c-peptide and Syndrome

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity-associated AN in a 12-year-old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity-associated AN are discussed. In addition, reports of concomitant CRP and obesity-associated AN are reviewed. CRP and obesity-associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity-associated AN. Together with the observation that skin lesions of CRP and obesity-associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.

Topics: Acanthosis Nigricans; Alkaline Phosphatase; Anti-Bacterial Agents; Biopsy; Blood Glucose; C-Peptide; Child; Female; Humans; Insulin Resistance; Minocycline; Obesity; Papilloma; Rare Diseases; Skin; Skin Neoplasms; Syndrome; Treatment Outcome

To compare and assess the single and joint effect of diet and exercise intervention for 1 year on insulin resistance and the development leading toward the insulin resistance syndrome.. An unmasked, randomized 2 x 2 factorial intervention trial was applied with a duration of 1 year for each participant. The trial comprised 219 men and women with diastolic blood pressure of 86-99 mmHg, HDL cholesterol < 1.20 mmol/l, triglycerides > 1.4 mmol/l, total cholesterol of 5.20-7.74 mmol/l, and BMI > 24 kg/m2. Participants were randomly allocated to diet group (n = 35), diet and exercise group (n = 67), exercise group (n = 54), and control group (n = 43). The diet included increased intake of fish and reduced total fat intake. The exercise program entailed supervised endurance exercise three times a week. Baseline cross-sectional changes and 1-year changes in insulin resistance, fasting serum levels of insulin, C-peptide, proinsulin, glucose, and lipids as well as weight, mean blood pressure, and plasminogen activator inhibitor 1 (PAI-1) values were recorded.. The cross-sectional results at baseline showed significant correlations between the calculated insulin resistance and BMI (r = 0.54) and correlations between the mean blood pressure (mBP) (r = 0.26) and PAI-1 (r = 0.40). The 1-year diet intervention gave a significant decrease in the calculated insulin resistance from 4.6 to 4.2 and a positive correlation between the changes in insulin resistance and changes in BMI (r = 0.40). The diet and exercise intervention also led to significantly decreased insulin resistance (from 5.0 to 4.0). The exercise intervention did not significantly change insulin resistance.. The cross-sectional and 1-year intervention results supported each other and underscored the important connection between increased BMI and the development leading toward the insulin resistance syndrome.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol, HDL; Cross-Sectional Studies; Data Interpretation, Statistical; Diet; Exercise; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Life Style; Linear Models; Male; Plasminogen Activator Inhibitor 1; Proinsulin; Statistics, Nonparametric; Syndrome; Triglycerides

Exogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia.. We aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition.. We summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients.. We identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%.. Predisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.

Topics: Autoantibodies; Autoimmune Diseases; C-Peptide; China; Diabetes Mellitus, Type 1; HLA-DRB1 Chains; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Syndrome

The number of case reports of insulin autoimmune syndrome (IAS) induced by methimazole (MMI) is increasing. The purpose of this study is to explore the clinical characteristics and provide a scientific reference for clinical diagnosis, treatment and prevention.. The literature on IAS cases and case series induced by MMI in Chinese and English was collected for retrospective analysis.. A total of 106 patients (males 33, females 73) were described in the Chinese and English literature. The median age of patients with IAS induced by MMI was 37 years (range 15-76) occurring during both regular and irregular MMI therapy or after resumption of medication. The onset of symptoms occurred at night or early morning, within days in some and up to 6 months in others; the symptoms were neuropathic in 65.31% and related to the autonomic nervous system in 33.67%. Blood glucose concentration in samples presumably taken during the hypoglycaemic phase was 1.7 mmol/L (median; range 0.03-4.7); insulin concentrations were elevated ≥100 mU/L (ref range) and associated with low C-peptide levels (<10 μg/L; ref range). Tests for IgG insulin autoantibodies (IAA) were positive in 104 patients (98.02%) and negative in two patients (1.98%). The 75-g oral glucose tolerance test (OGTT) showed impaired glucose tolerance and diabetic curves. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Withdrawal of MMI alone or with corticosteroid treatment reduced hypoglycaemic episodes within days to 3 months. IAA decreased and became negative in 3 months (median; range 1-12). Follow-up showed no recurrent hypoglycaemic episodes at 5 months (median; range 1-60).. Methimazole-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment that should be treated promptly.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoimmune Diseases; Blood Glucose; C-Peptide; Female; Humans; Immunoglobulin G; Insulin; Male; Methimazole; Middle Aged; Syndrome; Young Adult

