c-peptide and Chronic-Disease

Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes.. A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment.. In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed.. The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

Topics: Adolescent; Antibodies, Monoclonal; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Humans; Insulin

Type 1 diabetes is a chronic disease characterized by progressive destruction of the pancreatic beta cells, what leads to insulin deficiency and hyperglycemia. However, a significant secretory function may persist for long periods in a few patients, what is clinically evident through the detection of serum C peptide. This phenomenon might reduce the risk of chronic complications, severe hypoglycemias and allow easier metabolic control. It is possible that these advantages are caused, at least partially, by C peptide itself, acting directly in its target tissues.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Child; Child, Preschool; Chronic Disease; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Young Adult

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

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

Topics: Adolescent; Adult; Antibodies, Monoclonal, Humanized; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin-Secreting Cells; Interleukin-1beta; Middle Aged; Young Adult

We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function.. We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site's C-peptide concentration and kinetics, we differentiated insulin secreted from the individual's native pancreatic beta cells and that secreted from allografted beta cells.. Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small.. Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Female; Hepatic Veins; Humans; Immunosuppressive Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Portal Vein; Regeneration; Transplantation, Homologous

The vascular endothelium is a site of pathological changes in patients with diabetes mellitus that may be related to severe chronic hyperglycemia. However, it is unclear whether transient hyperglycemia alters vascular function in an otherwise healthy human forearm. To test the hypothesis that acute, moderate hyperglycemia impairs endothelium-dependent forearm vasodilation, we measured vasodilator responses in 25 healthy volunteers (11 F, 14 M) assigned to one of three protocols. In protocol 1, glucose was varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance. Protocol 2 involved 6 h of mild hyperglycemia (approximately 7 mmol/l). Protocol 3 involved 6 h of euglycemia. Glucose concentration was maintained with a variable systemic glucose infusion. Insulin concentrations were maintained at approximately 65 pmol/l by means of a somatostatin and "basal" insulin infusion. Glucagon and growth hormone were replaced at basal concentrations. Forearm blood flow (FBF) was calculated from Doppler ultrasound measurements at the brachial artery. In each protocol, FBF dose responses to intrabrachial acetylcholine (ACh) and sodium nitroprusside (NTP) were assessed at baseline and at 60, 180, and 360 min of glucose infusion. Peak endothelium-dependent vasodilator responses to ACh were not diminished by hyperglycemia in any trial. For example, peak responses to ACh during protocol 2 were 307 +/- 47 ml/min at euglycemic baseline and 325 +/- 52, 353 +/- 65, and 370 +/- 70 ml/min during three subsequent hyperglycemic trials (P = 0.46). Peak endothelium-independent responses to NTP infusion were also unaffected. We conclude that acute, moderate hyperglycemia does not cause short-term impairment of endothelial function in the healthy human forearm.

Topics: Adaptation, Physiological; Adolescent; Adult; Blood Flow Velocity; Blood Glucose; Brachial Artery; C-Peptide; Chronic Disease; Female; Forearm; Glucose Clamp Technique; Hemostasis; Humans; Hyperglycemia; Insulin; Male; Metabolic Clearance Rate; Regional Blood Flow; Ultrasonography

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

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

The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20-120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m(2)); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1alpha gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All participants underwent three hyperglycemic clamps (2 h, 15 mM) with continuous infusion of saline, 1 pmol GLP-1 (7-36)amide/kg body weight.min or 4 pmol GIP pmol/kg body weight.min. The early-phase (0-20 min) plasma insulin response tended to be enhanced by both GIP and GLP-1, compared with glucose alone, in all five groups. In contrast, the late-phase (20-120 min) plasma insulin response to GIP was attenuated, compared with the plasma insulin response to GLP-1, in all five groups. Significantly higher glucose infusion rates were required during the late phase of the GLP-1 stimulation, compared with the GIP stimulation. In conclusion, lack of GIP amplification of the late-phase plasma insulin response to glucose seems to be a consequence of diabetes mellitus, characterizing most, if not all, forms of diabetes.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Male; Middle Aged; Neurotransmitter Agents; Nuclear Proteins; Pancreatitis; Peptide Fragments; Phenotype; Protein Precursors; Transcription Factors

