c-peptide and Kidney-Failure--Chronic

Topics: Animals; C-Peptide; Calcitriol; Clomiphene; Dihydroxycholecalciferols; Female; Follicle Stimulating Hormone; Glomerular Filtration Rate; Glucagon; Gonadotropin-Releasing Hormone; Hormones; Humans; Insulin; Kidney; Kidney Failure, Chronic; Luteinizing Hormone; Male; Metabolic Clearance Rate; Mineralocorticoids; Parathyroid Hormone; Proinsulin; Prolactin; Sexual Dysfunction, Physiological; Thyroid Hormones; Uremia

Recent work from our laboratory on the mechanism of polypeptide hormone handling by the normal kidney and the pathogenesis of altered hormonal metabolism in renal failure is reviewed. The kidney extracts substantial amounts of low - and medium - molecular weight polypeptide hormones from the renal circulation by a process which probably involves both glomerular filtration plus luminal reabsorption and direct peritubular uptake, although the relative contribution of the two mechanisms under physiologic conditions is not known. The bulk of the extracted hormone is catabolized in the renal parenchyma since urinary excretion is negligible. Renal catabolism contributes an important fraction of the total metabolic clearance of polypeptide hormones, which accounts in part for their increased circulating levels in renal failure. Since certain hormones are heterogenous and a large proportion of their plasma immunoreactivity may consist of components of uncertain biologic activity, simple correlations between circulating hormone levels and endocrine abnormalities in uremia are hazardous.

Topics: Animals; Antigens; C-Peptide; Erythropoietin; Glucagon; Gonadotropins, Pituitary; Humans; Insulin; Kidney; Kidney Failure, Chronic; Luteinizing Hormone; Metabolic Clearance Rate; Molecular Weight; Pancreatic Hormones; Proinsulin; Prolactin; Uremia

Eight patients with end stage renal disease (ESRD) on chronic hemodialysis (CHD) treatment were supplemented with 1 g L-carnitine intravenously (i.v.) after each dialysis session for one month. A Tolbutamide test was done and blood sugar (BS), serum C-peptide (CP) were measured at 0, 20 and 60 minutes, as well as the plasma L-carnitine level before and after treatment. Delta CP and the area under CP curve were ascertained. After L-carnitine application delta CP was significantly increased (1.33 +/- 0.63 vs. 2.24 +/- 1.0 nmol/L; p<0.05) and also the area of the stimulated secretion under the CP curve (14.93 +/- 11.11 vs. 36.88 +/- 25.36 nmol/L x 60 min.; p<0.05). The fasting BS-level was significantly lower after the treatment--3.85 +/- 0.43 vs. 4.76 +/- 1.02 mmol/L; p<0.05 and plasma L-carnitine level significantly increased (72.8 +/- 43.2 vs. 35.2 +/- 18.3 mcmol/L; p<0.05) Improving the oxidative processes in peripheral tissues, L-carnitine increases the peripheral effectiveness of insulin and relieves the overstretched beta-cell apparatus.

Topics: Adult; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Carnitine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Islets of Langerhans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors; Tolbutamide

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Gluconeogenesis; Glucose Clamp Technique; Human Growth Hormone; Humans; Infusions, Parenteral; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Function Tests; Liver; Male; Middle Aged; Octreotide

A randomized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous (PV) and systemic venous (SV) drainage. Fourteen patients (SV) group) received systemically drained and sixteen (PV group) portally drained pancreas allografts. Enteric drainage was performed in both groups. The routine follow-up included documentation of the clinical course and detailed endocrine studies. At 1 year after transplantation, the patient survival rate was 92% for the SV group and 96% for the PV group; the graft survival rate was 78% and 82%, respectively. Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups. In addition, no hyperinsulinemia and lipidic abnormalities were evidenced in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences.

Topics: Adult; Anastomosis, Surgical; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drainage; Female; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Portal Vein; Triglycerides; Veins

A homogeneous patient population is necessary to identify genetic factors that regulate complex disease pathogenesis. In this study, we evaluated clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage renal disease (ESRD) probands of families in which nephropathy is clustered. C-peptide concentrations accurately discriminate type 1 from type 2 diabetic patients with normal renal function, but have not been extensively evaluated in ESRD patients. We hypothesized that C-peptide concentrations may not accurately reflect insulin synthesis in ESRD subjects, since the kidney is the major site of C-peptide catabolism and would poorly correlate with accepted clinical criteria used to classify diabetics as types 1 and 2.. Consenting diabetic ESRD patients (N = 341) from northeastern Ohio were enrolled. Clinical history was obtained by questionnaire, and predialysis blood samples were collected for C-peptide levels from subjects with at least one living diabetic sibling (N = 127, 48% males, 59% African Americans).. Using clinical criteria, 79% of the study population were categorized as type 1 (10%) or type 2 diabetics (69%), while 21% of diabetic ESRD patients could not be classified. In contrast, 98% of the patients were classified as type 2 diabetics when stratified by C-peptide concentrations using criteria derived from the Diabetes Control and Complications Trial Research Group (DCCT) and UREMIDIAB studies. Categorization was concordant in only 70% of ESRD probands when C-peptide concentration and clinical classification algorithms were compared. Using clinical phenotyping criteria as the standard for comparison, C-peptide concentrations classified diabetic ESRD patients with 100% sensitivity, but only 5% specificity. The mean C-peptide concentrations were similar in diabetic ESRD patients (3.2 +/- 1.9 nmol/L) and nondiabetic ESRD subjects (3.5 +/- 1.7 nmol/L, N = 30, P = NS), but were 2.5-fold higher compared with diabetic siblings (1.3 +/- 0.7 nmol/L, N = 30, P < 0.05) with normal renal function and were indistinguishable between type 1 and type 2 diabetics. Although 10% of the diabetic ESRD study population was classified as type 1 diabetics using clinical criteria, only 1.5% of these patients had C-peptide levels less than 0.20 nmol/L, the standard cut-off used to discriminate type 1 from type 2 diabetes in patients with normal renal function. However, the criteria of C-peptide concentrations> 0.50 nmol/L and diabetes onset in patients who are more than 38 years old identify type 2 diabetes with a 97% positive predictive value in our ESRD population.. Accepted clinical criteria, used to discriminate type 1 and type 2 diabetes, failed to classify a significant proportion of diabetic ESRD patients. In contrast to previous reports, C-peptide levels were elevated in the majority of type 1 ESRD diabetic patients and did not improve the power of clinical parameters to separate them from type 2 diabetic or nondiabetic ESRD subjects. Accurate classification of diabetic ESRD patients for genetic epidemiological studies requires both clinical and biochemical criteria, which may differ from norms used in diabetic populations with normal renal function.

Topics: Adult; Age of Onset; Algorithms; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Genetic Predisposition to Disease; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Male; Middle Aged; Phenotype; Predictive Value of Tests; Sensitivity and Specificity

The acute metabolic effects of recombinant human insulin-like growth factor-1 (rhIGF-1) were studied after an overnight fast in six maintenance hemodialysis (MHD) patients, six chronic peritoneal dialysis (PD) patients and six normal subjects. Each subject received a subcutaneous injection of rhIGF-1, 50 or 100 micrograms/kg body wt, given in random order on two occasions separated by 7 to 21 days. After the rhIGF-1 injection, plasma insulin, C-peptide, cortisol, amino acids and glucose decreased. The magnitude of the decrease was greater with the larger rhIGF-1 dose. The fall in plasma insulin, C-peptide and many amino acid concentrations was less and the decrease in glucose was similar in the MHD and CAPD patients as compared to normals. With 50 micrograms rhIGF-1/kg, plasma insulin and C-peptide decreased more quickly and often to a greater magnitude in normal individuals. With 100 micrograms rhIGF-1/kg, the decrease in plasma insulin, C-peptide and amino acids in the MHD and CAPD patients was almost as frequent as in the normal subjects, but the magnitude of the fall was often significantly less. This impaired response occurred in both MHD and CAPD patients even though, with the 100 micrograms rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than in normals during most of the first four hours after injection. These results provide the first in vivo evidence for resistance to the metabolic effects of rhIGF-1 in patients with advanced renal failure.