We investigated the impact of postreperfusion syndrome (PRS) on hyperglycemia occurrence and connecting (C) peptide release, which acts as a surrogate marker for insulin resistance, during the intraoperative period after graft reperfusion in patients undergoing living donor liver transplantation (LDLT) using propensity score (PS)-matching analysis.. Medical records from 324 adult patients who underwent elective LDLT were retrospectively reviewed, and their data were analyzed according to PRS occurrence (PRS vs. non-PRS groups) using the PS-matching method. Intraoperative levels of blood glucose and C-peptide were measured through the arterial or venous line at each surgical phase. Hyperglycemia was defined as a peak glucose level >200 mg/dL, and normal plasma concentrations of C-peptide in the fasting state were taken to range between 0.5 and 2.0 ng/mL.. After PS matching, there were no significant differences in pre- and intra-operative recipient findings and donor-graft findings between groups. Although glucose and C-peptide levels continuously increased through the surgical phases in both groups, glucose and C-peptide levels during the neohepatic phase were significantly higher in the PRS group than in the non-PRS group, and larger changes in levels were observed between the preanhepatic and neohepatic phases. There were higher incidences of C-peptide levels >2.0 ng/mL and peak glucose levels >200 mg/dL in the neohepatic phase in patients with PRS than in those without. PRS adjusted for PS with or without exogenous insulin infusion was significantly associated with hyperglycemia occurrence during the neohepatic phase.. Elucidating the association between PRS and hyperglycemia occurrence will help with establishing a standard protocol for intraoperative glycemic control in patients undergoing LDLT.

Topics: Adult; Blood Glucose; C-Peptide; Female; Humans; Hyperglycemia; Insulin Infusion Systems; Insulin Resistance; Liver Transplantation; Living Donors; Male; Middle Aged; Propensity Score; Reperfusion; Stress, Physiological; Syndrome

Insulin autoimmune syndrome (IAS) is a relatively rare cause of hypoglycemia characterized by endogenous hyperinsulinism and autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. We present a series of IAS cases and describe the clinical characteristics of these cases.. The medical records of inpatients with the final diagnosis of IAS were collected from August 2007 to August 2017 in Peking Union Medical College Hospital. Clinical characteristics and laboratory test results were summarized. The results of serum glucose, insulin, true insulin, and C-peptide testing during 5-h oral glucose tolerance tests were also summarized. Circulating immune complexes were assessed qualitatively by precipitation with polyethylene glycol (PEG) in some patients.. Sixteen patients were included in this study. Insulin autoimmune antibody test results were found positive in 12 patients and weakly positive in 1 patient. Nine patients had an insulin to C-peptide molar ratio >1, whereas 6 patients had an insulin to C-peptide molar ratio <1. Circulating immune complexes were verified in all 4 patients who had been assessed with PEG. During 5-h oral glucose tolerance tests, the C-peptide level responded earlier to the glucose tolerance and had a shorter peak value period compared with insulin, although C-peptide's fluctuation still lagged behind the glucose fluctuation. Three patients presented with self-limited disease courses or limited disease course after discontinuing use of the sulfhydryl group drugs. Some patients' symptoms were relieved after small frequent meals, and some were relieved after taking acarbose. Only 3 patients took glucocorticoids as the anti-immune therapy.. The insulin to C-peptide molar ratios were not consistently >1 in patients with confirmed diagnoses of IAS in our study, which suggested the low sensitivity of insulin to C-peptide molar ratio to detect IAS. The therapy in our study also revealed the self-limited disease course of IAS, and despite the effectiveness of anti-immunity therapy, convenient therapy, such as frequent small meals and adding acarbose, performed well in many patients.

