daily regime of highly purified pork insulin was not associated with further improvement in diabetic control, but was associated after 1 month with a reduction in daily insulin dose, and after 5 months with a further reduction in antibody binding of beef and pork insulin by serum. Patients failing to show a C-peptide response to intravenous glucagon had a fall in HbA1 after conversion from a once to a twice daily insulin regime, which correlated inversely with insulin antibody binding estimated at the beginning of the study.

Topics: Adolescent; Adult; Aged; Animals; C-Peptide; Cattle; Diabetes Mellitus; Drug Administration Schedule; Female; Follow-Up Studies; Hemoglobin A; Humans; Insulin; Insulin Antibodies; Male; Middle Aged; Species Specificity; Swine

Acarbose, an alpha-glucosidase inhibitor, delays starch digestion and inhibits intestinal sucrase and maltase activity. Twenty-eight insulin dependent diabetics were given Acarbose (3 x 100 mg daily) over a two month period, preceded and followed by a two month placebo period. Acarbose reduced post-breakfast and post-dinner blood glucose values by 25% (p less than 0.001) and 24% (p less than 0.05) respectively. It also significantly reduced mean daily blood glucose by 18% (p less than 0.05) and mean amplitude of glycaemic excursions from 8.0 +/- 0.6 to 5.5 +/- 0.4 mmol/l (p less than 0.0005). Weight did not change significantly. Daily caloric and carbohydrate intake remained constant throughout the study while insulin requirements decreased slightly but significantly. Out of the 28 patients, 18 had absent while ten had slight residual B cell function as assessed by plasma C-peptide measurements. Treatment with Acarbose did not significantly affect residual B cell function. The beneficial effect of Acarbose on blood glucose control was seen in patients both with and without residual B cell secretion. The major side-effect was flatulence which was never severe enough to interrupt treatment, but led to a 50% reduction of the dose in one patient. It is concluded that Acarbose represents a useful additional means of improving metabolic control in insulin dependent diabetics.

Topics: Acarbose; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucosidases; Glycoside Hydrolase Inhibitors; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Oligosaccharides; Time Factors; Trisaccharides

Endogenous insulin secretion was quantified in patients with maturity-onset diabetes (MOD) whose diabetes was controllable solely by caloric regulation as primary therapy. Insulin was used adjunctively only and persistent attempts were made to withdraw it as weight loss occurred in response to diet. Insulin secretory capacity was measured by C-peptide response during a standard 100-g oral glucose tolerance test in 24 patients who achieved normalization of plasma glucose level as a result of dietary therapy alone. Summed C-peptide levels for the diet-controlled diabetic patients was 7.8 +/- 0.7 pmol/mL as compared with 6.1 +/- 0.45 pmol/mL for a group of ten normal-weight, nondiabetic volunteers.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Peptides

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Glucagon; Humans; Hydroxybutyrates; Insulin; Oxidation-Reduction; Physical Exertion

Topics: C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Humans; Insulin; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetic Retinopathy; Female; HLA Antigens; Humans; Insulin; Insulin Antibodies; Insulin Secretion; Male; Middle Aged

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Food; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Peptides; Secretory Rate; Terbutaline

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Food; Humans; Insulin; Male; Middle Aged; Peptides

In an attempt to examine the influence of sulfonylurea on the secretion, disposition and effect of insulin, 9 diabetic patients were studied during three one-month medications with (a) chlorpropamide (t1/2 greater than 24 h) once daily, (b) glipizide (t1/2 2-4 h) once daily, and (c) glipizide in divided dosage. The food intake of each patient was identical during each examination period. Blood concentrations of C-peptide, insulin, glucose, and drugs were determined before and after breakfast and lunch on the 4th day of each examination period. As expected, once-daily administration of glipizide led to higher after-breakfast concentrations of the drug than when the dose was divided. However, the C-peptide changes following breakfast were similar both during these two treatments and also during chlorpropamide, indicating that the amounts of insulin released from the pancreas were equivalent. In spite of this, glipizide once daily yielded 60-70% more insulin in systemic blood following breakfast than did the two other treatments. Reasonably, this signifies that the hepatic extraction of insulin was reduced during once-daily glipizide, allowing more insulin to reach systemic circulation. In addition, this was found to promote a more effective utilization of glucose following breakfast. Following lunch, the C-peptide release, the plasma insulin increase and the blood glucose reduction were greater when glipizide was given in divided dosage than when once-daily glipizide or chlorpropamide was employed. This occurred even though the after-lunch concentration of glipizide in systemic blood was lower rather than higher during divided than during once-daily administration. This supports the notion that the effect of orally administered sulfonylurea is determined not only by its concentration in systemic blood but also by its gastroenterohepatic appearance. Glipizide may offer greater therapeutic flexibility than chlorpropamide, but further studies are required to define the optimum choice and use of sulfonylureas.

Topics: Aged; Blood Glucose; C-Peptide; Chlorpropamide; Diabetes Mellitus; Female; Food; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Peptides; Sulfonylurea Compounds

Plasma immunoreactive insulin and peptide were measured in the basal and glucose-stimulated state in middle-age males. Normals were compared with individuals with mild to moderate glucose intolerance. Ths results demonstrate the value of C-peptide measurements in the assessment of "true" insulin secretion and suggest that a reduced hepatic insulin extraction is a feature of the glucose intolerant state.

Topics: C-Peptide; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Liver; Male; Middle Aged; Peptides

The selective beta 2-adrenergic agonist salbutamol increases plasma glucose concentration and the rate of lipolysis when infused in pregnant diabetic women. The aim of the present study was twofold: (a) to focus on the actions of salbutamol on lipid and carbohydrate metabolism in insulin-dependent diabetics: and (b) to investigate possible interferences of acetylsalicylic acid (ASA) with the metabolic responses to i.v. salbutamol. The results obtained during salbutamol infusion (5 microgram/min) in 6 insulin-dependent diabetic subjects demonstrated that this drug caused sustained increases in plasma glucose, free fatty acid and beta-hydroxybutyrate concentrations, as well as a small and transient rise of plasma glucagon. No change in plasma C-peptide concentration occurred during salbutamol. A concurrent infusion of lysine acetylsalicylate reduced the increase in free fatty acids by half, blunted the weak glucagon response but enhanced the rise in plasma glucose following salbutamol administration. The present data show that salbutamol exerts a potent hyperglycemic, lipolytic and ketogenic effect in insulin-dependent diabetics. We suggest that this beta-adrenergic agent should be used cautiously in human diabetes mellitus.

Topics: Adult; Albuterol; Aspirin; Blood Glucose; C-Peptide; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glucagon; Humans; Hydroxybutyrates; Kinetics; Male; Middle Aged

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Peptides; Reagent Kits, Diagnostic

Topics: C-Peptide; Diabetes Mellitus; Humans; Liver Diseases; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Humans; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: Adult; C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Humans; Male; Middle Aged; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: C-Peptide; Diabetes Mellitus; Humans; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Plasma C-peptide levels were measured both in the fasting state and in response to a standard breakfast in 37 Type 1 (insulin dependent) diabetics with severe proliferative retinopathy, 20 Type 1 diabetics without complications and 13 non-diabetic subjects. The two diabetic groups were matched for age and duration of diabetes. Seventeen out of 37 subjects with diabetic complications had detectable C-peptide compared with three out of 20 in the group without complications (p less than 0.05). There was a significant correlation between fasting C-peptide levels when present and the increment in C-peptide (r = 0.89, p less than 0.0001). There was no correlation between C-peptide levels and the fasting blood glucose or HbA1. No evidence was found to support the hypothesis that in long-term diabetics, sufficient beta-cell function may persist which measurably influences diabetic control and prevents the development of microvascular complications.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Fasting; Female; Hemoglobin A; Humans; Kinetics; Male; Middle Aged; Peptides

Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo later after resumption of exogenous insulin therapy. In both patients, carbohydrate metabolism was nearly normal during the period of graft function. Two patients died of infectious complications between 1 and 2 mo after transplantation. The main hazard of pancreas transplantation relates to the immunosuppression necessary to prevent rejection, setting the stage for infectious complications. Technically, pancreas transplantation is a feasible and efficient procedure, and, if better methods are developed for preventing rejection, it should be applicable to patients prone to develop secondary complications of diabetes.