Topics: Adult; Amino Acids; Blood Glucose; C-Peptide; Case-Control Studies; Female; Glucagon; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis

Topics: Antilymphocyte Serum; Azathioprine; C-Peptide; Cells, Cultured; Cyclosporine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Immunosuppression Therapy; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Muromonab-CD3; Postoperative Complications; Prednisone; Tissue Preservation; Transplantation, Heterotopic; Transplantation, Homologous

We report the long-term metabolic observations made on 37 patients after simultaneous pancreas and kidney transplantation. Plasma C-peptide levels were above the physiological range in all patients and there was no significant difference between patients undergoing delayed duct occlusion (n = 12) or those with drainage of exocrine secretion into the urinary bladder (n = 25). HbA1c was equally at the upper end of the normal range in both subsets of patients. Mean fasting cholesterol (237 mg/dl) and triglycerides (122 mg/dl) were normal, and HDL-cholesterol was above normal with an average concentration of 77 mg/dl. Two patients underwent an oral fat tolerance test and showed extremely low postprandial lipaemia and very high lipoprotein lipase activities. We conclude that patients with a functioning pancreas graft persistently demonstrate normoglycaemia, elevated C-peptide, and a very favourable lipid profile both in the fasting and the postprandial state.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Lipids; Pancreas Transplantation

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

A 63-year-old man was diagnosed with diabetes mellitus at 42 years of age. He subsequently exhibited poor blood glucose control for a prolonged period, and his renal failure worsened. He therefore underwent hemodialysis and abdominal magnetic resonance imaging, which revealed a mass in the pancreatic tail. The immunoreactive insulin and C-peptide immunoreactivity levels were significantly elevated, and the results of a fasting test led to a diagnosis of insulinoma. The patient received treatment with oral diazoxide and continuous glucose monitoring (CGM), which resulted in the resolution of the hypoglycemia. This is a rare case of renal failure in which the CGM findings showed improvements in the blood glucose level after diazoxide administration.

Topics: Antihypertensive Agents; Biomarkers, Tumor; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diazoxide; Humans; Hypoglycemia; Insulin; Insulinoma; Kidney Failure, Chronic; Male; Middle Aged; Pancreatic Neoplasms; Renal Dialysis; Treatment Outcome; Vasodilator Agents

This study was designed to evaluate the impact of fructose-rich diet and chronic kidney disease (CKD) on the in vitro function of pancreatic islets.. Fifty-four rats were divided into 3 equal groups as follows: control, rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6 that underwent uninephrectomy and kidney cortex mass resection. Each group was further assigned to 3 diet protocols--regular diet, regular diet with 10% fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin administration, C-peptide, glycated hemoglobin level, serum urea nitrogen, creatinine clearance, and homeostasis model assessment of insulin resistance were evaluated. Static glucose insulin stimulation test of isolated pancreatic islets and histologic analysis of pancreatic tissue were performed.. The F10 diet increased the levels of insulin and C-peptide in all groups. Homeostasis model assessment of insulin resistance was increased in all animals fed with fructose. The elevated levels of creatinine and diminished creatinine clearance were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet resulted in high levels of serum insulin and C-peptide and glucose-stimulated insulin secretion. Fructose-rich diet increased the islet size and number, with irregular morphology and exocrine tissue fibrosis.. The fructose-rich diet accelerates the progression of CKD and affects the pancreatic islet function.

Topics: Animals; Body Weight; C-Peptide; Creatinine; Dietary Carbohydrates; Fructose; Glucose; Hypoglycemic Agents; In Vitro Techniques; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Kidney Failure, Chronic; Male; Rats, Wistar

Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic therapies. The aim of the present study was to identify differences between patients on oral antidiabetic drug therapy or insulin substitution or diet therapy alone during their first year of hemodialysis.. Sixty-four type 2 diabetic patients who had started hemodialysis (HD) at our dialysis center between 2003 and 2007 were included in the study. Kidney-transplanted patients (n = 1) and those with chronic infectious or malignant diseases (n = 4) were excluded. Patients were divided into three groups according to their antidiabetic therapy: group 1 consisted of patients on oral antidiabetic drug therapy (n = 12), group 2 of those on insulin therapy (n = 42), and group 3 of those being treated with diet alone (n = 10). At the start of HD and 12 months later, we measured fasting plasma glucose (FPG), HbA1c, the incidence of hypoglycemia (n/patient/month), cholesterol, triglycerides, body weight, and insulin requirements in the insulin-treated group. C-peptide was only measured at the start of dialysis. We evaluated changes in antidiabetic therapy during the first year on dialysis, and the prevalence of vascular disease in each group at the start of HD.. FPG and HbA1c values were similar in all groups at the start of HD and after 1 year. Hypoglycemia occurred more frequently in insulin-treated patients; however, the difference was not significant. Cholesterol levels were similar in all groups, whereas triglycerides were significantly lower in insulin-treated patients (138 ± 28 vs. 176 ± 46 mg/dl; P < 0.05). Body weight was similar in all groups. No significant change in body weight was observed in any group after 12 months on dialysis. At the start of HD, C-peptide levels were lower in insulin-treated patients than in the other groups (1.8 ± 0.9 ng/ml vs. 2.2 ± 1.1 and 2.4 ± 1.1 ng/ml; P < 0.05). During the first 12 months on HD, two patients from group 1 were shifted to group 3 (diet alone), while four patients could reduce their drug dosage (33%). However, two subjects became insulin-dependent. In group 2, insulin therapy could be terminated in two cases, while the insulin dose could be reduced in 20 patients (48%). In group 3, one patient was switched to oral antidiabetic therapy. The prevalence of vascular disease was slightly higher in group 3 (NS).. Within 1 year after the start of HD, the dose of sulfonylurea as well as insulin could be reduced in a large majority of patients. Metabolic control was similar in all groups. Only triglycerides were significantly lower in group 2. The frequency of hypoglycemia and the prevalence of vascular disease were just slightly higher in the group on insulin therapy.

Topics: Aged; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sulfonylurea Compounds; Triglycerides; Vascular Diseases

Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease.. To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m(2) and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT.. Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM.. SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.

Topics: Adult; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Follow-Up Studies; Glycated Hemoglobin; Graft Rejection; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Retrospective Studies; Survival Analysis; Tissue Donors

There is controversy regarding the place of simultaneous pancreas-kidney (SPK) transplantation in end-stage renal disease (ESRD) patients with insulin-dependent diabetes mellitus (IDDM) and detectable c-peptide. We sought to compare outcomes of recipients with and without pretransplantation c-peptide.. This retrospective single-center review included consecutive primary SPK transplantations performed between September 2007 and May 2010. Demographic characteristics and outcomes were compared between recipients with and without pretransplantation c-peptide.. Seven of 25 (28%) consecutive SPK transplant recipients with a diagnosis of IDDM and ESRD had detectable c-peptide prior to transplantation. The mean c-peptide level was 6.3 ± 6.1 ng/mL. For those recipients with and without c-peptide, mean age at diagnosis of IDDM (12.4 ± 7.8 vs 17.1 ± 6.6 years; P = not significant [NS]), duration of IDDM prior to transplantation (30 ± 10 vs 23 ± 9 years; P = NS), and body mass index (25.9 ± 4.5 vs 26.7 ± 4.5 kg/m(2); P = NS) were equivalent between the groups. With a median follow-up of 17 months (range, 3-35 months) there was 1 graft loss (due to cardiovascular death) among the 25 patients. At the most recent follow-up, for recipients with and without c-peptide, both the mean serum creatinine (1.3 ± 0.6 vs 1.0 ± 0.2 ng/mL; P = NS) and the mean HbA1c level (5.3 ± 0.4 vs 5.3 ± 0.5; P = NS) were equivalent between the groups.. For nonobese ESRD patients diagnosed with IDDM at a young age, the presence of detectable c-peptide should not influence the decision to proceed with SPK transplantation.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Retrospective Studies

The recurrence or persistence of pancreatic autoantibodies after pancreas-kidney transplantation (PKT) is an intriguing finding. We prospectively analyzed 77 PKTs, searching for risk factors for the expression of these autoimmune markers and their impact on pancreas graft function. Among the 77 PKTs, 24.7% had 0 HLA matches, 20.8% displayed delayed graft function, and 14.3% had acute rejection episodes. Immunosuppression included antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and steroids. Sixty-five patients had both grafts functioning as a follow-up of more than 6 months. In 11 patients anti-glutamic acid decarboxylase (GAD) positivity persists (n = 8) or has recurred (n = 3), 4 of whom show increasing titers. Two patients maintain positive islet cell antibodies (ICA) and anti-GAD antibodies. The 9 patients positive for ICA included 2 who were negative before PKT and 7 who remain positive. The "positive" group (22 patients with positive ICA and/or anti-GAD) did not differ from the global group of 65 functioning PKT in terms of acute rejection episodes, HLA match, and steroid withdrawal. Among the positive patients, there were 2 with borderline glucose levels; however, among the entire "positive" group, the mean fasting glucose, HbA1c, and C-peptide measurements were not significantly different, when compared with the other 65 PKTs. In conclusion, pancreatic autoantibodies may be persistently positive or recur after PKT, despite appropriate immunosuppression. Its impact on long-term pancreas graft survival is unknown. We could not identify risk factors for their expression. An extended follow-up with monitoring and search for other risk factors may be necessary to increase our knowledge in this field.