Topics: Acarbose; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; C-Peptide; Child; Female; Glucocorticoids; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Male; Middle Aged; Syndrome; Young Adult

Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia, including surreptitious insulin administration. No standardized treatment regimen exists.. To evaluate an analytic approach to IAS and responses to different treatments.. Observational study in the UK Severe Insulin Resistance Service.. Six patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA).. Glycemia, plasma insulin, and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using ELISA and RIA, and IA were further characterized using radioligand binding studies.. All patients were diagnosed with IAS (five IgG, one IgA) based on a high insulin/C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. One patient was managed conservatively, four were treated with diazoxide without sustained benefit, and four were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis.. IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin/C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.

Topics: Adult; Aged; Autoimmune Diseases; Biomarkers; Blood Glucose; C-Peptide; Chromatography, Gel; Congenital Hyperinsulinism; Diazoxide; Female; Humans; Immunosuppressive Agents; Insulin; Insulin Antibodies; Insulin Resistance; Male; Middle Aged; Syndrome

Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx.. This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate.. We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls.. Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients.. This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

Topics: Adult; Blood Glucose; C-Peptide; Choice Behavior; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Graft Survival; Humans; Hypoglycemia; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreas Transplantation; Retrospective Studies; Risk Assessment; Syndrome; Young Adult

The most common cause of organic fasting hypoglycemia in adults is the presence of an insulin-producing pancreatic adenoma, but when high insulin levels are not found, the differential diagnosis is challenging. Misdiagnosis can lead to an unnecessary pancreatectomy. Insulin concentrations may be low in some cases despite a clinical history suggestive of insulinoma. In these cases, a proinsulinoma should be suspected, although the rarity of this condition requires an extensive workup before reaching a final diagnosis. We describe an unusual case of a 38-year-old man with a severe hypoglycemic syndrome due to a proinsulin-secreting pancreatic adenoma. Insulin was measured by the specific assay and suppressed under the lower detection limit during fasting hypoglycemia. Serum proinsulin and C-peptide levels were abnormally elevated, and further tests revealed an islet cell tumor. The tumor was surgically removed, relieving the fasting hypoglycemia. Histopathological study showed a conventional well-differentiated neuroendocrine tumor with high immunoreactivity against proinsulin and with lesser intensity against insulin. Interestingly, GS-9A8 antibody clone used for immunostaining proinsulin did not cross-react with human insulin or C-peptide, providing an unbiased picture of proinsulin secretion. The resolution of symptoms, the fall of proinsulin concentrations after tumor removal and the histopathology study confirmed the diagnosis of proinsulinoma.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Male; Pancreatic Neoplasms; Proinsulin; Syndrome

Diabetes mellitus is thought to be progressive. Insufficient insulin secretion in compensation for insulin resistance leads to glucose intolerance. A previously reported proband with type A insulin resistance syndrome and her younger twin brothers with and without the R1174W missense mutation in the insulin receptor gene were followed for 9 years to study the progression of glucose metabolism, insulin sensitivity, and β-cell function around puberty. Five-hour OGTT was performed in them at each visit. Areas under the curves of glucose, insulin and C-peptides, insulinogenic index, AIR, and Homa indices were assessed. Intramyocellular lipids (IMCLs) were quantified in the proband and compared to those of 12 nondiabetic subjects, 118 newly diagnosed type 2 diabetic patients. The proband maintained normal HbA1c (27-37 mmol/mol) and fasting plasma glucose (3.7-4.5 mmol/l), and her glucose tolerance ameliorated over years. The proband's Homa-IR decreased into adulthood, while her Homa-B, insulinogenic index, AIR, AUCs of insulin, and C-peptide decreased accordingly. Homa-B to Homa-IR ratios stayed significantly higher than normal. Homa-B, AUCs of insulin, and C-peptide of the twin brothers increased in response to the increment of Homa-IR as they entered middle and late puberty. The changes were more dramatic in the twin brothers carrying the mutation. IMCLs of the proband were lower than those of the nondiabetic counterparts and were disproportional for the degree of insulin resistance. Our longitudinal data of type A insulin resistance syndrome around puberty provide significant information for the study of insulin secretion in compensation for insulin resistance.