Topics: Adult; Amylases; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Kidney Transplantation; Lipase; Male; Pancreas Transplantation; Transplantation, Homologous

A synthetic human C-peptide analogue has been used as a common standard for the comparison of insulin C-peptide measurements in seven assay systems in six laboratories. Even in terms of this common standard there was statistically significant numerical heterogeneity between laboratories for estimates of the C-peptide content of the same plasma samples. However, the consistency in ranking order of estimates of C-peptide in the plasma samples between laboratories suggests that laboratories are in most cases measuring at least similar immunoreactive constituents and that a reference plasma might prove useful in comparing results between laboratories. Until a more suitable reference material is available, the synthetic analogue, 64 formyllysine C-peptide, in ampoules coded 76/561, will be made available for research purposes.

Topics: Adenoma, Islet Cell; C-Peptide; Diabetes Mellitus; Humans; Pancreatic Neoplasms; Peptides; Proinsulin; Quality Control; Radioimmunoassay

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatitis; Transplantation, Autologous; Transplantation, Homologous

Residual insulin secretion, reflected by the presence of C-peptide in serum and urine, has been demonstrated in 5 of 10 insulin-requiring diabetics of less than 10 years' duration tested. The C-peptide response, in the C-peptide secretors, showed a significant increase in both serum and urine after 4 weeks' treatment with 15 mg glibenclamide daily in addition to their usual insulin regime although no beneficial effects in metabolic control were detected. It is suggested that glibenclamide might be a useful adjunct to insulin therapy in insulin-requiring diabetics who still secrete C-peptide.

Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus; Female; Glyburide; Humans; Insulin; Insulin Secretion; Male

A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction. Lethal effects in rats prevented investigation of RH-787's diabetogenicity in vivo; however, studies in isolated rat islets confirmed a direct inhibitory effect, which was prevented by concomitant incubation with nicotinamide, suggesting a mechanism of action similar to that of streptozotocin. We detected islet cell-surface antibodies in two of four patients studied. These findings indicate that this nongenetic, acquired form of insulinopenic diabetes, which has persisted in the surviving patients for up to 3 yr, presents a unique opportunity to test in man the concept that hyperglycemia and the accompanying metabolic consequences of insulinopenia can induced diabetic microangiopathy in the absence of genetic predisposition.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetic Ketoacidosis; Diabetic Neuropathies; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Phenylurea Compounds; Tolbutamide

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans Transplantation; Male; Membranes, Artificial; Middle Aged; Surgical Procedures, Operative

Human fetal pancreas preserved in culture was used as a donor organ in a 45-yr-old man with diabetes of 14-yr duration complicated by severe retinopathy and nephropathy. Renal failure had been successfully treated by a cadaveric renal transplant 2 yr earlier. Six fetal pancreases, obtained within 30 min of delivery after prostaglandin-induced abortion at 14--20 wk of gestation, were minced and placed in tissue culture for 3 h at the earliest and 15 days at the longest duration. The cultures were harvested 2--3 h before transplantation. Approximately 3 ml of tissue was infused into a right portal vein branch. Azathioprine was continued at 2 mg/kg and prednisolone increased from 10 mg to 100 mg/day on the day of transplantation and gradually reduced to 25 mg/day. Only two doses of antilymphocytic globulin were given because of a severe reaction. During the 40 days since transplantation, insulin requirements have not changed, but C-peptide has appeared in the urine, suggesting function of the transplanted tissue.

Topics: C-Peptide; Diabetes Mellitus; Female; Fetus; Humans; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Organ Culture Techniques; Pancreas Transplantation; Portal Vein; Pregnancy; Transplantation, Homologous

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Peptides; Radioimmunoassay

Topics: Adult; C-Peptide; Cushing Syndrome; Diabetes Mellitus; Fasting; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Male; Middle Aged; Peptides; Time Factors

Residual insulin secretion and islet-cell antibodies were studied in 399 insulin-dependent diabetics with age at onset of between 10--19.9 years (248 patients) or 30--39.9 years (151 patients). We found the prevalence of islet-cell antibodies to be independent of residual beta-cell function as measured by serum C-peptide and age at onset. The cause and role of the persistence of islet-cell antibodies in insulin-dependent diabetics remain obscure.

Topics: Adolescent; Adult; Age Factors; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Islets of Langerhans

The artificial endocrine pancreas (AEP) can normalize glycemia at rest and with meals. To determine whether insulin, glucagon, and amino acid profiles are also normalized, nine diabetics on subcutaneous insulin (S/C) and AEP control were compared to ten normal controls (NC). Glycemia was monitored continuously over 10 hr during which meals were consumed. Insulin infusion rate, and the levels of immunoreactive insulin (IRI) (in NC), free insulin (in S/C and AEP), C-peptide, glucagon, and amino acids are reported. Glycemia in AEP started at somewhat higher levels than in NC, but with breakfast and thereafter, it was identical. In S/C, hyperglycemia prevailed throughout, with no systematic change in free IRI. In AEP, both basal and peak free insulin levels, measured in four patients, were significantly higher than in NC. C-peptide values were significantly lower in diabetics and did not change with meals. Basal glucagon values were not different in the three groups and changes with meals were of small magnitude. Branched chain amino acids were higher in S/C and did not increase as in NC. In AEP, levels were lower than NC after the first two meals. Similarly, lysine and threonine were lower in AEP than in NC at the same times. Alanine, though similar at the onset, was lower 2 hr postbreakfast and higher 2 hrs postsupper in AEP and S/C compared to NC. These studies demonstrate that glycemic control with AEP is accompanied by hyperinsulinemia, which could account for the amino acid responses and the small alterations in immunoreactive glucagon (IRG) patterns. Further refinement is needed to obtain full normalization of metabolic profiles.

Topics: Adolescent; Adult; Amino Acids; Artificial Organs; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Food; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Middle Aged

In a random one day study beta-cell function was evaluated in 210 insulin treated diabetics by the serum C-peptide concentration 6 min after iv injection of 1 mg of glucagon. Sixty-five patients (31%) had residual beta-cell function. As a group these patients were characterized by having a higher age at onset of diabetes (P less than 0.01), a shorter duration of disease (P less than 0.01) and by receiving a smaller dose of insulin (P less than 0.01). However, their quality of metabolic control did not differ from the patients without beta-cell function. Although the concentrations of post-stimulatory C-peptide correlated inversely with both the 24-hour glycosuria (P less than 0.01) and the fasting blood glucose concentrations (P less than 0.02), only a subgroup with C-peptide concentrations exceeding 0.30 pmol/ml showed a definitely better degree of metabolic control than those without beta-cell function. As this subgroup also received the smallest dose of insulin these observations suggest that maintenance of beta-cell function above this level facilitates good metabolic control. Evidence is presented suggesting that measurements of the 24-hour glycosuria undertaken in a diabetes clinic create a too optimistic impression of the quality of metabolic control during every day life.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Insulin; Islets of Langerhans; Male; Middle Aged