To assess the safety and efficacy of islet autotransplantation (IAT) combined with total pancreatectomy (TP) to prevent diabetes.. There have been recent concerns regarding the safety of TP and IAT. This is thought to be related to the infusion of large volumes of unpurified pancreatic digest into the portal vein. Minimizing the volume of islet tissue by purifying the pancreatic digest has not been previously evaluated in terms of the postoperative rate of death and complications, pain relief, and insulin independence.. During a 54-month period, 24 patients underwent pancreas resection with IAT. Islets were isolated using collagenase and a semiautomated method of pancreas digestion. Where possible, islets were purified on a density gradient and COBE processor. Islets were embolized into the portal vein, within the spleen and portal vein, or within the spleen alone. The total median volume of digest was 9.9 mL.. The median number of islets transplanted was 140,419 international islet equivalents per kilogram. The median increase in portal pressure was 8 mmHg. Early complications included duodenal ischemia, a wedge splenic infarct, partial portal vein thrombosis, and splenic vein thrombosis. Intraabdominal adhesions were the main source of long-term problems. Eight patients developed transient insulin independence. Three patients were insulin-independent as of this writing. Patients had significantly decreased insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. Of the patients alive and well as of this writing, four had failed to gain relief of their abdominal pain and were still opiate-dependent.. Combined TP and IAT can be a safe surgical procedure. Unfortunately, almost all patients were still insulin-dependent, but they had decreased daily insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. A prospective randomized study is therefore needed to assess the long-term benefit of TP and IAT on diabetic complications.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; England; Female; Humans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Pancreatitis; Postoperative Complications; Prospective Studies; Statistics, Nonparametric

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

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

An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo results have been disputed because the amelioration of insulin action that follows sulfonylurea may represent the relief from glucose toxicity rather than a direct effect of the drug. Therefore, we studied the hypoglycemic action of gliclazide acutely and after 2 months of therapy in seven type 2 diabetic patients. All patients received a 240-minute i.v. glucose infusion with [3-3H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study 2) was given orally before glucose infusion. Finally, the effect of 160 mg gliclazide was reassessed after a two-month treatment with the same sulfonylurea (80 mg t.i.d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose production (EGP) were similar before the two initial studies. During glucose infusion, EGP was more suppressed after gliclazide in spite of comparable increase in plasma insulin and C-peptide. After the two-month therapy, basal plasma glucose levels and HbA1c were lower while plasma insulin and C-peptide were higher with respect to baseline (p < 0.05). Gliclazide further reduced plasma glucose, the incremental area above baseline, and EGP during glucose infusion, while plasma insulin and C-peptide achieved higher plateaus (p < 0.05). When data were pooled, plasma glucose concentration and EGP correlated both in the basal state (r = 0.71) and during the last hour of glucose infusion (r = 0.84; both p < 0.05). These data suggest that gliclazide enhances the suppression of EGP induced by insulin and that this effect is greater with chronic treatment because of concomitant improvement of insulin secretion.

Topics: Acute Disease; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Gliclazide; Gluconeogenesis; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Kinetics; Middle Aged; Placebos; Regression Analysis; Time Factors; Tritium