Topics: Adolescent; Adult; Amino Acid Substitution; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Lipid Metabolism; Male; Puberty; Receptor, Insulin; Syndrome; Twins; Young Adult

Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin.. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated.. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out.

Topics: Adolescent; Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Diet, Carbohydrate-Restricted; Diet, Diabetic; Female; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Syndrome

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.

Topics: Adult; Antibodies, Antiphospholipid; Autoantibodies; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Glucose Tolerance Test; Glycated Hemoglobin; HLA-DQ alpha-Chains; HLA-DRB1 Chains; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Syndrome

Topics: Aged; Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; China; Diagnosis, Differential; Humans; Hypoglycemia; Immune System; Immunoglobulins; Insulin; Insulin Antibodies; Male; Syndrome

We present the case of a 55 yr female who had recurrent severe hypoglycemic attacks with neuroglycopenic symptoms and altered sensorium including coma. The hypoglycemic episodes were not related to fasting. The hypoglycemia was hyperinsulinemic but all imaging modalities for insulinoma were negative. Selective arterial calcium stimulation test localized the lesion to splenic artery territory and distal pancreatectomy left to the splenic vein was done. The histopathology was consistent with nesidioblastosis and gradient guided pancreatectomy relieved the hypoglycemic episodes.

Topics: Blood Glucose; C-Peptide; Calcium; Female; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Immunohistochemistry; Injections, Intra-Arterial; Insulin; Insulinoma; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Splenectomy; Syndrome; Treatment Outcome

Repeated hypoglycemia is associated with hypoglycemia-associated autonomic failure (HAAF), a syndrome of defective counterregulation.. HAAF increases the risk of severe hypoglycemia in diabetes, although its mechanism remains unresolved. Because beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF.. We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on d 1 would prevent development of HAAF on d 2 in eight nondiabetic subjects (five males, 3 females; age, 28 +/- 3.5 yr; body mass index, 24.2 +/- 2.1 kg/m(2)). On four occasions, d 1 was: 1) two 90-min hypoglycemic clamps (N-); 2) two 90-min hypoglycemic clamps plus naloxone (N+); 3) two euglycemic 90-min clamps (C); or 4) two euglycemic 90-min clamps plus naloxone (C+).. Day 1 hypoglycemia caused marked deterioration of d 2 hormonal responses to hypoglycemia, consistent with HAAF-i.e. decreased plasma epinephrine, norepinephrine, and glucagon compared to control (C) (374 +/- 71 vs. 810 +/- 94, 307 +/- 65 vs. 686 +/- 98, and 71 +/- 9 vs. 93 +/- 4 pg/ml, respectively, P < 0.01), as well as in endogenous glucose production (24 vs. 163%; P < 0.01). In contrast, naloxone on d 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852 +/- 82, 769 +/- 77, and 98 +/- 7 pg/ml) and endogenous glucose production recovery (167%) were identical to those after d 1 euglycemia (P < NS for all). Infusion of naloxone alone during euglycemia on d 1 (C+) had no effect on d 2 responses.. These data suggest that the opioid signaling system is a promising target for further studies to prevent HAAF.

Topics: Adult; Autonomic Nervous System Diseases; beta-Endorphin; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Gluconeogenesis; Humans; Hypoglycemia; Insulin; Male; Naloxone; Narcotic Antagonists; Norepinephrine; Receptors, Opioid; Syndrome

Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease.. Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests.. All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation.. Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.