Topics: Adult; Autoantibodies; Blood Glucose; C-Peptide; Cadaver; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas; Pancreas Transplantation; Reference Values; Retrospective Studies; Tissue Donors; Young Adult

Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF) 1beta cause various phenotypes including maturity-onset diabetes of the young type 5 (MODY5) and kidney disease. We provide molecular and pathophysiologic characterization of a 23-year-old male patient with clinical presentation typical for MODY5 with renal involvement. Clinical studies (including intravenous glucose tolerance test and magnetic resonance imaging) of the patient and 5 family members in comparison with unrelated control subjects and molecular analysis of the HNF-1beta gene (direct sequencing, paternity testing, and restriction fragment length polymorphism analysis for parental mosaicism) were performed. The patient was born with low birth weight (2250 g), whereas his dizygotic twin sister was of normal weight (3500 g) and healthy. He had cystic renal dysplasia with progressive renal failure and pancreas atrophy with beta-cell dysfunction and early-onset diabetes mellitus but no family history of diabetes. Intravenous glucose tolerance test showed a markedly reduced but not absent acute insulin response compared with controls (n = 6). A mutation in the HNF-1beta gene S148L (C443T) in exon 2 within the pseudo-POU domain was identified. All other family members and the control group (n = 255) did not have the mutation, suggesting that we described a de novo mutation in HNF-1beta. Paternity was confirmed, and no signs of mosaicism in DNA analysis of both parents could be detected. Of note, the low birth weight of the patient in contrast to his healthy twin sister provides interesting support for the fetal insulin hypothesis for reduced birth weight.

Topics: Adult; Birth Weight; C-Peptide; Diabetes Mellitus, Type 2; DNA; Exons; Glucose Tolerance Test; Hepatocyte Nuclear Factor 1-beta; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Kidney; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Mutation; Paternity; Pedigree; Phenotype; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction

To investigate the contribution of HCV infection to insulin resistance in chronic haemodialysis patients.. The study was performed with 55 patients who were on regular haemodialysis therapy three times per week. Of the 55 patients, 34 (20 females and 14 males with an average age of 40.9 years) were anti-HCV (+) and were defined as the HCV (+) group. The remaining 21 patients (8 females and 11 males with an average age of 50 years) were negative for HCV and other viral markers and were defined as the HCV (-) group. BMI of all patients were below 27. Insulin resistance (IR) was calculated according to the HOMA formula and patients were called HOMA-IR (+) if their HOMA scores were higher than 2.5. All of the HOMA-IR (+) patients in both groups were called the HOMA-IR (+) subgroup. None of the patients had a history of drug use or any diseases that were related to insulin resistance except uremia. In both groups and the healthy control group, insulin and glucose levels were studied at three different venous serum samples taken at 5- minute intervals after 12 hours of fasting. Other individual variables were studied at venous serum samples taken after 12 hours of fasting.. HOMA scores were (3)2.5 in 22 of 34 HCV (+) patients (64.7%) and 7 of 21HCV (-) patients (33.33%) (p=0.024). Insulin levels of HCV (+) group (13.32 +/- 9.44mIU/mL) were significantly higher than HCV (-) (9.07 +/- 7.39mIU/mL) and the control groups (6.40 +/- 4.94mIU/ mL) (p=0.039 and p=0.021 respectively). HCV (+) patients were younger (40.94 +/- 17.06 and 52.62 +/- 20.64 years, respectively) and had longer dialysis duration (7.18 +/- 3.61 and 2.91 +/- 2.69 years, respectively). Significant positive correlations of HOMA score with insulin (r=0.934, p=0.000) and fasting glucose levels (r=0.379, p=0.043) were found in the HOMA- IR (+) subgroup. Also, a significant positive correlation was found between ALT and insulin levels in the HOMA IR (+) subgroup. C-peptide levels of both HCV (+) and (-) groups were significantly higher than the control group (p < 0.001). There were not any significant correlations between HOMA score and some of the other individual variables including levels of triglyceride, ferritin, ALT, iPTH and Mg in any of the groups.. In chronic haemodialysis patients; HCV infection is related to a high prevalence of insulin resistance, higher insulin and glucose levels.

Topics: Adult; C-Peptide; Female; Hepatitis C; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The purpose of this study was to evaluate whether islet transplantation may stabilize polyneuropathy in uremic type 1 diabetic patients (end-stage renal disease [ESRD] and type 1 diabetes), who received a successful islet-after-kidney transplantation (KI-s).. Eighteen KI-s patients underwent electroneurographic tests of sural, peroneal, ulnar, and median nerves: the nerve conduction velocity (NCV) index and amplitudes of both sensory action potentials (SAPs) and compound motor action potentials (CMAPs) were analyzed longitudinally at 2, 4, and 6 years after islet transplantation. Skin content of advanced glycation end products (AGEs) and expression of their specific receptors (RAGE) were also studied at the 4-year follow-up. Nine patients with ESRD and type 1 diabetes who received kidney transplantation alone (KD) served as control subjects.. The NCV score improved in the KI-s group up to the 4-year time point (P = 0.01 versus baseline) and stabilized 2 years later, whereas the same parameter did not change significantly in the KD group throughout the follow-up period or when a cross-sectional analysis between groups was performed. Either SAP or CMAP amplitudes recovered in the KI-s group, whereas they continued worsening in KD control subjects. AGE and RAGE levels in perineurium and vasa nervorum of skin biopsies were lower in the KI-s than in the KD group (P < 0.01 for RAGE).. Islet transplantation seems to prevent long-term worsening of polyneuropathy in patients with ESRD and type 1 diabetes who receive islets after kidney transplantation. No statistical differences between the two groups were evident on cross-sectional analysis. A reduction in AGE/RAGE expression in the peripheral nervous system was shown in patients receiving islet transplantation.

Topics: Adult; Biomarkers; Biopsy; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Electrophysiology; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Longitudinal Studies; Middle Aged; Peripheral Nerves; Skin

Herein we report 10- to 15-year results of simultaneous pancreas-kidney (SPK) transplants in 135 type I and type II insulin-dependent diabetes mellitus (IDDM) patients.. Diabetes type was defined by the absence (type I) or presence (type II) of C-peptide. The freedom from dialysis and need for insulin defined graft survival. Patient survival was verified by record review and the Social Security Death Registry. The mean follow-up exceeded 100 months.. Type II IDDM present in 28% of the 135 cohort, predominately among African-Americans (AA). The type II group was two-thirds AA (43% of the total AA patients) and 17% of the non-African-American (nAA) group. The difference between the two groups by C-peptide level was significant (P = .001). Type II patients had a higher body mass index, were slightly older at the onset of DM, but had similar duration of IDDM before ESRD. At 5 and 10 years, pancreas survival for type 1 DM was 71% and 49%; for type II DM it was 67% and 56% (P = .52). Kidney survival for type I DM was 77% and 50%; for type II it was 72% and 56% (P = .65). Patient survival for type I DM was 85% and 63%; for type II DM it was 73% and 70% (P = .98).. We conclude that the outcomes of SPK transplants are equivalent regardless of diabetes type. Accordingly, the decision whether to perform pancreas transplants in diabetic recipients of kidney allografts should be based on general acceptance criteria not diabetes type.

Topics: Adult; Black People; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; District of Columbia; Follow-Up Studies; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pancreas Transplantation; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome

Diabetic patients with end-stage renal disease have a high mortality rate. A combined kidney-pancreas transplant is associated with greater life expectancy. Pancreas islet transplantation is an alternative involving a lower degree of morbidity. We present two patients, of 41 and 37 years of age, with a long history of diabetes mellitus (C-peptide negative), both with a previous kidney transplant, who had been treated with 22 and 28 U of insulin/d, respectively. Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one patient required occasional doses of insulin, and the other patient more than 50% reduced dose. After the first implant neither patient had any episodes of unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no transplant-related complications.