Glucose and hormone profiles, including plasma levels of glucagon, GH, total insulin, free immunoreactive and biologically active insulin were determined by hourly sampling in two groups of insulin dependent diabetics. The five patients in Group I were recently diagnosed and still had residual beta-cell function. The other six in Group II had disease of longer duration, had developed insulin antibodies, and were non-secretors of C-peptide. All patients were studied while receiving their usual maintenance doses of Semilente monocomponent insulin (Novo). Daily insulin requirements were 25.6 +/- 4 U in Group I and 52.2 +/- 7 U in Group II. The glucose profiles were similar in the periprandial periods but over the whole 24-hour period control was more unstable in the patients of Group II and during the period 2400-0200 h plasma glucose fell to low levels (minimum plasma glucose 1.5-3.0 mmol/l). Free insulin levels rose to peak levels over a similar time course but then fell more slowly in the Group II subjects. These patients had higher free, biologically active insulin and lower glucagon levels which were coincident in time with the early morning hypoglycaemia. These observations suggest that raised free insulin levels in the setting of an impaired counter-regulatory glucagon response are one of the factors contributing to glucose instability in long-standing diabetics.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Growth Hormone; Humans; Insulin; Insulin Antibodies; Peptides

Plasma C-peptide and serum insulin antibody levels were determined in 5 diabetic patients undergoing vascularized pancreatic transplantation. The grafts functioned well at first and exogenous insulin could be withdrawn, but one to 7 weeks later the grafts were rejected. After the transplantation there was an increase in the fasting plasma C-peptide level, and B-cell stimulation with glucose or glucagon evoked a C-peptide response. Healing of ischaemic damage was reflected in an increase in the C-peptide level. During graft rejection the C-peptide level fell. Measurement of plasma C-peptide levels provides a direct index of the B-cell function of the pancreatic graft. After transplantation the insulin antibody level fell exponentially, with an apparent half life of 10-11 days, whereas the level of total IgG was variable. The results indicate that formation of insulin antibodies ceases immediately on removal of the immunogenic stimulus, that is, on withdrawal of xenogeneic insulin.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin Antibodies; Male; Pancreas Transplantation; Peptides; Transplantation, Homologous

The discussion about a connection between diabetes and psoriasis is picked up again. Serum-values of glucose, insulin and C-peptide after intravenous glucose-load and of glucose and C-peptide after intravenous insulin-load were tested. The level of insulin and C-peptide after i. v. glucose-load was found higher in psoriasis-patients (hyperinsulinism). Considering earlier investigations and new results in diabetes-research (incretin concept), a connection between the two diseases must be denied. The carbohydratemetabolism-deviation in psoriasis could be declared by an enteropathy.

Topics: C-Peptide; Diabetes Mellitus; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Psoriasis

A radioimmunoassay for C-peptide utilizing synthetic C-peptide as an antigen and tyrosylated synthetic C-peptide for iodination was evaluated for its clinical use. Mean fasting C-peptide levels in 24 normal subjects was 2.6 +/- 0.8 ng/ml. During the oral glucose tolerance test, baseline C-peptide in five normal subjects was 1.5 +/- 0.8 ng/ml, and at 60 min was 5.6 +/- 1.6 ng/ml. For two insulin-dependent diabetic patients, diagnoses of factitious hypoglycemia were documented on the basis of simultaneous free insulin and C-peptide determinations. Sera from 24 insulin-dependent diabetics were analyzed for free and total immunoreactive C-peptide and insulin levels. For 20% of juvenile and 64% of maturity-onset diabetics, the presence of proinsulin-like material bound to insulin antibodies was demonstrated by measurement in unextracted serum. This accounted for 20% to 100% of total C-peptide immunoreactivity in these patients. Simple polyethylene glycol precipitation of immune complexes and the measurement of free immunoreactive C-peptide in the supernatant demonstrated subnormal levels (less than 0.5 ng/ml) in all juvenile diabetics and normal levels (1.8 +/- 1.3 ng/ml) in 70% of maturity-onset diabetics.

Topics: Adolescent; Adult; Antigen-Antibody Complex; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Peptides; Radioimmunoassay

Haemoglobin AIc concentrations were measured in 102 insulin-treated diabetic outpatients. Only 19% had Hb AIc levels below three standard deviations above the normal mean value (5.23 +/- 0.05%). There were no correlations between Hb AIc levels, random C-peptide immunoreactivity or age. A significant correlation (r = 0.49; p < 0.001) was, however, observed between HbAIc and random plasma glucose levels. The mean random plasma glucose value was normal (89 +/- 18 mg/100 ml; 5 +/- 1 mmol/l) in the patients on insulin three times a day who had received short acting insulin 160 +/- 6 min before the sampling. --A significant inverse correlation was found (r = -0.26; p < 0.01) between the number of daily insulin injections and the HbAIc concentration. --These results suggest that the use of multiple daily insulin injections improves diabetic control. It should however be emphasised that the patients receiving multiple insulin injections were younger than those on the single injection regime and had lower plasma insulin antibody titres, different social and psychological status and a shorter duration of the disease.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Drug Administration Schedule; Fasting; Female; Glycosides; Hemoglobin A; Humans; Insulin; Male; Middle Aged; Socioeconomic Factors

After the iv injection of 2 micrograms isoproterenol, peripheral plasma insulin and C-peptide concentrations were measured in 16 nonobese normal subjects and 53 maturity-onset diabetic subjects. Basal insulin (P < 0.01) and C-peptide (P < 0.05) levels were increased in obese diabetic subjects compared to nonobese normal subjects. Isoproterenol-stimulated insulin (P < 0.01) and C-peptide (P < 0.05) increments were increased in obese diabetic subjects compared to nonobese diabetic subjects. Hepatic insulin extraction, measured by comparing the ratios of insulin increment to C-peptide increment after isoproterenol injection, was decreased in both nonobese and obese diabetics compared to normals (P < 0.05). No significant differences in the ratios were found between nonobese and obese diabetics or between patients on diet or sulfonylurea therapy. Age, sex, duration of disease, familial predisposition to diabetes, and diabetic retinopathy did not influence the ratios. Isoproterenol-stimulated C-peptide increments (P < 0.05) and fasting blood glucose levels (P < 0.05) were decreased in diabetics showing decreased hepatic insulin extraction compared to diabetics with normal hepatic insulin extraction. Isoproterenol-stimulated insulin increments in diabetics showing decreased hepatic insulin extraction were higher than in normals (P < 0.05). These studies indicate that hepatic insulin extraction decreases in nonobese and obese diabetic subjects. It might be postulated that the lesser amount of secreted insulin is able to show biological activities more efficiently in diabetics with decreased hepatic insulin extraction.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Secretion; Isoproterenol; Kinetics; Middle Aged; Obesity; Peptides; Reference Values; Sulfonylurea Compounds

Topics: Adult; C-Peptide; Diabetes Mellitus; Glucose; Humans; Islets of Langerhans; Middle Aged; Peptides; Proinsulin; Radioimmunoassay

Eleven newly diagnosed insulin dependent patients were studied before and during the first 16 h after start of insulin treatment. All the patients were found to have significant amounts of C-peptide in plasma indicating residual insulin secretion. The fall in blood glucose after start of insulin therapy was followed by a parallel decrease in C-peptide (R = 0.99, P < 0.01) suggesting that the beta-cells may respond to variation in blood glucose. Eight of the patients were studied 1, 4, 7, 14, 90 and 180 days after start of insulin therapy. During the first 90 days of treatment an increasing maximal C-peptide concentration was found after a standard breakfast test meal. Two thirds of this improvement i beta-cell function was found after the initial 14 days with an average increase in maximal C-peptide of 260 per cent. The sensitivity to glucose improved.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Time Factors

Topics: Adolescent; Adult; C-Peptide; Child; Diabetes Mellitus; Female; Glucagon; Glucose; Humans; Injections, Intravenous; Insulin; Male; Middle Aged; Obesity; Peptides; Stimulation, Chemical