Topics: Adult; Aged; Amyloid; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; C-Peptide; Cell Proliferation; Diazoxide; Fasting; Female; Homeodomain Proteins; Humans; Hyperinsulinism; Hypoglycemia; Immunohistochemistry; Insulin; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Lectins, C-Type; Male; Middle Aged; Nesidioblastosis; Pancreatectomy; Pancreatitis-Associated Proteins; Postprandial Period; Proinsulin; Receptors, Calcium-Sensing; Syndrome; Trans-Activators

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

A 53-year-old Caucasian woman presented with repeated episodes of hypoglycemia. Self-monitored blood glucose levels during the attacks were between 40 and 60 mg/dl (2.2-3.3 mmol/l).. An oral glucose tolerance test performed over 210 minutes showed normal baseline glucose levels, markedly elevated levels of serum insulin and slightly elevated C-peptide concentrations. During the test, a marked increase of insulin and a normal increment of C-peptide were observed. The tentative diagnosis of an insulinoma was raised and a 72 h fasting test performed, throughout which the insulin-glucose-ratio was pathologically elevated, whereas C-peptide levels were only slightly elevated.. Strongly positive levels of insulin antibodies led to the diagnosis of an insulin autoimmune syndrome.. This syndrome is caused by IgG-insulin-complexes with prolonged plasma half-life in the presence of reduced insulin action. The therapy consisted of fractionated meals to avoid hyperinsulinism and following hypoglycemic episodes. After four months a spontaneous clinical remission was observed.. The autoimmune insulin syndrome is a rare cause of recurrent, spontaneous hypoglycemia in Europe in non diabetic patients. Its prognosis is good as there is a high rate of spontaneous clinical remission in up to 80 % of patients.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Immunoglobulin G; Insulin; Insulin Antibodies; Middle Aged; Prognosis; Remission, Spontaneous; Syndrome

Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America.. A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

Topics: Autoimmune Diseases; C-Peptide; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Antibodies; Male; Middle Aged; Syndrome

Topics: Aged; Analgesics, Non-Narcotic; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; C-Peptide; Carbamazepine; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Eruptions; Female; Herpesviridae Infections; Herpesvirus 6, Human; Humans; Insulin; Insulin Secretion; Syndrome

In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic beta-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium channel responsible for glucose-induced insulin secretion. Four patients who underwent gradient-guided partial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has had brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in the absence of insulinoma may constitute a new syndrome of postprandial hypoglycemia from diffuse beta-cell hyperfunction.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Calcium; Female; Glycosyltransferases; Humans; Hyperinsulinism; Hypoglycemia; Islets of Langerhans; Male; Membrane Proteins; Mutation; Pancreas; Pancreatectomy; Postprandial Period; Potassium Channels; Potassium Channels, Inwardly Rectifying; Regional Blood Flow; Repressor Proteins; Saccharomyces cerevisiae Proteins; Syndrome; Tomography, X-Ray Computed; Ultrasonography

We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.

Topics: Antithyroid Agents; Autoantibodies; Autoimmune Diseases; C-Peptide; Carbimazole; Humans; Hyperthyroidism; Hypoglycemia; Insulin; Japan; Male; Middle Aged; Morocco; Paris; Propylthiouracil; Syndrome; White People