Topics: Adult; Awareness; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Complications; Postoperative Period

For selected patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous kidney-pancreas (SKP) or pancreas after kidney (PAK) transplantation is the treatment of choice. However, it is frequently difficult to start a program for fear of serious intraabdominal complications in an immunosuppressed patient. We review our initial experience with these transplantations.. Twenty-three patients (20 SKP, 3 PAK) with type 1 diabetes mellitus received transplants between June 2000 and October 2003. All received immunosuppression therapy with thymoglobulin, prednisone, tacrolimus, and mycophenolate mofetil. The operation included portal venous drainage and exocrine enteric drainage. Rejections were biopsy-proved. Cytomegalovirus prophylaxis with gancyclovir was administered.. The mean follow-up is 13 months (range, 1-30 months) for recipients of mean age 39 +/- 7 years (17 men, 6 women). Mean cold ischemia time for kidney was 10.2 +/- 3.9 hours, and for pancreas was 10.5 +/- 3 hours. The rate of initial graft function was 100%. Graft rejection rate was 8%. The repeat laparotomy rate was 53% (12 patients), with a mean of 0.8 procedures per patient (range, 0 to 5). At the end of follow-up, patient survival was 95%, kidney survival was 85%, and pancreas survival was 83%. Patients with a functioning graft were insulin-free, with a mean fasting glucose concentration of 79 +/- 7 mg/dL, hemoglobin A1C of 4.5% (range, 4% to 4.9%) C-peptide of 5.9 ng/mL (range, 2.1 to 12 ng/mL), and a mean serum creatinine level of 1.6 mg/dL (range, 0.9 to 4.6 mg/dL). There was 1 death, due to posttransplantation lymphoproliferative disease confined to the pancreatic graft and abdominal sepsis at 3 months posttransplantation.. Our results are similar to those of other series of SPK or PAK transplantations: low acute rejection rates, frequent requirement for repeat laparotomy, and good patient and graft survival, permitting an excellent quality of life.

Topics: Adult; C-Peptide; Cytomegalovirus Infections; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Hematoma; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Reoperation; Time Factors

Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant.. The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 +/- 0.3 years from kidney transplant).. The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P < 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 +/- 0.08 to 2.78 +/- 0.44 mg/dl, P < 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 +/- 0.01 to 0.68 +/- 0.01%, P < 0.01; KI-s at baseline: 0.72 +/- 0.02 to 0.69 +/- 0.02%, P < 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 +/- 9.0 to 82.9 +/- 33.6 mg/l, P < 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown).. In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function.

Topics: Adult; Biopsy; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Glycated Hemoglobin; Graft Survival; Humans; Hypertrophy; Immunosuppression Therapy; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Survival Analysis; Time Factors; Treatment Outcome

Even recipients with satisfactory function of transplanted pancreas and kidney may show physical and/or social disability due to diabetic complications. Our aims were to evaluate diabetic complications influencing recipient quality of life and to assess patients' psychosociological status. Nineteen patients with functioning grafts who consented to take part in the study, underwent clinical evaluation and answered questions regarding their quality of life. Results showed excellent endocrine pancreatic function in 17 patients. In most recipients, insulin activity and C-peptide levels were elevated owing to systemic venous drainage. Opthalmological examination revealed blindness in 7 patients (in 4 cases with onset following SPKTx) and retinopathy in 13 patients (in 5 cases it appeared after SPKTx). Assessment of the cardiovascular system revealed satisfactory cardiac function in 16 of 19 patients; 4 patients underwent amputation of a lower limb following SPKTx. All 19 recipients admitted to a great benefit of transplantation; most patients declared ability to organize their life activity and social functions and 4 had regular employment. Conversely, most patients were afraid of graft loss, and half were often sad and even depressed.

Topics: Blindness; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Employment; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Pancreas Transplantation; Postoperative Complications; Quality of Life

The aim of this study was to assess the selection of candidates among 38 dialyzed diabetic patients referred between January 1, 1998 and December 31 2002 for kidney followed by islet transplantation (IAK). The main criteria of eligibility for possible IAK were as follows: (1) plasma C-peptide negative; (2) need for a kidney graft; (3) kidney plus whole pancreas transplantation not desired by the patient; and (4) acceptable results of postkidney graft preislet transplantation evaluation.. Seventeen of 38 patients with positive C-p diabetes received a kidney graft alone. Among the 21 C-p-negative diabetic patients, 3 were not eligible for kidney transplantation mainly for psychological reasons and 4 were eligible for kidney plus pancreas transplantation. The remaining 14 C-p-negative patients underwent kidney transplantation or had previously undergone kidney transplantation. Among them, 1 had moved away, 1 refused IAK, one had slightly positive stimulation tests, 1 was overweight, 1 had breast cancer, and 1 had postkidney graft complications. Among the remaining 8 of 14 C-p-negative, kidney-engrafted patients listed for IAK, 5 have undergone transplantation, 3 with a pre-Edmonton and 2 with the Edmonton protocol.. In conclusion among this series of 38 diabetic patients undergoing dialysis, more than 90% were kidney-grafted. Approximately 50% were ineligible for pancreas transplantation or IAK because of a positive C-p, and 20% were enlisted for IAK. These results highlight the importance of C-p determinations in diabetic dialysis patients to identify eligible patients for pancreas transplantation or IAK.

Topics: Adult; Aged; Biomarkers; C-Peptide; Diabetic Nephropathies; Eligibility Determination; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Patient Selection; Renal Dialysis

Since the Edmonton protocol, islet transplantation (IT) offers the prospect of adequate glycemic control with no major surgical risk. In our single-center experience of IT, we studied the recruitment of eligible diabetic patients.. Between 1998 and 2002, we screened 79 diabetic patients that were divided into 2 groups according to their renal status: 41 were not receiving dialysis (ND) while 38 were receiving ongoing dialysis (D).. In the ND group, 20 patients initiated the contact with our team, 8 patients were recruited during hospitalization for very poor glycemic imbalance, and 13 were referred by their diabetologist. 14/41 (34%) patients were ineligible for IT either because of very good glycemic balance, detectable C-peptide (C-p), kidney or liver problems, or plans for future pregnancy. 16/41 (39%) did not wish to proceed, 7 of whom were more interested by a pump. 11/41 (27%) were eligible, among which 8 are currently being assessed, 1 is on the waiting list and 2 have been transplanted. In the D group, 17/38 (45%) had a detectable C-p and received a kidney graft alone. Among the remaining 21 C-p negative diabetic patients, 3 were not eligible for kidney transplantation mainly for psychological reasons, and 4 were enlisted for kidney+pancreas transplantation. The remaining 14 C-p negative patients were kidney-transplanted. Among them, 6 were not eligible for IT, mainly for lack of motivation, slightly positive C-p stimulation tests, obesity, cancer, or increased creatininemia. The remaining 8/14 C-p negative kidney-engrafted patients were enlisted for IT. 3 had secondary failure with the pre-Edmonton immunosuppressive (IS) protocol. Five have been transplanted with the Edmonton-like IS regimen.. Twenty-five per cent of the 79 patients for whom islet transplantation was considered underwent pregraft assessment and 12% (10 patients, 8 kidney-transplanted and 2 islet alone) of the 79 have been transplanted. The main eligibility criteria were undetectable Cpeptide, normal kidney function, average weight, glycemic imbalance, hypoglycemia unawareness, and glycemic brittleness.

Topics: Adult; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Male; Middle Aged; Patient Selection; Renal Replacement Therapy; Retrospective Studies; Treatment Outcome

Topics: Adult; Blood Glucose; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Dose-Response Relationship, Drug; Histocompatibility Testing; Humans; Insulin; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Reoperation; Treatment Outcome

A diabetic patient with chronic renal failure who developed recurrent and prolonged episodes of hypoglycemia associated with use of sulfonylurea agent is presented here. This patient was hospitalized with neuroglycopenic symptoms of hypoglycemia that persisted in spite of large doses of parenteral glucose replacement. On administration of somatostatin analogue octreotide, hypoglycemia resolved and, blood glucose levels were maintained even after cessation of parenteral glucose. The patient received 2 subcutaneous doses of octreotide 12 hours apart, and made a complete recovery. Our experience suggests that use of octerotide to treat refractory or prolonged sulfonylurea-included hypoglycemia in renal failure patients is safe and effective; large prospective studies would be needed to validate these findings.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Gastrointestinal Agents; Glipizide; Humans; Hypoglycemia; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Octreotide; Seizures

Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients.. A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and D-dimer fragment (DDF)] were studied cross-sectionally.. The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, chi(2) = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: delta1-3 years -13 +/- 30 micro m vs. UI-K group: delta1-3 years 245 +/- 20 micro m, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 +/- 4.5% vs. UI-K 0.5 +/- 2.7%, P = 0.02), higher basal NO (SI-K 42.9 +/- 6.5 vs. UI-K 20.2 +/- 6.8 micro mol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 +/- 15.3 vs. UI-K 180.6 +/- 7.0%, P = 0.02) and DDF (SI-K 0.61 +/- 0.22 vs. UI-K 3.07 +/- 0.68 micro g/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF.. Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patients.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Survival Rate; Time Factors; Treatment Failure; Treatment Outcome

An end-stage renal disease patient on long-term peritoneal dialysis was admitted with dizziness, fatigue, hypoglycemia, and hypotension. The hypotension resolved with intravenous normal saline, but the hypoglycemia persisted for 3 days despite an intravenous dextrose drip and discontinuation of gabapentin. The patient became normoglycemic on the fourth day of admission. None of the known causes for the hypoglycemia were identified except gabapentin, the dose of which was recently doubled 1 month before admission. Insulin and C-peptide levels were high during the hypoglycemic episode and returned to normal after discontinuation of gabapentin. The patient remains off gabapentin and has had no further episodes of hypoglycemia. To our knowledge, this is the first case of hypoglycemia induced by gabapentin.