Three groups of ten similar obese children were infused with one of three protocols. Protocol I glucose only (1.15 mM/min/m2). protocol II, glucose, insulin (42 mM/min/m2). Protocol III, glucose insulin, propanolol (0.04 mg/min/m2) adrenalin (3 micrograms/min/m2). Eighteen newly diagnosed diabetic children without acidosis received glucose according to protocol II. Thirteen normal adults (controls) received glucose infusion according to protocol I. Protocols I and II were well tolerated and gave consistent results but Protocol III was not well tolerated and did not give interpretable results. In obese children steady state blood glucose levels are significantly higher than in controls but this difference was only moderate (8.8 + 0.7 mM, against 6.6 +/- 0.4 mM for protocol I). There was no difference in insulin levels. In diabetic children the steady state was more rarely obtained after a 120 min infusion and blood glucose levels were higher than in the controls or in obese children.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Epinephrine; Glucose; Humans; Insulin; Insulin Resistance; Obesity; Propranolol

Late results were obtained from the follow up of 48 patients with chronic pancreatitis, who underwent partial duodenopancreatectomy. We measured the rest function of the remaining B-cells after resection by daily glucose profile, i.v.-gtt, measurements of the glucagon stimulated C-peptide-output and the amount of C-peptide in the 24-h-urine. In 9% of the cases the operation induced diabetes in addition to the already existing 31%. 3/4 of the nondiabetics showed a latent diabetic metabolism (K value < 1.0). The cause of this, as shown by the C-peptide-analysis, was the loss of the endocrine functional reserve following pancreas resection because of chronic pancreatitis. Therapeutically great differences resulted in reaching and equilibrium of serum glucose in the pancreas resected insulin-dependent patients, because they were dependent on carbohydrates for energy. The tendency to hypoglycaemia represented an additional endangerment.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Duodenum; Follow-Up Studies; Humans; Islets of Langerhans; Pancreatectomy; Pancreatitis; Postoperative Complications

The interaction between variation in insulin absorption and beta-cell function was studied as well as the possible relation between subcutaneous blood flow through the region of injection and the variability in insulin absorption. The results indicate that the dose of insulin, the type of insulin preparation and the local blood flow influence the insulin absorption. Residual endogenous insulin secretion, governed by the blood glucose values, serves as a modulator.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Islets of Langerhans; Skin

Topics: Adolescent; Adult; Arginine; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Female; Humans; Insulin; Islets of Langerhans; Male; Pancreatic Function Tests; Peptides; Stimulation, Chemical; Time Factors

In this paper, we have compared the results obtained for hemoglobin A1c and C-peptide concentrations, was not convenient for the diagnosis of anomalies in the regulation of carbohydrate metabolism in obesity or in latent diabetes. Nevertheless, hemoglobin A1c allowed us to check carbohydrate metabolism and to discriminate diabetes treated by oral therapy from insulin dependent diabetes; in these latter cases, hemoglobin A1c concentration varied inversely as C-peptide concentration as it was shown by the method of factor analysis in particular "principal components analysis". In the control of insulin dependent diabetes in a remission, hemoglobin A1c allowed assessment of the regulation of carbohydrate metabolism after suppression of insulin therapy. Thus, hemoglobin A1c is an index of the adaptation of insulin secretion in anomalies of carbohydrate metabolism.

Topics: C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus; Glycosides; Hemoglobin A; Humans; Hypoglycemic Agents; Insulin; Obesity; Peptides

To test the possibility that insulitis might play an etiological role in the pathogenesis of insulin dependent diabetes, functions of 3 kinds of islet constituting cells (A, B and PP cells) were estimated by quantifying secretory responses of glucagon-, C-peptide-and pancreatic polypeptide-producing cells to hyperglycemia and hypoglycemia. In insulin dependent diabetes, all 3 hormonal responses were severely impaired to the same extent. On the other hand, 3 islet cell functions were uniformly but less severely impaired in insulin independent diabetics without a diabetic family history. These results suggest that A, B, and PP cells of islet of Langerhans are evenly destroyed in parallel fashion at least in insulin dependent diabetes and in some insulin independent diabetes, suggesting insulitis as a possible cause of these types of diabetes.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Glucose; Humans; Insulin; Islets of Langerhans; Pancreatic Polypeptide

Topics: C-Peptide; Cross Reactions; Diabetes Mellitus; Female; Humans; Immune Sera; Insulin Antibodies; Peptides; Pregnancy; Pregnancy in Diabetics; Proinsulin; Radioimmunoassay

Topics: C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Humans; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

The presence or absence of chlorpropamide-alcohol flushing (CPAF) was not correlated with the classification of diabetes. Five out of twelve patients with juvenile-onset diabetes (JOD) flushed and three out of four patients with maturity-onset diabetes in young people (MODY) did not flush. Consequently, CPAF cannot be used for individual genetic counseling in diabetes mellitus.

Topics: Adolescent; Adult; Blushing; C-Peptide; Child; Chlorpropamide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Ethanol; Genetic Counseling; Humans; Middle Aged; Risk; Tolbutamide

Topics: C-Peptide; Diabetes Mellitus; Evaluation Studies as Topic; Humans; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Nine of ten non-obese non-ketotic diabetics attending Port Moresby General Hospital had detectable C-peptide in plasma. All had received insulin for at least two months at the time of study. It is concluded that many non-obese non-ketotic young diabetics in Papua New Guinea retain pancreatic insulin secretion and so resemble the maturity onset diabetics of "Western" countries.

Topics: Adolescent; Adult; Body Weight; C-Peptide; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Insulin; Insulin Secretion; Male; New Guinea

The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg, t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419-0.33 g/kg intravenously). In the majority of "stable" diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In "unstable" diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in "stable" diabetics (p less than 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially "unstable" diabetics in need of strict observation, which would minimize the risks of bad metabolic control.

Topics: Adult; Arginine; C-Peptide; Diabetes Mellitus; Fasting; Glyburide; Humans; Insulin; Middle Aged; Peptides; Protein Binding; Radioimmunoassay

Topics: Adult; C-Peptide; Diabetes Mellitus; Encephalomyocarditis virus; HLA Antigens; Humans; Insulin

The contents of insulin and C-peptide extractable with acid alcohol from the tail of the pancreas and insulinoma were investigated, using gel filtration in seven nondiabetics including two patients with insulinoma and eight diabetics. The gel filtration patterns of both C-peptide and insulin in pancreatic extract were fairly stable even after the pancreas had been left for 14 hrs in the room temperature. In nondiabetics except cases of insulinoma the content of insulin in pancreas ranged from 1.42 to 4.56 U per gram and that of C-peptide from 8.76 to 25.63 microgram per gram wet pancreas. The proportion of proinsulinlike components (PLC) ranged from 0.01 to 2.04% of insulin plus PLC. In diabetics insulin content was low and ranged from 0 to 1.68 U per gram and that of C-peptide from 0 to 14.48 microgram per gram wet pancreas. In insulinoma, both insulin and C-peptide increased and PLC occupied 5.48 and 5.96%, respectively.

Topics: Adenoma, Islet Cell; Adult; Aged; C-Peptide; Chromatography, Gel; Diabetes Mellitus; Female; Humans; Insulin; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Peptides; Proinsulin

Beta cell function has been studied by measurement of C-peptide responses to intravenous glucagon in 11 diabetics with advanced complications and compared with nine long-term diabetics without complications. The majority had no C-peptide responses, but there was evidence of beta cell function in one patient from each group. These observations suggest that some factor other than continuing beta cell function is involved in the complications of insulin-requiring diabetics.

Topics: Adult; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Peptides

In 10 insulin dependent maturity onset diabetics we found elevated basal C-Peptide levels (4.78 +/- 0.5 ng/ml. Normal range 1.1--3.6 ng/ml), which could be suppressed by insulin injection to the same extent as in sulfonylurea treated diabetics could be demonstrated. C-Peptide immunoreactivity in these patients therefore seems to be newly secreted rather than accumulated material. Since adrenalectomized patients could be suppressed in the same way, it is likely, that catecholamines are not the major factor in the mechanism of suppression. Therefore only decrease of bloodsugar levels seems to be accountable for the decrease of C-Petide levels. High C-Petide levels in insulin dependent maturity onset diabetics which cannot be stimulated but suppressed may be explained by a loss of glucoreceptor molecules.