The effects of cigarette smoking on insulin resistance, postprandial lipemia following a mixed meal, lipoproteins and other aspects of the insulin resistance syndrome (IRS) were investigated in healthy middle-aged men.. 36 smoking and 25 age- and body mass index (BMI)-matched non-smoking men participated. They were non-obese (BMI < 27), healthy and without any medication. The smokers had been smoking more than 10 cigarettes per day for more than 20 years; the non-smokers had never been habitual smokers. Body composition and several metabolic and cardiovascular risk factors were studied, including the prevalence of small dense LDL-particles, lipoprotein and hepatic lipase activity and triglyceride levels after a mixed test meal. For determination of degree of insulin sensitivity the euglycemic hyperinsulinemic clamp technique was used.. The smokers had lower HDL-cholesterol and lipoprotein A-I levels but higher fasting triglycerides, as well as an increased proportion of small dense LDL-particles and higher postheparin hepatic lipase activity. They also had higher levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1) activity and fasting and steady-state C-peptide levels during the clamp. The smokers were insulin resistant and lipid intolerant with an impaired triglyceride clearance after a mixed test meal. This lipid intolerance was not mirrored by fasting hypertriglyceridemia.. This study, using the euglycemic hyperinsulinemic clamp technique, shows that smokers are both insulin resistant and lipid intolerant. The postprandial lipid intolerance is also seen in individuals with normal fasting triglyceride levels and is related to an increased prevalence of atherogenic small dense LDL. IRS is likely to be an important reason for the increased cardiovascular morbidity in smokers.

Topics: Adult; Apolipoprotein A-II; Apolipoproteins B; Blood Glucose; Body Mass Index; C-Peptide; Fibrinogen; Glucose Clamp Technique; Humans; Insulin Resistance; Lipids; Lipoprotein Lipase; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Postprandial Period; Radioimmunoassay; Risk Factors; Smoking; Syndrome; Uric Acid

Topics: Acanthosis Nigricans; C-Peptide; Female; Humans; Hyperinsulinism; Insulin Resistance; Lupus Erythematosus, Systemic; Middle Aged; Syndrome

To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians.. A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity.. Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation.. This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.

Topics: Adult; Asian; Body Constitution; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Fasting; Female; Hawaii; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Prevalence; Risk Factors; Sex Characteristics; Syndrome

Topics: Acanthosis Nigricans; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Syndrome

The examination of 40 patients with generalized lipodystrophy elucidated the dependence of the severity of cardiovascular disorders in these patients on the immunoreactive insulin/C-peptide index. In high values of the latter cardiovascular disorders occur more frequently. The role of insulin in pathogenesis of essential hypertension, chronic IHD is assessed.

Topics: Adolescent; Adult; C-Peptide; Cardiovascular Diseases; Coronary Disease; Humans; Hypertension; Insulin; Lipodystrophy; Middle Aged; Risk Factors; Syndrome

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's minimal model (intravenous glucose in combination with tolbutamide) and systolic blood pressure (SBP) was measured with a London School of Hygiene Sphygmomanometer. A number of anthropometric measurements including body mass index (BMI, kilograms/meters squared) and biochemical characteristics were performed. The Lewis blood group typing was carried out on erythrocytes. Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165), the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015), fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029), and plasma glucose (8%, P = .003). The fasting values of serum lipids, plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men with other Lewis phenotypes. Altogether 194 women participated in the study of which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity (45%, P = .044), no values differed between Le(a-b-) women and women with other Lewis phenotypes. The women were also stratified according to use of oral contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA antigen (P = .004) compared to women using oral contraceptives without the Le(a-b-) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit features of the insulin resistance syndrome, including higher levels of BMI, SBP, and fasting levels of serum insulin and plasma glucose. In young women no signs of the insulin resistance syndrome were found in subjects with the Le(a-b-) phenotype.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cardiovascular Diseases; Female; Genetic Markers; Humans; Insulin; Insulin Resistance; Lewis Blood Group Antigens; Life Style; Male; Risk Factors; Sex Factors; Syndrome

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

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

The secretion of hormones stimulating and inhibiting gastric secretory activity was studied in 85 patients with postvagotomy syndromes. The somatropin level was found to increase significantly in gastrostasis. The lower values of the blood insulin and C-peptide content in patients with recurrent ulcers was evidently associated either with insufficiency of the pancreatic insular apparatus or with partial vagal denervation, increased STH level, and plausible inhibiting effect of glucagon. Increased somatostatin secretion in the dumping syndrome, gastrostasis, and peptic ulcers may be due to the encountered hypergastrinemia.