Topics: Acetates; Amines; C-Peptide; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Gluconeogenesis; Humans; Hypoglycemia; Hypotension; Insulin; Kidney Cortex; Kidney Failure, Chronic; Liver; Middle Aged; Pancreas; Parathyroidectomy; Peritoneal Dialysis; Postoperative Complications

Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. In the present study, we investigated the stage of renal failure in which abnormalities of glucose metabolism develop and whether these abnormalities were associated with an increased prevalence of cardiovascular events in patients with early renal failure. In 321 untreated essential hypertensive patients, we assessed renal function by measuring 24-h creatinine clearance, urinary protein excretion, and microalbuminuria; we assessed cardiovascular status by clinical and laboratory tests; and we measured plasma glucose, insulin, and C-peptide levels at fasting and after a 75-g oral glucose load. To evaluate insulin sensitivity, a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 104 patients. Patients with creatinine clearance < 30 ml.min(-1).1.73 m(-2), severe hypertension, BMI < 30 kg/m(2), and diabetes or family history of diabetes were excluded. Hypertensive patients were found to be hyperinsulinemic when compared with 92 matched normotensive subjects. Early renal failure (creatinine clearance < 90 ml.min(-1).1.73 m(-2)) caused by hypertensive nephrosclerosis was detected in 116 of 321 patients. Analysis of patients with varying degrees of renal function impairment demonstrated increased plasma glucose and insulin response to oral glucose load, decreased fasting glucose-to-insulin ratio, and reduced sensitivity to insulin only in those patients with creatinine clearance < 50 ml.min(-1).1.73 m(-2). Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without evidence of atherosclerotic damage. Thus, in patients with hypertensive nephrosclerosis and early impairment of glomerular filtration, alterations of glucose metabolism become evident only when creatinine clearance is < 50 ml.min(-1).1.73 m(-2) and are not related to microalbuminuria and cardiovascular complications.

Topics: Albuminuria; Blood Glucose; Body Mass Index; C-Peptide; Creatinine; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypertension; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Reference Values; Smoking; Triglycerides

Topics: Aged; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Histocompatibility Testing; Humans; Insulin; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Reoperation; Treatment Outcome

Topics: Antibodies, Monoclonal; Basiliximab; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Glycated Hemoglobin; Graft Survival; Humans; Immunosuppressive Agents; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Recombinant Fusion Proteins; Reoperation; Retrospective Studies; Time Factors; Transplantation, Homologous

We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years.. Of the 49 African-Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P>0.05). The actuarial 10-year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups.. The data strongly suggest that pretransplant C-peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race.

Topics: Black People; C-Peptide; Diabetes Mellitus, Type 1; Follow-Up Studies; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pancreas Transplantation; Time Factors

Abnormalities of the growth hormone (GH)/ insulin-like growth factor (IGF) axis have been reported in children with chronic renal failure (CRF) and post-transplant, and are thought to contribute to poor growth. This study examined the effect of CRF and steroid therapy (given post-transplant and to children with normal renal function) on the GH-IGF axis in children with normal and abnormal growth. Thirty-one children with CRF, ten on dialysis, 26 with renal transplants and ten taking steroid therapy but with normal renal function, were studied. IGF-I, measured by radioimmunoassay, was normal but IGF bioactivity was low in groups with a decreased glomerular filtration rate (P<0.05). Transplanted children growing at a subnormal growth rate had lower IGF bioactivity than those growing at a normal rate (P=0.03), but there was no such difference in bioactivity in children with CRF. There was no correlation between IGF bioactivity and prednisolone treatment. There was no correlation between IGF binding proteins 1, 2 or 3 and growth.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Female; Glomerular Filtration Rate; Glucocorticoids; Growth; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Kidney Failure, Chronic; Kidney Transplantation; Male; Prednisolone; Renal Dialysis; Somatomedins

Our aim was to compare the diurnal blood pressure patterns of people with Type 1 diabetes on continuous ambulatory peritoneal dialysis (CAPD, n=9) or haemodialysis (n=10) to diabetic patients with normo-albuminuria (n=12) or micro-albuminuria (n=15). Blood pressure was measured with an ABPM02 Meditech oscillometric blood pressure monitor. The micro-albuminuric group had significantly higher nocturnal diastolic and mean arterial pressures than the normo-albuminuric group. CAPD and haemodialysis patients had significantly higher day time, nocturnal mean systolic, diastolic and mean arterial blood pressures. Micro-albuminuric and end-stage renal failure patients displayed a loss of the physiological drop of systolic blood pressure, which was only significant in the normo-albuminuric group. Nocturnal drop of blood pressure characterised by diurnal indices were 7.4% in the CAPD, 8.8% in the haemodialysis, 10.0% in the micro-albuminuric and 16.5% in the normo-albuminuric group. These results suggest, that pathological circadian blood pressure variation is common in diabetic patients on dialysis, and ambulatory blood pressure monitoring can be a useful tool both in its the detection and its adequate treatment.

Topics: Adult; Albuminuria; beta 2-Microglobulin; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood Urea Nitrogen; C-Peptide; Cholesterol; Circadian Rhythm; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Triglycerides

Leptin is a protein hormone produced predominantly by adipocytes that affects food intake and energy expenditure. Its serum levels are significantly higher in patients with chronic renal failure compared to healthy subjects. The aim of this study was to compare serum leptin levels in hemodialyzed patients with type II diabetes mellitus (n=26) with body content-matched hemodialyzed patients without diabetes (n=26) and to explore the relationship between parameters of the long term diabetes metabolic control and serum leptin levels. Serum leptin levels in diabetic patients did not significantly differ from those of non-diabetic patients (25.3+/-8.8 vs 25.7+/-8.7 ng/ml). Serum leptin levels in diabetic patients positively correlated with body fat content, body mass index and predialysis serum insulin levels. No significant relationship were observed between serum leptin levels and blood glucose, glycated hemoglobin, glycated protein, serum urea, creatinine, leukocyte count and total hemoglobin respectively. The multiple stepwise regression analysis revealed that body fat content together with body mass index accounted for 77.8% of variations in predialysis serum leptin levels, while insulin levels and the parameters of diabetes metabolic control had only slight prediction value for leptin concentrations. We conclude that serum leptin levels in hemodialysed patients with type III diabetes mellitus do not significantly differ from those of hemodialysed non-diabetic patients. The body fat content and body mass index are the strongest predictors of serum leptin levels, while parameters of long term diabetes metabolic control play probably only minor direct role in its regulation.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Reference Values; Regression Analysis; Renal Dialysis; Urea

Topics: C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Taiwan; Time Factors

The aim of this study was to determine the glucose-dependent regulation of the sodium-proton-antiporter (Na+/H+ antiporter) in patients with mild chronic renal failure (CRF).. We measured plasma glucose concentrations, plasma insulin concentrations, plasma C peptide concentrations, arterial blood pressure, cytosolic pH (pHi), cellular Na+/H+ antiporter activity, and cytosolic sodium concentration ([Na+]i) in 19 patients with CRF and 41 age-matched healthy control subjects (control) during a standardized oral glucose tolerance test. Intracellular pHi, [Na+]i, and Na+/H+ antiporter activity was measured in lymphocytes using fluorescent dye techniques.. Under resting conditions, the pHi was significantly lower, whereas the Na+/H+ antiporter activity was significantly higher in CRF patients compared with controls (each P < 0.0001). The oral administration of 100 g glucose significantly increased the Na+/H+ antiporter activity in CRF patients from 13.35 +/- 1.26 x 10-3 pHi/second to 16.44 +/- 1.37 x 10-3 pHi/second after one hour and to 14.06 +/- 1.36 x 10-3 pHi/second after two hours (mean +/- SEM, P = 0.008 by Friedmans's two-way analysis of variance). In controls, the administration of 100 g glucose significantly increased the Na+/H+ antiporter activity from 4.23 +/- 0.20 x 10-3 pHi/second to 6.00 +/- 0.56 x 10-3 pHi/second after one hour and to 6.65 +/- 0.64 x 10-3 pHi/second after two hours (P = 0.0003). The glucose-induced enhancement of the Na+/H+ antiporter activity was more pronounced in CRF patients compared with controls (P = 0.011). Resting [Na+]i was not significantly different between the two groups.. CRF patients show an intracellular acidosis leading to an increased Na+/H+ antiporter activity. In addition, high glucose levels exaggerate the differences in Na+/H+ antiporter activity already present between cells from patients with mild CRF and those from control subjects.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Cells, Cultured; Cytosol; Female; Glucose; Glucose Tolerance Test; Heart Rate; Humans; Hydrogen-Ion Concentration; Insulin; Kidney Failure, Chronic; Lymphocytes; Male; Middle Aged; Reference Values; Sodium; Sodium-Hydrogen Exchangers