Topics: Adrenalectomy; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Islets of Langerhans; Peptides; Sulfonylurea Compounds

To clarify further the etiology of the carbohydrate intolerance in idiopathic hemochromatosis, we investigated the glucose, insulin, C-peptide, and glucagon responses to arginine (0.5 g/kg) infused during 30 min in lean normal subjects; in insulin-requiring subjects with hemochromatosis, genetic diabetes, and total pancreatectomy; and in nondiabetic cirrhotic subjects without portosystemic shunting. Serum insulin, C-peptide, and glucagon responses (30K antibody) were determined by RIA, and glucose level was determined by a glucose oxidase technique. Hemochromatotic and genetic diabetic subjects had similar basal glucose (157 +/- 25 vs. 168 +/- 40 mg/dl) and C-peptide (0.73 +/- 0.42 vs. 0.65 +/- 0.22 ng/ml) values, with subnormal C-peptide peak responses to stimulation (1.05 +/- 0.38 and 1.40 +/- 0.83 vs. 3.95 +/- 0.4 ng/ml in normals; P less than 0.05). No glucagon or C-peptide response to arginine was seen in any pancreatectomized subject. Similar but excessive glucagon levels were present in hemochromatosis, diabetes, and cirrhosis under basal conditions (166 +/- 24, 232 +/- 111, and 263 +/- 116 vs. 76 +/- 15 pg/ml; P less than 0.05) and after arginine stimulation (782 +/- 80, 834 +/- 123, and 902 +/- 275 vs. 489 +/- 81 pg/ml; P less than 0.05) when compared with normals. The excessive glucagon levels found in hemochromatosis, diabetes mellitus, and cirrhosis contrast to the absent response in pancreatectomized subjects and indicate that generalized islet cell destruction is not the major factor in diabetic hemochromatotic subjects.

Topics: Adult; Aged; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Hemochromatosis; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreatectomy

Topics: Adult; Artificial Organs; Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Eating; Feedback; Humans; Hydrocortisone; Infusions, Parenteral; Insulin; Islets of Langerhans; Male; Middle Aged; Monitoring, Physiologic

Topics: Artificial Organs; Blood Glucose; C-Peptide; Diabetes Mellitus; Eating; Feedback; Glucagon; Growth Hormone; Homeostasis; Humans; Hydrocortisone; Infusions, Parenteral; Insulin; Islets of Langerhans

Using a Biostator glucose-controlled insulin infusion system to monitor blood glucose during surgery, we have shown that both nondiabetic and diabetic patients have a tendency towards hyperglycemia during surgery. This appears to be due to suppression of endogenous insulin secretion as measured by serum C-peptide levels. Some diabetic patients maintained relatively normal glucose values during surgery when infused with saline alone and not given glucose or insulin, but 2 of 5 were not well controlled by this means. Hyperglycemia in both diabetic and non-diabetic patients was related to the rate of infusion of exogenous glucose. The biostator glucose-controlled insulin infusion system could be used in feedback mode as an apparently safe and effective means of controlling blood glucose during surgery on diabetic patients.

Topics: Artificial Organs; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Hydrocortisone; Hyperglycemia; Infusions, Parenteral; Insulin; Islets of Langerhans; Surgical Procedures, Operative

Five insulin-dependent diabetics with poor metabolic control were examined at the beginning and after a three-day application of artificial endocrine pancreas (AEP). Pancreatic alpha cell function evaluated by arginine infusion (0.5 g/Kg b.w. over 30 minutes) showed no significant differences between the beginning and during artificial beta cell aplication, but the increment in plasma glucagon level over basal values observed in both tests appeared significantly higher at 30 and 60 min in comparison with a control group. Growth hormone response to arginine infusion was clearly reduced in the second test. C-peptide concentration appeared very low in basal conditions and during arginine infusion; no improvement was observed after three days of AEP application. Urinary excretion of norepinephrine markedly increased at the beginning of the study, reversed almost to normal during AEP treatment, while minor changes were observed in urinary excretion of epinephrine. The Concentration of glycosylated hemoglobin, markedly higher than normally before the connection with AEP, showed a slight but significant decrease during glucose-controlled insulin infusion. Finally, 2,3-diphosphoglycerate was normal and no modifications were observed in the course of the study.

Topics: Arginine; Artificial Organs; Blood Glucose; C-Peptide; Catecholamines; Diabetes Mellitus; Diphosphoglyceric Acids; Erythrocytes; Glucagon; Glycosides; Growth Hormone; Hemoglobin A; Infusions, Parenteral; Insulin; Islets of Langerhans

Topics: Adult; Arginine; Aspirin; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Peptides

To elucidate pathogenetic factors of bone mineral loss in diabetes mellitus, bone mineral content (BMC), glucose and calcium homeostasis were evaluated in a cross-sectionsl study of 215 insulin-treated diabetics. BMC declined 10% during the first 5 years of diabetes. This coincided with cessation of insulin secretion, deterioration of metabolic control and raising urinary calcium excretion rates of calcium and phosphorus. BMC was inversely correlated to fasting blood glucose (P less than 0.02), to glycosuria (P less than 0.02) and to insulin requirement (P less than 0.002), and positively to the glucagon-stimulated serum C-peptide levels (P less than 0.005). Urinary excretion rates of calcium and phosphorus correlated positively with the degree of hyperglycaemia (P less than 0.001) and glycosuria (P less than 0.001). The skeletal calcium loss corresponded to the excess of urinary excretion during the phase of BMC reduction. There was no evidence of secondary hyperparathyroidism. The relationship between bone loss and disturbed glucose homeostasis indicates that diabetic bone loss is secondary to the metabolic abnormalities, possibly acting directly on bone.

Topics: Adolescent; Adult; Aged; Blood Glucose; Bone and Bones; C-Peptide; Calcium; Child; Creatinine; Diabetes Complications; Diabetes Mellitus; Female; Homeostasis; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Minerals; Parathyroid Hormone; Phosphorus; Time Factors

An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose +/- SEM: 185 +/- 16 mg/dl) and, to a greater degree, diabetics (247 +/- 36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p less than 0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128 +/- 21 mg/dl) as normal subjects receiving saline (110 +/- 7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Glucose; Growth Hormone; Humans; Hydrocortisone; Insulin; Monitoring, Physiologic; Prolactin; Surgical Procedures, Operative

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.

Topics: Adolescent; Adult; Antigens; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Humans; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Obesity; Peptides

Normal and mildly diabetic subjects each have their own "set" of basal plasma glucose and insulin concentrations. Diabetic patients have raised basal plasma glucose, with low-normal basal plasma C-peptide concentrations. Restoring normal glucose levels in mild diabetes by an insulin infusion further reduces the C-peptide concentration, but both the plasma glucose and the C-peptide return to their "set" level when the insulin is withdrawn. These results accord with the action of beta cells and liver in a negative feedback loop that maintains basal plasma glucose and insulin concentrations.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Insulin; Middle Aged

We measured circulating hemoglobin A1 (HbA1) and fasting plasma C-peptide concentrations in 100 diabetic patients. Pancreatic insulin reserve showed a negative correlation with HbA1 concentrations in nonobese, insulin-treated patients but not in obese patients, whether they were treated with insulin, oral agent, or diet alone. Patients with fasting C-peptide concentrations above 0.1 pmol/ml had significantly better metabolic control than did those with lower values. Anti-insulin antibodies were measured in 37 patients. There was no correlation between metabolic control and the affinity constants or binding capacities of these antibodies.