Topics: C-Peptide; Constriction, Pathologic; Diarrhea; Dumping Syndrome; Gastric Acid; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Neurotransmitter Agents; Peptic Ulcer; Postoperative Complications; Recurrence; Somatostatin; Stomach Diseases; Syndrome; Vagotomy, Proximal Gastric

Patients with microvascular angina (syndrome X) may be insulin resistant. We designed a study to establish whether this is the case. 11 patients with microvascular angina were compared with 9 matched subjects with noncardiac chest pain. Patients and controls were evaluated by coronary sinus catheterisation, and by isotopic measurement of glucose turnover, indirect calorimetry, and forearm technique during a 3 h baseline period after overnight fast and during a 2 h hyperinsulinaemic euglycaemic clamp. Pace-induced increase in coronary sinus blood flow was less in patients than in controls, whereas forearm blood flow did not differ between groups. Baseline measures of glucose metabolism were normal. During the clamp, glucose production and lipolysis were equally suppressed in both groups. Mean (SE) total insulin-induced glucose uptake was significantly impaired in patients compared with controls (3.9 [0.7] vs 6.4 [0.7] mg/kg per min; p < 0.01), and insulin-stimulated glucose uptake in the forearm was significantly reduced in patients (0.88 [0.10] vs 1.6 [0.30] mmol/L; p < 0.001). Reduced oxidative and nonoxidative metabolism accounted for the defect in overall glucose uptake in patients. No correlation between changes in coronary sinus blood flow and total body glucose uptake was seen. We found that microvascular angina was associated with substantial insulin resistance. Whether this relation is causal or coincidental is as yet unsettled.

Topics: Alanine; Angina Pectoris; Basal Metabolism; Blood Glucose; C-Peptide; Chest Pain; Coronary Circulation; Energy Metabolism; Fatty Acids, Nonesterified; Female; Forearm; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Growth Hormone; Humans; Insulin; Insulin Resistance; Lactates; Male; Microcirculation; Middle Aged; Regional Blood Flow; Syndrome

To investigate the relationship between the pituitary-adrenocortical function, abdominal obesity, and insulin resistance syndrome.. A prospective study.. Helsinki University Hospital, Finland.. Sixty-six healthy males aged 30-55 years.. Insulin, C-peptide, cortisol and ACTH responses during the oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone suppression and intravenous adrenocorticotrophic hormone (ACTH) stimulation.. The subjects in the highest tertile of the waist-to-hip ratio (WHR) had lower high-density lipoprotein cholesterol (HDLC) (P < 0.05), but higher triglyceride (TG), insulin, and C-peptide levels, ACTH response to glucose at 2 h, and cortisol response to ACTH (P < 0.01) than those in the lowest tertile. The cortisol response to ACTH correlated positively, but cortisol levels during the OGTT correlated negatively with WHR. The ratio of these cortisol determinations correlated positively with the body-mass index (BMI) (r = 0.554; P < 0.001), WHR (r = 0.536; P < 0.001), TG (r = 0.397; P = 0.001), fasting insulin (r = 0.534; P < 0.001) and C-peptide (r = 0.458; P < 0.001), and negatively with HDLC (r = 0.353; P = 0.004). In multiple regression analyses, BMI and the 2-h ACTH response to glucose were significant predictors of WHR and, in addition, the cortisol ratio, WHR, and BMI of insulin.. Abdominal obesity may be associated with subtle central adrenal insufficiency, which might also affect insulin and lipoprotein metabolism.

Topics: Abdomen; Adrenocorticotropic Hormone; Adult; Blood Glucose; Body Mass Index; C-Peptide; Humans; Hydrocortisone; Insulin; Insulin Resistance; Linear Models; Lipids; Male; Middle Aged; Obesity; Syndrome

Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100 mU/kg.min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Cholesterol; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Resistance; Lipodystrophy; Syndrome; Triglycerides

Glucose and insulin responses to a glucose load in 11 patients with angina attributed to microvascular coronary dysfunction were compared with those in 11 healthy subjects matched for age, sex, and body mass. Stimulated hyperinsulinaemia was demonstrated in the microvascular angina group. The findings suggest a role for increased concentrations of insulin in coronary microvascular dysfunction.