Although glycemic control has an important impact on the clinical outcomes of patients with diabetes undergoing dialysis, there is a paucity of data on the relationship between glucose metabolism and clinical parameters in these patients. In this study, we compared a cohort of 48 patients with type II diabetes undergoing continuous ambulatory peritoneal dialysis (CAPD) with 84 age- and sex-matched patients with type II diabetes with similar disease duration but normal renal function. Compared with those with normal renal function, patients with type 2 diabetes undergoing CAPD had greater serum angiotensin-converting enzyme activity (median, 57.4 U/L; range, 33.5 to 100.0 U/L v 46.9 U/L; range, 11.6 to 111.2 U/L; P < 0.005), fasting C-peptide (median, 9.1 ng/mL; range, 0.9 to 30.0 ng/mL v 2.2 ng/mL; range, 0.2 to 20.3 ng/mL; P < 0.0001) and triglyceride levels, and lower serum albumin concentrations. Among the patients undergoing CAPD, there was a preponderance of men in the insulin-treated group. Insulin-treated patients also had greater plasma albumin levels and body weights and lower fasting serum C-peptide levels (2.81 +/- 1.77 v 3.12 +/- 2.04 ng/mL; analysis of variance, P = 0.007 adjusted for fasting glucose concentration). Multivariate analysis showed duration of diabetes, hemoglobin A(1c) (HbA(1c)) level, and body weight were independent determinants of insulin requirement in patients undergoing CAPD. The daily insulin dosage required was related to the duration of diabetes (r = 0.5; P = 0.007). In summary, among patients with end-stage renal failure, insulin-treated patients had greater body weights and plasma albumin levels but lower cholesterol levels. Plasma C-peptide concentration and duration of diabetes were the main determinants of insulin requirement, reflecting a decrease in beta-cell reserve, whereas the daily insulin dose correlated mainly with body weight, HbA(1c) level, and duration of diabetes. Kt/V had no effect on insulin resistance or insulin requirement of the patients.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Peptidyl-Dipeptidase A; Peritoneal Dialysis, Continuous Ambulatory; Serum Albumin; Treatment Outcome

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Somatostatin; Uremia

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

To determine the relationship between plasma leptin and insulin-like growth factor-I (IGF-I) levels in healthy subjects and patients with chronic renal insufficiency at baseline, and during administration of recombinant human IGF-I in the renal impaired patients.. 20 healthy subjects (six men, 14 women, age: 42.7 +/- 3.2 y) and nine subjects with chronic renal insufficiency (five men, four women, age: 53.6 +/- 3.7 y).. Daily s.c. injection of recombinant human IGF-I (50 micrograms/kg) for 24 d.. Fasting plasma levels of leptin, IGF-I, growth hormone, C-peptide, glucagon and IGF binding proteins by specific radioimmunoassays at baseline in all subjects and serially during IGF-I therapy in the renal impaired subjects.. Baseline leptin levels were correlated with body mass index (BMI, R = 0.72, P = 0.0001) but not IGF-I levels (R = 0.02). During IGF-I therapy, plasma IGF-I levels increased from 128 +/- 17.4 ng/ml at baseline to 250 +/- 36.8 ng/ml on day 3 (P = 0.003) and 323 +/- 61.6 ng/ml on day 24 (P = 0.01), whereas leptin levels declined: 24.4 +/- 10.3 ng/ml (baseline), 19.5 +/- 6.2 ng/ml (day 3, P = 0.028), and 17.2 +/- 4.9 ng/ml (day 24, P = 0.05).. Basal plasma leptin and IGF-I levels are not correlated; however, chronic administration of recombinant IGF-I is associated with an early and sustained decrease in plasma leptin levels. IGF-I may have an inhibitory effect on leptin secretion in humans.

Topics: Adult; Binding Sites; Body Mass Index; C-Peptide; Female; Glucagon; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay; Receptor, IGF Type 1; Receptors, Leptin; Recombinant Proteins

Hypoglycaemia is an important complication of insulin treatment in Type 1 diabetes mellitus (DM). Pancreas transplantation couples glucose sensing and insulin secretion, attaining a distinctive advantage over insulin treatment. We tested whether successful transplantation can avoid hypoglycaemia in Type 1 DM. Combined kidney and pancreas transplanted Type 1 DM who complied with good function criteria (KP-Tx, n = 55), and isolated kidney or liver transplanted non-diabetic subjects on the same immunosuppressive regimen (CON-Tx, n = 14), underwent 1-day metabolic profiles in the first 3 years after transplantation, sampling plasma glucose (PG) and pancreatic hormones every 2 hours. KP-Tx had lower PG than CON-Tx in the night and in the morning and higher insulin concentrations throughout the day. KP-Tx had lower PG nadirs than CON-Tx (4.40+/-0.05 vs 4.96+/-0.16 mmol l(-1), ANOVA p = 0.001). Nine per cent of KP-Tx had hypoglycaemic values (PG < or = 3.0 mmol l(-1)) in the profiles, both postprandial and postabsorptive, whereas none of CON-Tx did (p < 0.02). In conclusion, after pancreas transplantation, mild hypoglycaemia is frequent, although its clinical impact is limited. Compared to insulin treatment in Type 1 DM, pancreas transplantation improves but cannot eliminate hypoglycaemia.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Humans; Hypoglycemia; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Pancreas Transplantation; Postoperative Complications; Time Factors

To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications.. The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups.. The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years.. Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Topics: Adult; Age Factors; Age of Onset; Arteriosclerosis; Blindness; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Japan; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies

Topics: C-Peptide; Cholecystectomy, Laparoscopic; Cholelithiasis; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged

Topics: Adult; Bone Marrow Transplantation; C-Peptide; Cadaver; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Time Factors; Tissue Donors; Transplantation Chimera

Topics: C-Peptide; Cell Separation; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Retrospective Studies; Time Factors; Transplantation, Homologous; Treatment Failure; Treatment Outcome

We have examined the effect of a four-week intravenous treatment with 1 alpha-hydroxyvitamin D3 on insulin sensitivity in 14 patients on chronic hemodialysis compared with 10 healthy control subjects by the insulin tolerance test. Compared to controls, the uremic patients have featured increased levels of parathyroid hormone (1085.0 +/- 822.1 vs 74.2 +/- 8.7 pg/ml, p < 0.001), insulin resistance (the rate constant for plasma glucose disappearance, K(in): 3.1 +/- 0.5 vs 4.5 +/- 0.4%/dk, p < 0.002), increased levels of insulin (30.5 +/- 7.3 vs 20.4 +/- 2.8 microIU/ml, p < 0.04) and increased levels of C-peptide (6.0 +/- 2.1 vs 3.9 +/- 12, ng/ml, p < 0.001). Following treatment with 1 alpha-hydroxyvitamin D3, levels of parathyroid hormone decreased from 1085.0 +/- 822.1 to 772.1 +/- 620.1 pg/ml (p < 0.004), the K(in) values increased significantly (from 3.1 +/- 0.5 to 4.1 +/- 0.4%/dk, p < 0.004) and reached the level near to that of controls, the insulin concentrations decreased from 30.5 +/- 7.3 to 28.7 +/- 9.2 microIU/ml (p > 0.05) and C-peptide concentrations increased from 6.0 +/- 2.1 to 7.5 +/- 2.5 ng/ml (p < 0.02). In summary, uremic patients with secondary hyperparathyroidism developed insulin resistance and hyperinsulinemia. Intravenous 1 alpha-hydroxyvitamin D3 treatment has improved insulin sensitivity directly or by reducing secondary hyperparathyroidism in uremic patients on chronic hemodialysis.