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Glycosides; Hemoglobin A; Humans; Insulin; Insulin Antibodies; Middle Aged; Obesity; Peptides

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Peptides; Radioimmunoassay

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fasting; Humans; Immunoassay; Peptides

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Insulin; Male

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Insulin; Obesity; Peptides; Prediabetic State

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetes Mellitus; Hemoglobins; Humans; Middle Aged; Motor Neurons; Neural Conduction; Peptides

The 24-hour profiles of blood metabolites, serum free and total insulin, and C-peptide were measured in 16 insulin dependent diabetics, and then analysed in order to compare the effects of the presence or absence of residual endogenous insulin secretion and the presence of good or bad diabetic control as judged by the levels of blood glucose or total ketone bodies. Retention of endogenous insulin secretion, responsive to meals, and changes in the level of blood glucose and serum free insulin, were detected in nine patients, its presence having important effects in maintaining metabolic regulation closer towards normal. Despite the fact that apparently well controlled diabetics were selected for the study, the diurnal changes of the levels of blood metabolites, serum free and total insulin and their interrelationships were all grossly abnormal. The levels of both the blood total ketone bodies and the blood glucose were found to be a poor guide to the presence or absence of other metabolic abnormalities of diabetes. High levels of blood total ketone bodies appeared to have a protein sparing effect.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Female; Humans; Insulin; Insulin Secretion; Ketone Bodies; Male; Middle Aged; Peptides

Topics: Autoantibodies; C-Peptide; Diabetes Mellitus; Genes, MHC Class II; Humans; Insulin Antibodies; Islets of Langerhans

Although it is generally believed that insulin secretion is minimal or absent in juvenile-onset diabetes, we have found appreciable levels of C-peptide at the time of onset in 12 patients, 4 to 16 years old (9.3 +/- 4.2). Ten of them had ketonuria but none severe ketoacidosis. All entered a remission period. Most of the patients had near normal C-peptide levels during the remission, and their beta cells had the capacity to respond to a breakfast stimulation with increased insulin secretion. C-peptide and proinsulin were also determined in 98 juvenile diabetics with age at onset of 1 to 16 years (6.8 +/- 3.9) and a duration of diabetes between two and 17 years (6.7 +/- 3.4). Many were found to have persisting beta-cell function, which seems to be of importance for ensuring stability in metabolic control. Although little is known about factors that may slow or reverse the process leading to beta-cell failure, our results suggest that early detection and intensive treatment of diabetes before severe metabolic disturbances have occurred may help preserve beta-cell function.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fasting; Humans; Infant; Insulin; Islets of Langerhans; Ketone Bodies; Kinetics

Maturity-onset diabetic patients usually have raised overnight-fasting plasma glucose levels associated with "normal" basal plasma insulin levels. The basal hyperglycemia is proportional to the degree of insulin deficiency. Basal insulin or C-peptide levels become subnormal if normal fasting plasma glucose levels are attained with insulin. Basal hyperglycemia is probably a compensatory response to maintain near-normal basal insulin levels. A logical therapy of maturity-onset diabetes is to produce basal normoglycemia by means of a constant basal insulin supplement, which can be provided by ultralente insulin. The reduced insulin response of diabetics to intravenous glucose is slightly increased when basal normoglycemia is established, suggesting that the high plasma glucose levels compromise beta cell function. The insulin response to meals in a mild diabetic is not affected by mild hyperglycemia but can be depleted if gross hyperglycemia occurs. Maintenance of normoglycemia then allows beta cell "recovery". In mild diabetics (c. less than 9 mmol per liter basal plasma glucose), chlorpropamide sufficiently stimulates beta cell secretion so that basal normoglycemia can be produced. The C-peptide response to meals is improved, whereas comparable reduction of the plasma glucose with insulin does not alter the meal response. Thus basal normoglycemia can be produced by "resting" beta cells with a basal insulin supplement or by stimulating them with sulfonylurea therapy.

Topics: Blood Glucose; C-Peptide; Chlorpropamide; Circadian Rhythm; Diabetes Mellitus; Humans; Insulin; Islets of Langerhans

The influence of the age at onset as well as the duration of disease on the prevalence of residual beta-cell function was studied in insulin-dependent diabetic patients. Two hundred and sixty-seven patients presented at an early age (10-19.9 years) and 158 patients had a late onset (30-39.9 years of age). beta-cell function was evaluated by measuring serum C-peptide immunoreactivity. Fifty-six patients (21.0 per cent) in the early-onset group and 64 (40.5 per cent) in the late-onset group had residual beta-cell function. The prevalence of residual beta-cell function was almost 100 per cent during the first two years of disease and was lower thereafter in diabetics with early onset. About 15 per cent of all patients with a duration between 15 and 35 years had residual beta-cell secretory function.

Topics: Adolescent; Adult; Age Factors; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Insulin; Islets of Langerhans; Radioimmunoassay

Topics: Adolescent; Adult; Arginine; C-Peptide; Diabetes Mellitus; Female; Humans; Infusions, Parenteral; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Peptides

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucose; Glyburide; Humans; Injections, Intravenous; Insulin; Islets of Langerhans; Male; Middle Aged; Peptides; Tablets

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Glyburide; Humans; Insulin; Male; Middle Aged; Peptides; Radioimmunoassay

Sixteen adult-onset diabetics, who were thought by current criteria to be well controlled on diet alone, had substantially elevated overnight, basal plasma glucose concentrations. Chlorpropamide had a sufficiently prolonged stimulatory effect on the beta cells such that normal basal plasma glucose levels were obtained in 13 patients. Both basal plasma C-peptide levels and the C-peptide response to meals became normal, with improved postprandial glycemia. Diurnal plasma triglyceride levels were reduced. Plasma growth hormone levels were normal both before and after therapy. When diet alone is insufficient to maintain basal normoglycemia in mild diabetes, chlorporpamide is as effective as basal insulin supplements in producing normal basal plasma glucose levels.

Topics: Blood Glucose; C-Peptide; Capillary Fragility; Chlorpropamide; Circadian Rhythm; Depression, Chemical; Diabetes Mellitus; Growth Hormone; Humans; Hydroxybutyrates; Insulin, Long-Acting; Lactates; Obesity; Physical Exertion; Triglycerides

Two groups of 8 diabetics, similar in many aspects, who required high (greater than or equal to 128 units) or low (less than or equal to 32 units) total daily insulin dosage were compared during a 24 hour period. C-peptide secretion was detected in all but one of the low dose group, but only in two of the high dose group. No significant differences in serum free and total insulin concentrations were detected and the patterns of blood metabolites were also similar, apart from higher blood glycerol concentrations in the low dose group. No significant differences in the binding characteristics of the antiinsulin antibodies were detected.

Topics: C-Peptide; Circadian Rhythm; Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Insulin; Insulin Antibodies

The relative significance of residual beta-cell secretory activity and human insulin antibodies in determining diabetic stability has been examined in 35 diabetic subjects. The response of plasma C-peptide immunoreactivity following 50 g oral glucose has been used as an index of beta-cell function. Glucose-stimulated C-peptide secretion was observed in 58% of stable diabetics, but in no labile diabetics. When present, C-peptide secretion following a glucose load in diabetics was of smaller amplitude and slower in onset, but more prolonged than in normal subjects. In secretors, stability of diabetes was significantly correlated with the magnitude of the C-peptide response. As a group, labile diabetics had lower insulin antibody levels than stable patients, but stability and antibody levels were not correlated in individual patients. In non-secretors there was no difference in antibody levels between the stable and labile groups. Neither the equilibrium binding affinities nor the dissociation rate constants differed significantly for antibodies from stable and labile diabetics. Thus stability of diabetes depends upon residual beta-cell secretory activity, but not on the concentration or binding characteristics of insulin antibodies.