Topics: Adult; Angina Pectoris; Blood Glucose; C-Peptide; Coronary Circulation; Evaluation Studies as Topic; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Male; Microcirculation; Middle Aged; Syndrome

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Female; Growth Hormone; Humans; Hyperglycemia; Insulin Resistance; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Kinetics; Recombinant Proteins; Syndrome

A 43-year-old woman with spontaneous episodes of neuroglycopenic hypoglycemia was found to have immune-mediated thrombocytopenic purpura and primary biliary cirrhosis. Hypoglycemia along with hyperinsulinemia suggested insulinoma. Serum c-peptide levels were disproportionately low, raising the possibility of factitious hypoglycemia. The patient's plasma contained circulating insulin receptor autoantibodies, thought to cause hypoglycemia by their insulin-like actions. With prednisone therapy, her other autoimmune features improved, and the hypoglycemia eventually resolved. Hypoglycemia mediated by insulin receptor autoantibodies should be considered in patients with fasting hypoglycemia and features suggesting an underlying autoimmune disorder before pursuing more invasive procedures. High-dose steroids may be life-saving in this disorder.

Topics: Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Diagnosis, Differential; Fasting; Female; Humans; Hypoglycemia; Insulin; Liver Cirrhosis, Biliary; Prednisone; Receptor, Insulin; Syndrome; Thrombocytopenia

The results of puncture biopsy of the liver, ultrasonic and angiographic investigation of the liver and pancreas in 114 patients with chronic alcoholism revealed an increment of changes in these organs in parallel with an increase in the duration of chronic alcoholic intoxication. A simultaneous study of immunoreactive insulin (IRI) and C-peptide showed that an increase in the IRI basal level in the patients suffering from alcoholism up to 10 yrs was determined mainly by an increase in the activity of beta-cells. In a long period of alcoholism an increase in the IRI basal level resulted from a decrease in the rate of insulin degradation in the liver as assessed by a lower level of C-peptide. In liver cirrhosis a noticeable decrease in pancreatic incretory function was combined with noticeable disturbance of insulin degradation in the liver. The above investigations showed that there were morphological, functional and clinical signs of the "hepatopancreatic syndrome" in chronic alcoholism.

Topics: Adult; Alcoholism; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Liver Diseases, Alcoholic; Male; Middle Aged; Pancreatic Diseases; Syndrome; Time Factors

Topics: Adolescent; Autoantibodies; C-Peptide; Female; Glucose Tolerance Test; Graves Disease; Humans; Insulin Antibodies; Methimazole; Syndrome

We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.

Topics: Adult; Aged; Amino Acid Sequence; Animals; C-Peptide; Chromatography, High Pressure Liquid; Dogs; Female; Half-Life; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Pedigree; Rats; Receptor, Insulin; Syndrome

Topics: Adult; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Muscular Dystrophies; Syndrome

A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2-3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23-0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.

Topics: Acanthosis Nigricans; Adolescent; Arginine; C-Peptide; Diabetes Complications; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Resistance; Islets of Langerhans; Male; Proinsulin; Receptor, Insulin; Syndrome

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.

Topics: C-Peptide; Celiac Disease; Cholelithiasis; Diabetes Complications; Glucagon; Hormones, Ectopic; Humans; Hypothalamus; Islets of Langerhans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Pituitary Gland; Radioimmunoassay; Somatostatin; Syndrome

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Peptides; Syndrome

A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies were also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 nk, at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 micron U./ml. was registered at 180 minutes, while the peak value of free IRI of 208 micronU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 X 10(9)M-1). Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemic attack in the patient. The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.

Topics: Adult; Antibodies; Antigens; Autoimmune Diseases; C-Peptide; Chromatography, Gel; Female; Glucose; Humans; Hypoglycemia; Infusions, Parenteral; Insulin; Syndrome