Topics: Adult; Blood Glucose; C-Peptide; Calcium; Female; Glucose Tolerance Test; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Infusions, Intravenous; Insulin Resistance; Kidney Failure, Chronic; Male; Parathyroid Hormone; Radioimmunoassay; Renal Dialysis; Treatment Outcome

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Florida; Follow-Up Studies; Glycated Hemoglobin; Hispanic or Latino; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Retrospective Studies

Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Follow-Up Studies; Glomerular Filtration Rate; Glucose; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Kidney Failure, Chronic; Kidney Transplantation; Liver; Liver Glycogen; Longitudinal Studies; Middle Aged; Multivariate Analysis; Pancreas Transplantation; Prospective Studies; Time Factors

Islet amyloid polypeptide (IAPP), or amylin, is synthesized by beta cells in the islets of Langerhans of the pancreas. Plasma IAPP levels are highly elevated in patients with advanced renal failure. To investigate the involvement of the kidney in the clearance of IAPP, the response of plasma and urinary IAPP to a carbohydrate-rich meal was investigated in 14 healthy volunteers. Although plasma IAPP levels increased severalfold after the meal, no IAPP-immunoreactivity was detected in the urine samples up to 4 hours after the meal. This might be due to the fact that urinary IAPP levels are under the detection limit of the assay or, assuming the presence of IAPP in the primary urine, immunoreactive IAPP molecules may be processed by renal mechanisms in such a way that they are no longer recognized by the antibodies used in the radioimmunoassay. Processed IAPP molecules may be reabsorbed in the proximal tubules of the kidney and/or excreted.

Topics: Adult; Amyloid; Blood Glucose; C-Peptide; Dietary Carbohydrates; Eating; Fasting; Humans; Islet Amyloid Polypeptide; Kidney Failure, Chronic; Radioimmunoassay; Reference Values; Time Factors

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Liver Failure; Liver Transplantation; Middle Aged; Pancreas Transplantation; Patient Selection; Retrospective Studies; Transplantation, Autologous; Transplantation, Homologous

The authors studied hormonal regulation of carbohydrate metabolism by secretion of insulin, C-peptide in 86 patients with chronic glomerulonephritis with different functional condition of the kidneys. There was a decrease in glucose tolerance, basal and reactive hyperinsulinemia, elevated level of C-peptide (relative insulin insufficiency). Mechanism of arising changes in the carbohydrate and insulin metabolism is complex and multicomponent. This includes renal lesion and consequent inhibition of hormone metabolism. Intensification of glomerular filtration is associated with inhibition of filtration of insulin and C-peptide derivants. Accumulation of nitrogen metabolism products results in changed response of pancreatic beta-cells to glucose. General disturbances of metabolism are accompanied by increasing levels of hormonal and nonhormonal contrainsular substances.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Carbohydrates; Chronic Disease; Female; Glomerulonephritis; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Kidney; Kidney Failure, Chronic; Male; Time Factors

Topics: Adult; Blood Glucose; C-Peptide; Cell Separation; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Graft Rejection; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Care; Transplantation, Homologous; Treatment Outcome

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Duodenum; Female; Follow-Up Studies; Glucose; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Male; Pancreas Transplantation; Time Factors

In order to examine the role of endogenous opioid peptides on glucose metabolism in uraemic patients, plasma concentrations of beta-endorphin, glucose, insulin and C-peptide were determined before and during an oral glucose tolerance test (OGTT) in nine non-dialysed patients with chronic renal failure (CRF). The results are compared with those obtained in a group of age-matched normal subjects. In CRF patients, plasma beta-endorphin fasting values (16.0 +/- 1.9 pmol/l) were significantly higher than those of the controls (6.6 +/- 0.6 pmol/l) and significantly correlated with the degree of renal function impairment. After glucose load, plasma beta-endorphin in CRF patients tended to decline, whereas in normal subjects increased. The fasting and the mean OGTT plasma beta-endorphin values negatively correlated with insulin initial response to glucose, insulin and C-peptide mean OGTT values, but not with glucose OGTT mean values. Data indicate that chronic uraemia induces a significant increase in circulating plasma beta-endorphin levels, with a loss of opioid system responsiveness to glucose. The possibility that this hyper-endorphinism may have a biological importance at least as a contributory factor of impaired glucose tolerance in uraemia may be suggested.

Topics: Adult; Aged; beta-Endorphin; Blood Glucose; C-Peptide; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Time Factors

Considering that PAI-1 is an important factor modulating the systemic fibrinolytic activity, the abnormal insulin metabolism frequently seen in end-stage renal disease (ESRD) may cause decreased fibrinolytic activity in concert with PAI-1. To study this possibility, we measured insulin levels and compared it with the fibrinolytic profiles in ESRD patients. Fasting blood sugar, insulin, and C peptide levels were higher in ESRD patients than in the control group. In the ESRD patients, the insulin levels showed a positive correlation with C peptide (r = 0.612, p = 0.0001), fasting blood sugar (r = 0.334, p = 0.044), and PAI-1 antigen (r = 0.474, p = 0.0001) and a reverse correlation with euglobulin fibrinolytic activity (r = 0.5, p = 0.005), but no correlation with t-PA antigen. The euglobulin fibrinolytic activity showed a reverse correlation with PAI-1 antigen (r = 0.289, p = 0.0144), but no correlation with t-PA antigen. Our results suggest that abnormal insulin metabolism and/or insulin resistance, which occur frequently in ESRD, may play an important role in the decrease in systemic fibrinolytic activity by the regulation of the PAI-1 concentration.

Topics: Blood Glucose; C-Peptide; Enzyme-Linked Immunosorbent Assay; Female; Fibrinolysin; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Renal Dialysis

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Parenteral Nutrition, Total; Prednisolone; Time Factors; Transplantation, Homologous

Topics: Adult; Azathioprine; Blood Glucose; C-Peptide; Creatinine; Cyclosporine; Diabetes Mellitus, Type 1; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pancreas Transplantation

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

Amylin, a 37 amino acid polypeptide, has been suggested to play a prominent role in the pathogenesis of insulin resistance in type II diabetes mellitus. Various studies have demonstrated most recently that amylin is cosecreted with insulin. No data are available on the elimination of amylin from the circulation. We therefore tested plasma levels of amylin, insulin and C-peptide in 49 non-obese, non-diabetic patients (27 male/22 female) with various degree of renal impairment (Group A: CCr less than 20 ml/min, n = 20; Group B: CCr 20-89 ml/min, n = 18; and Group C: CCr greater than 80 ml/min, n = 9). We found a significant increase of plasma amylin when kidney function, expressed by creatinine clearance fell below 20 ml/min (17.9 +/- 1.7 vs. 12.2 +/- 0.8 vs. 8.8 +/- 1.2 pg/ml; p = 0.0005). Plasma amylin correlated closely with serum C-peptide (r = .764; p = 0.0001), and to a lesser extent with insulin (r = .595; p = 0.0001) underlining its postulated cosecretion with these peptides. The data indicate that amylin might be eliminated by renal mechanisms. Our data show that besides type II diabetes mellitus, advanced renal failure is another clinical situation with enhanced plasma amylin levels. Whether amylin plays any pathogenetic role in renal patients remains to be elucidated.

Topics: Amyloid; C-Peptide; Female; Humans; Insulin; Islet Amyloid Polypeptide; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Radioimmunoassay

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Octreotide; Pancreas Transplantation

Disopyramide is a group I antiarrhythmic drug which is mainly used for the treatment of ventricular and supraventricular rhythm disturbances. Commonest side effects result from disopyramide's anticholinergic activity. Other side effects such as hypoglycemia have been reported less frequently. We report one observation of disopyramide induced hypoglycemia, and a review of the literature is presented. Including our observation, 14 cases (9 men and 5 women, aged from 41 to 88) have so far been reported. Doses of disopyramide ranged from 200 to 1,200 mg per day, administered from one day to one year. Symptomatology was mainly neurologic (12 patients) and two patients were clinically asymptomatic. The outcome was favorable in all but the 2 patients who died with persistent hypoglycemia after a single dose of 250 mg in one patient and after 400 mg daily during 4 days in the other (without stopping the drug). Renal function was markedly impaired in 9 patients, two of these patients being on a long term dialysis therapy. Blood levels of disopyramide were measured in 7 patients and ranged from 1 to 11.4 ng/ml. In five patients it was in the normal range (1-4 ng/ml). Three patients were rechallenged for disopyramide: hypoglycemia occurred in all, without clinical symptoms in two of them. The main risk factors of disopyramide induced hypoglycemia are a preexisting chronic renal failure, advanced age, and malnutrition. In these patients normally non toxic disopyramide blood levels, as defined in normal subjects, seem to be inappropriately high. We suggest that in patients at risk, disopyramide blood levels should be maintained at the lower range of therapeutic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Glucose; C-Peptide; Disopyramide; Humans; Hypoglycemia; Insulin; Kidney Failure, Chronic; Male

Eight volunteers with terminal renal insufficiency having consented to the investigation, were given an i.v. bolus administration of 40 pmol biosynthetic human proinsulin on their dialysis-free day. Intravenous blood for the determination of blood glucose proinsulin, insulin and C-peptide was collected in short intervals for 6 hours and thereafter in longer intervals for 24 hours. Proinsulin was determined by immunoradiometric assay with monoclonal antibodies. The proinsulin kinetics were compared with the kinetics of normal volunteers. The behaviour of proinsulin concentration-time is best described with a 3-compartment model. The dominant biological half-life in terminal renal insufficiency was 6.8 hours which signifies a 4.4-fold increase of the normal half-life. The distribution volumes (V1) in the central compartment do not differ in the two groups, whereas the distribution volume after complete distribution (Vss) is significantly increased in renal insufficiency. The total metabolic clearance in renal insufficiency namely 0.63 ml/kg/min is 2.6 times lower compared to normal subjects with 1.67 ml/kg/min. The extra-renal clearance is 39% of the total metabolic clearance rate, whereas the renal clearance comprises 61%. Peripheral conversion from proinsulin to insulin and C-peptide does not occur in terminal renal insufficiency. The basal endogenous proinsulin secretion rate in renal insufficiency does not differ from that of normal volunteers. The following conclusions can be drawn: 1) Hyperinsulinism observed in renal insufficiency can be explained by circulating proinsulin. 2) In the potential therapeutic use of biosynthetic human proinsulin in diabetics with renal insufficiency dosis adjustment according to the remaining renal function would probably be required.