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Antibodies; Middle Aged; Peptides

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Peptides; Proinsulin; Radioimmunoassay

Measurement of serum and urinary C-peptide has been shown to be of value in several conditions other than diabetes mellitus. It is particularly useful because it can distinguish endogenous beta cell secretion from exogenously administered insulin and because circulating insulin-binding antibodies do not interfere with its measurement. Because the liver removes little, if any, C-peptide, peripheral blood values may more accurately reflect beta cell secretion than do peripheral insulin levels. Clinically, serum C-peptide has been most useful in diagnosing hypoglycemic disorders. Diagnosis of insulinomas is facilitated in both diabetic and nondiabetic patients, and surreptitious insulin injection is readily detected. In studies of insulin regulation, circulating C-peptide has been used to demonstrate suppression of endogenous insulin secretion by exogenous insulin. Peripheral insulin and C-peptide levels have been compared in studies of the role of the liver in states of altered insulin homeostasis. Because of its higher urinary clearance, determination of urinary C-peptide is preferable to urinary insulin measurement in situations where frequent blood sampling is impossible or difficult to accomplish.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Humans; Hypoglycemia; Male; Middle Aged; Peptides; Radioimmunoassay

The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject. The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the single-dose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3). These results indicate that the beta-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.

Topics: Adult; C-Peptide; Chromatography, Gel; Diabetes Mellitus; Humans; Infusions, Parenteral; Injections, Intravenous; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Peptides

Topics: C-Peptide; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Hemoglobins; Humans

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy. Many patients who are thought to be controlled by diet alone continue to have high plasma-glucose levels. As the rise in the basal plasma glucose concentration is the predominant glucose abnormality of diabetes, treatment should be aimed primarily at producing basal normoglycaemia. 18 mild, maturity onset diabetics have been treated with a basal insulin supplement provided by single daily injections of insulin zinc suspension (crystalline) 'Ultralente'. Overnight basal normoglycaemia has been obtained with markedly reduced plasma-glucose levels during the day. Plama-triglyceride levels have become normal in most patients. The required insulin dose need not be determined empirically, but can be calculated from the basal plasma-glucose level and the degree of obesity. There is minimum risk of hypoglycaemia, and rigid dietary restriction is unnecessary. As mild diabetics are prone to complications, treatment with basal insulin supplements may be beneficial when diet alone fails to produce basal normoglycaemia.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Diet, Diabetic; Follow-Up Studies; Humans; Injections, Subcutaneous; Insulin, Long-Acting; Middle Aged; Obesity; Triglycerides

Proinsulin is converted to insulin and C-peptide in the pancreatic in the pancreatic beta cells: the latter two peptides are secreted in equimolar concentrations. Thus, measurements of serum C-peptide provide a means of assessing pancreatic beta cell function in addition to that of insulin. This technique has proved particularly useful in insulin treated diabetic patients in whom the development of circulating insulin antibodies interferes with the radioimmunoassay of the hormone. The C-peptide assay has also been used to facilitate the diagnosis of various hypoglycemic conditions, including islet cell tumors and factitious injection of insulin. The extraction of C-peptide in the urine reflects average serum values over a period of time and urine C-peptide measurements are especially useful in children or individuals in whom repeated blood sampling is difficult.

Topics: Adenoma, Islet Cell; C-Peptide; Diabetes Mellitus; Humans; Hypoglycemia; Insulin Antibodies; Islets of Langerhans; Pancreas; Pancreatic Neoplasms; Peptides; Proinsulin

Topics: Adolescent; Adult; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin Antibodies; Proinsulin; Radioimmunoassay

Pancreatic beta-cell secretory activity was measured in 17 patients with insulin-dependent diabetes mellitus of less than 19 months' duration and in 10 nondiabetic subjects by means of the peripheral plasma C-peptide response to 1 mg. of glucagon I.V. The C-peptide response to a meal was also measured in the diabetic patients. Residual beta-cell function was present in all the diabetic patients as indicated by significant amounts of C-peptide in plasma. Significant increases in C-peptide were observed in 16 after glucagon stimulation and in 15 after the meal. Both absolute and relative increase in C-peptide were reduced in the diabetic patients. The increase in C-peptide was correlated to the fasting C-peptide concentration both after glucagon (r=0.86, p less than 0.001) and after the meal (r=0.66, p less than 0.01). The responses to the meal and to glucagon were correlated (r=0.77, p less than 0.005), indicating a high predictive value of the glucagon test as to how the beta-cells will respond during normal daily life.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Fasting; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Peptides

In 83 insulin-treated diabetics the influence of the duration of insulin treatment on the prevalence of residual insulin secretion was examined by determining the plasma C-peptide concentration before and after intravenous injection of 1 mg of glucagon. In 64 patients, plasma C-etide concentration was also determined before and after a standard meal. There was a good correlation between the C-peptide response to glucagon and to the meal (r = 0.67; p less than 0.0001) suggesting that the glucagon test will predict the B-cell response during everyday life. The predictive value of a positive glucagon test was 84% and of a negative test 100%. A preserved, but reduced, B-cell function was demonstrable in 36 of 83 patients. Residual B-cell function was most frequent in the patients with the shortest duration of diabetes. The metabolic importance of endogenous insulin was demonstrated by the significantly lower insulin requirement in the patients with residual B-cell function.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Glucagon; Humans; Insulin; Islets of Langerhans; Peptides; Time Factors

"Essential labile diabetes" is an insulin-dependent diabetes, in the course of which irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias alternate. In spite of careful treatment with insulin, diet and suitable hygienic measures, this form of diabetes cannot be influenced. Fortunately, it seldom occurs, not more frequently than in 1 to 2% of diabetics. Various attempts have been made to explain the pathogenesis of this form of the disease. The most probable explanation is that there is an almost complete exhaustion of insulin secretion. This hypothesis is based on the extremely low level of the C peptide below 0.60 ng/ml, whereas in non-labile insulin-dependent diabetics the C peptide amounts to more than 2.2 ng/ml

Topics: Activities of Daily Living; Adult; Arginine; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Diagnosis, Differential; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Secretion; Male; Middle Aged

Topics: Animals; C-Peptide; Diabetes Mellitus; Dogs; Humans; Peptides

Topics: C-Peptide; Diabetes Mellitus; Humans; Peptides

Topics: C-Peptide; Diabetes Mellitus; Humans; Obesity; Peptides; Radioimmunoassay

Diurnal variation of blood sugar, C-peptide immunoreactivity (CPR), free insulin and total insulin were measured in 10 insulin requiring diabetics after obtaining adequate control of diabetes with commercial lente insulin treatment. Following these tests, insulin treatment were changed to monocomponent insulin (MC-insulin) from commercial lente insulin treatment in all subjects and the same tests were performed at 7th day of MC-insulin treatment. Diurnal variations of blood sugar in both groups were not changed significantly. Also changes in CPR of both groups were nearly same magnitude and endogenous insulin secretion in these insulin treated diabetics were suggested except a case of juvenile diabetic subject. However personal variation were great in diabetics with high antibody titer, diurnal variations of total extractable insulin in both groups were quite comparable. And mean diurnal changes in free insulin were resemble to that of CPR. All of these data suggested that clinical effects of MC-insulin and commercial insulin treatment on insulin requiring diabetics were comparable except insulin antibody or proinsulinspecific antibody production.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Circadian Rhythm; Diabetes Mellitus; Drug Evaluation; Female; Humans; Insulin; Insulin, Long-Acting; Male; Middle Aged

Topics: Adult; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Lactates; Male; Peptides

Topics: Adult; Aged; C-Peptide; Diabetes Mellitus; Female; Humans; Insulin; Male; Middle Aged; Peptides; Proinsulin

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Peptides; Syndrome

Serum levels of free and total insulin as well as total C-peptide immunoreactivity (C-peptide and proinsulin) and C- peptide were measured in insulin-treated diabetics with circulating insulin antibodies by the addition of polyethylene glycol (PEG) before and after acidification. PEG resulted in complete precipitation of insulin antibodies from serum and made it possible to measure free insulin in the supernatant. Incubation of serum at 37 degrees C. for two hours before addition of PEG resulted in values for free insulin that probably resembled the in-vivo levels most closely. The same method could also be used to remove proinsulin bound to circulating insulin antibodies and permitted the measurement of C-peptide in the supernatant. Clinical studies using this approach indicate that combined measurements of serum free and total insulin and C-peptide provide information that is helpful in understanding the contribution of endogenous and exogenous insulin to the course and metabolic control of insulin-requiring diabetic patients.