Topics: Adult; Blood Glucose; C-Peptide; Half-Life; Humans; Insulin; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Middle Aged; Proinsulin

The relative importance of renal versus extrarenal mechanisms in the impaired potassium homeostasis in the various stages of chronic renal failure remains undefined. We evaluated potassium homeostasis after an acute oral load of potassium chloride (0.25 mEq/kg body weight) in 10 patients with end-stage renal disease on chronic hemodialysis and 8 control subjects. The maximal increment in plasma potassium concentration in the patients (1.06 +/- 0.13 mEq/1) was significantly higher than that of controls (0.39 +/- 0.1 mEq/1). When expressed as a percentage of the retained load, the patients translocated less potassium into cells (21 vs. 51%). Four of the patients exhibited no apparent transfer of potassium into cells, all the administered load remaining in the extracellular fluid compartment. The extrarenal abnormality does not appear to be related to acidemia, hyperglycemia, or abnormalities in insulin secretion. We conclude that patients with end-stage renal disease undergoing hemodialysis exhibit impaired extrarenal mechanisms of potassium disposal.

Topics: Acid-Base Equilibrium; Administration, Oral; Adult; Blood Glucose; C-Peptide; Female; Homeostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Renal Dialysis

Topics: Blood Glucose; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Triglycerides

Topics: Absorption; Biological Availability; C-Peptide; Glucose; Humans; In Vitro Techniques; Insulin; Kidney Failure, Chronic; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Time Factors

Proinsulin, insulin and C-peptide levels were investigated in chronic renal, hepatic and muscular disorders. The proinsulin levels in human plasma were determined by radioimmunoassay using insulin-degrading enzyme (IDE). The fasting levels of proinsulin in 29 patients with chronic renal failure (0.95 +/- 0.05) were significantly higher than those in 10 patients with liver cirrhosis (0.46 +/- 0.04), six with muscular dystrophy (0.37 +/- 0.02) and 52 normal subjects (0.24 +/- 0.02 ng/ml, mean +/- S.E.). The fasting levels of insulin and C-peptide in chronic renal failure were also the highest among these groups. The insulin levels in liver cirrhosis and muscular dystrophy were significantly greater than those in normal subjects and increased molar ratios of proinsulin to total insulin immunoreactivity in chronic renal failure were observed. These results suggest that the kidney, liver and muscle are related to circulating insulin levels and that the kidney plays a particularly important role in circulating proinsulin levels. It can be concluded that increases in these peptides are due to a hypersecretion of B-cells, a decreased degradation or excretion.

Topics: C-Peptide; Humans; Insulin; Kidney Failure, Chronic; Liver Cirrhosis; Muscular Dystrophies; Proinsulin

A high incidence (40%) of cardiac arrhythmias was found in patients while on dialysis. This incidence was significantly higher than on nondialysis days. A comparison study of patients with significant cardiac arrhythmia and patients with cardiac arrhythmia was made. There was no difference in the echocardiogram, total body potassium, plasma renin activity, aldosterone, catecholamines, serum sodium, potassium and calcium between the two groups. Significant alkalinization occurred in all patients at the end of dialysis. Blood levels of total PTH and C peptide were higher in the arrhythmic patients versus the nonarrhythmic patients. No explanation was found as to why patients developed arrhythmias or what differentiated the two groups.

Topics: Adult; Aged; Arrhythmias, Cardiac; C-Peptide; Calcium; Catecholamines; Echocardiography; Electrocardiography; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Potassium; Renal Dialysis; Renin-Angiotensin System; Sodium

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

The effect of an oral glucose tolerance test (oGTT) on serum levels of branched-chain keto acids (BCKA), i.e. alpha-keto-isocaproic acid (KICA), alpha-keto-isovaleric acid (KIVA) and alpha-keto-beta methyl-n-valeric acid (KMVA) as well as on serum insulin, C-peptide and blood glucose levels was determined in uremic patients and in healthy control subjects. In controls, blood levels of KICA, KMVA and KIVA declined significantly following oral administration of 100 glucose. In uremic patients no decline of KICA was observed. The fall of KMVA was diminished, while suppression of KIVA blood levels in response to the oGGT remained unimpaired. Although serum insulin and C-peptide levels in uremic patients were not significantly different from the controls before and throughout the oGTT, six out of eight displayed abnormal glucose tolerance. It is suggested that the response of blood BCKA levels to an oGTT is altered in uremia, an abnormality restricted primarily to KICA and possibly explained by insulin antagonism and/or by insufficient insulin secretion.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Hemiterpenes; Humans; Insulin; Keto Acids; Kidney Failure, Chronic; Male; Middle Aged; Uremia

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: Adult; Amino Acids, Branched-Chain; Blood Glucose; C-Peptide; Diet; Dietary Proteins; Female; Humans; Insulin; Keto Acids; Kidney Failure, Chronic; Male; Middle Aged; Urea; Uremia

Topics: C-Peptide; Evaluation Studies as Topic; Humans; Kidney Failure, Chronic; Peptides; Polyethylene Glycols; Radioimmunoassay

Topics: Adult; C-Peptide; Estradiol; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Kidney Failure, Chronic; Male; Prolactin; Testosterone; Thyrotropin; Thyrotropin-Releasing Hormone

We have demonstrated persistently elevated serum C-peptide concentrations in patients with chronic renal failure on chronic hemodialysis. A blunted serum C-peptide response to intravenous glucose, glucagon and tolbutamide was also found. However, the response to oral glucose stimulation was greater and more prolonged than in control subjects, probably related to the magnitude of hyperglycemia found in patients with chronic renal failure. These observations suggest the existence of a defect in the renal clearance of C-peptide although an abnormality in C-peptide secretion cannot be excluded.

Topics: Adult; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Pancreas; Peptides

The kidney has been suggested as the main organ for the degradation of C-peptide. This hypothesis was tested in subjects with normal fasting blood glucose concentration and varying degrees of renal failure. Forty-nine subjects with endogenous creatinine clearance ranging from 0--25 ml/min were studied. The basal steady state concentrations of C-peptide (CP) and the immunoreactivity of insulin (IRI) were determined in plasma from fasting patients. The average IRI was similar to that found in normal subjects while a higher CP was found in all patients but two. The average CP in the nephrectomized patients was six times higher than the mean CP in normal subjects (0.35 pmol/ml). There was a significant inverse correlation between clearance and CP (r = 0.51, P less than 0.001) with the highest CP in nephrectomized patients. It is concluded that the increased CP in renal failure, and especially the markedly increased CP in the nephrectomized group supports the hypothesis of the kidney being the organ mainly responsible for the degradation of C-peptide also in man.

Topics: Adult; C-Peptide; Fasting; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Peptides; Uremia

Recently, the radioimmunological determination of C-peptide came into interest because of the jugdement of the remaining function of the islet apparatus in insulin-dependent diabetics. As the degradation of C-peptide preferably takes place in the kidney we performed an intravenous glucose load in 32 patients with kidney diseases. The following results were obtained: 1. In patients with a healthy carbohydrate metabolism a clear correlation exists between the concentration of creatinine on the one hand, the creatinine-clearance and the fasting C-peptide concentration respectively the measured amount of C-peptide on the other hand. 2. The more advanced the renal insufficiency the better is the correlation between the parameter of the kidney function and the C-peptide concentration. 3. In diabetic patients there shows to be no clear correlation between the C-peptide levels and the kidney function. --In insulin-dependent diabetics the amount of C-peptide is only of diagnostic use if the renal function is well known.

Topics: Adult; Aged; C-Peptide; Creatinine; Diabetic Nephropathies; Female; Glucose Tolerance Test; Humans; Islets of Langerhans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Peptides

Topics: Adult; Arginine; C-Peptide; Female; Glucose; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Peptides; Proinsulin; Starvation