Topics: Antibodies; C-Peptide; Centrifugation; Chemical Precipitation; Chromatography, Gel; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Iodine Radioisotopes; Peptides; Polyethylene Glycols; Pregnancy; Pregnancy in Diabetics; Proinsulin; Temperature

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.

Topics: Adult; Antigens; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose; Growth Hormone; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Sodium Chloride

A 45-year-old, non-obese female patient with no previous history of insulin administration was found to have extreme insulin resistance and abnormally high plasma immunoreactive insulin in the absence of anti-insulin antibodies in the serum. Clinically, there was no ketonuria. The patient also had evidence of Sjogren's syndrome with several immunologic features including hypergammaglobulinemia, positive antinuclear antibodies, accelerated erythrocyte sedimentation rate and leukopenia. Plasma pancreatic glucagon and C-peptide were elevated, but other endocrinologic abnormalties were not present. In this patient the insulin resistance appeared to be due to anti-insulin receptor antibodies which could be detected even in 1:500 dilution of serum. Immunosuppressive therapy with prednisolone and cyclophosphamide resulted in a decreased level of serum gamma globulin and a concomitant decrease of blood glucose level. After immunosuppressive therapy for eight months, the diabetic syndrome disappeared completely and anti-receptor antibodies in the serum were no longer detectable. Furthermore, insulin sensitivity returned to normal. However, the patient's glucose tolerance deteriorated after the temporary termination of cyclophosphamide treatment and the lowering of prednisolone dosage.

Topics: Autoantibodies; C-Peptide; Cyclophosphamide; Diabetes Complications; Diabetes Mellitus; Female; Glucagon; Humans; Immunosuppressive Agents; Insulin; Insulin Antibodies; Insulin Resistance; Middle Aged; Prednisolone; Receptor, Insulin; Sjogren's Syndrome

It is one of the characteristic features in diabetes mellitus that insulin response to glucose is low. Nine low insulin responders with normal glucose tolerance in whom prediabetes mellitus should be suspected were found to be included in 104 apparently healthy subjects (9%). A 100 g glucose tolerance test (GTT) was performed in nine apparently healthy subjects with a low insulin response and 11 healthy subjects with a normal insulin response. A 50 g GTT was performed in 15 normal subjects, 20 subdiabetics, 38 chemical diabetics and 17 mild diabetics. In all subjects C-peptide during GTT was estimated by the double antibody systems using a synthetic human C-peptide. Though C-peptide secretion from the beta cell of the pancreas seems to keep pace with insulin secretion, the peak of C-peptide was delayed in its appearance in the circulating blood, as compared with that of insulin. The pattern of plasma C-peptide during GTT in diabetics was identical with that of insulin. In the low insulin responders C-peptide response to glucose was observed to be lower like that of insulin than in the normal insulin responders. However, a molar ratio of C-peptide to insulin at 30 min during GTT in the former was higher than that in the latter.

Topics: C-Peptide; Diabetes Mellitus; Dose-Response Relationship, Drug; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Pancreas; Peptides; Prediabetic State; Time Factors

Fasting C-peptide levels and those after tolbutamide or glucose stimulation were measured in normal subjects. In patients with various hypo- or hyper-functions of the endocrine pancreas, C-peptide levels were compared with the corresponding insulin levels. In insulin-dependent maturity-onset diabetics there were both normal and elevated serum C-peptide levels. In juvenile diabetics and patients with total duodenopancreatectomy there was no measureable C-peptide. It is concluded that the half-life of C-peptide is three times that of insulin.

Topics: C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose; Half-Life; Humans; Insulin; Pancreatectomy; Peptides; Tolbutamide

Topics: C-Peptide; Cross Reactions; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Peptides

Seventeen insulin dependent diabetics were studied after two to four weeks of insulin treatment in a situation approximating to their normal daily life. Some endogenous insulin secretion, assessed by plasma C-peptide determinations, was present in all. Plasma C-peptide concentration was positively correlated with the blood glucose concentration and increased after breakfast, lunch and dinner (p less than 0.01); both peak values and relative increases were lower than those observed in normal subjects (p less than 0.01). The highest insulin secretory capacity was found in subjects with the least unstable blood glucose concentration (r=0.57, p less than 0.03), and these patients required the smallest insulin doses (r=0.54, P less than 0.04). These findings demonstrate the metabolic importance of a preserved B-cell function.

Topics: Adolescent; Adult; Antigens; Blood Glucose; C-Peptide; Diabetes Mellitus; Dose-Response Relationship, Drug; Eating; Female; Humans; Insulin; Male; Middle Aged; Pancreas

Topics: Adult; Aged; Arginine; Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Glucose Tolerance Test; Humans; In Vitro Techniques; Insulin; Insulin Antibodies; Insulin Secretion; Middle Aged; Pancreas

Topics: C-Peptide; Diabetes Mellitus; Humans; Insulin; Proinsulin; Radioimmunoassay; Reference Values

A scheme is advanced whereby plasma-lipoproteins form an integrated controlled pathway for storage of energy as triglyceride. The importance of insulin within this system is indicated and the consequence of possible errors considered. Changes secondary to organ disease are found to fit within the proposed pathway. Although many refinements remain to be added, this hypothesis seems to form a plausible framework within which lipoprotein abnormality and the underlying condition may be better understood and thereby treated.

Topics: Apolipoproteins; C-Peptide; Cholesterol; Chylomicrons; Diabetes Mellitus; Energy Metabolism; Humans; Hypolipoproteinemias; Insulin; Kidney Diseases; Lecithin Cholesterol Acyltransferase Deficiency; Lipoprotein Lipase; Lipoproteins; Lipoproteins, VLDL; Phosphatidylcholine-Sterol O-Acyltransferase; Triglycerides

Topics: Adenoma, Islet Cell; Adult; Aged; C-Peptide; Child; Diabetes Mellitus; Glucose Tolerance Test; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptides

Topics: Adenoma, Islet Cell; C-Peptide; Diabetes Mellitus; Humans; Insulin; Peptides

Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (+/- 0.4) ng/ml, corresponding to 60.4 X 10(-11) Mol/l. The molar concentration is about five-fold as compared to IMI (immuno-measurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1-2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucose-glibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.

Topics: C-Peptide; Chromatography, Gel; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose; Glyburide; Humans; Insulin; Pancreatic Hormones; Peptides

Topics: Administration, Oral; Blood Glucose; C-Peptide; Diabetes Mellitus; Glyburide; Humans; Insulin; Peptides

A double-antibody radioimmunoassay method, using synthetic human connecting peptide as an immunizing antigen and standard, was evaluated for clinical assay of blood and urine samples. Normal fasting blood connecting peptide immunoreacivity (CPR) was 2.45 +/- 0.96 ng/ml, increasing promptly after a 50 g oral glucose load, but somewhat slower than insulin. Molar concentration of CPR exceeded that of insulin. CPR responses to glucose were subnormal in diabetics, very low in juvenile-type cases, and often poor in patients on insulin treatment. Fasting CPR levels were elevated in patients on corticosteroid treatment and with uraemia. A patient with insulin "auto-antibody" had high serum CPR. A considerable amount of CPR appeared in urine. Normal daily excretion of CPR was 1.52 +/- 0.55 mug/kg or 55.1 +/- 18.2 ng/mg creatinine. Urine CPR was very low in juvenile-type diabetics, and elevated in patients on corticosteroid treatment. The results confirm that blood and urine CPR are useful measures of the endocrine pancreatic function.

Topics: Antigen-Antibody Reactions; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Humans; Insulin; Peptides; Radioimmunoassay

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Glucagon; Humans; Insulin