Insulin-like growth factor I (IGF-I) enhances myofibrillar development in cardiomyocytes of rats in culture and in vivo. In addition, IGF-I has vasodilatory effects and improves cardiac function in healthy volunteers. This study was conducted to evaluate the acute hemodynamic effects of IGF-I in patients with chronic heart failure Eight patients with chronic heart failure were randomized to receive recombinant human IGF-I (60 micrograms/kg) or placebo, i.v., over 4 h in a cross-over, double blind study on 2 consecutive days. Electrocardiogram as well as systemic hemodynamics were continuously monitored over 7 h by flow-guided thermodilution and radial artery catheters. IGF-I was well tolerated by all patients, and no pathological changes on electrocardiogram were recorded. Compared with placebo, IGF-I increased the cardiac index by 27 +/- 3.7% (+/- SE; P < 0.0005) and the stroke volume index by 21 +/- 5.6% (P < 0.05), and decreased systemic vascular resistance by 28 +/- 4.4% (P < 0.0002), right atrial pressure by 33 +/- 9.0% (P < 0.003), and pulmonary artery wedge pressure by 25 +/- 6.1% (P < 0.03). Mean systemic and pulmonary artery pressure as well as heart rate and pulmonary vascular resistance were not significantly influenced by IGF-I treatment. Insulin and C peptide levels were decreased by IGF-I, whereas glucose and electrolyte levels remained unchanged. Urinary levels of norepinephrine decreased significantly (P < 0.05) during IGF-I infusion. Thus, acute administration of IGF-I in patients with chronic heart failure is safe and improves cardiac performance by afterload reduction and possibly by positive inotropic effects. Further investigations to establish whether the observed acute effects of IGF-I are maintained during chronic therapy appear to be warranted.

Topics: Adult; C-Peptide; Cardiomyopathy, Dilated; Cardiovascular System; Chronic Disease; Cross-Over Studies; Double-Blind Method; Female; Hemodynamics; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Myocardial Ischemia; Placebos; Recombinant Proteins; Vascular Resistance

The aim of the study was to evaluate the function of pancreatic the B-cell and carbohydrate tolerance after and during pancreatitis. Forty patients (30 men and 10 women) in mean age 41.6 +/- 11.6 years (mean +/- SD) were studied. Analysis of the results was performed in four groups: 1) normal controls, 2) patients after biliary acute pancreatitis (AP) in anamnesis, 3) patients with chronic pancreatitis (ChP) and normal carbohydrate tolerance and 4) patients with chronic pancreatitis and impaired of glucose tolerance (ChP + IGT, WHO classification). Pancreatitic B-cell activity was evaluated by the measurement insulin (IRI) and C-peptide (CP) serum concentrations in fasting state and after 75 g oral glucose and after intravenous glucagon injection (1 mg). Hepatic insulin extraction was estimated from of the serum IRI/CP molar ratio. This study demonstrated impaired function of the pancreatic B-cell in groups after acute pancreatitis and with chronic pancreatitis at normal levels of glycaemia. A progressive reduction of stimulated serum IRI and CP concentrations in groups (2), (3) and (4) was observed. In those groups the increase of serum IRI/CP ratio was found.. Impaired function of the B-cell after pancreatitis is a frequent complication and to improve metabolic control a mechanism of hepatic insulin clearance reduction is involved.

Topics: Adult; C-Peptide; Chronic Disease; Dietary Carbohydrates; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Pancreatitis

The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Glucagon; Humans; Insulin; Pancreatic Function Tests; Pancreatic Polypeptide; Pancreatin; Pancreatitis

Therapeutic pancreatic duct occlusion (PDO) is applied to preserve endocrine pancreatic function by atrophizing and thus eliminating chronically inflamed exocrine pancreatic parenchyma. So far, efficient and lasting elimination of exocrine parenchyma is brought about only by intraoperative PDO upon partial duodenopancreatectomy. While partial duodenopancreatectomy itself reduces endocrine pancreatic function by about 40%, intraoperative PDO does not further impair endocrine function. Endocrine function is not affected at all by endoscopic PDO, which has to be improved, however, concerning its eliminatory effect on exocrine pancreatic parenchyma.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diatrizoate; Drug Combinations; Endoscopy; Fatty Acids; Follow-Up Studies; Humans; Insulin; Isoamylase; Lipase; Pancreatectomy; Pancreatic Ducts; Pancreatic Function Tests; Pancreatic Pseudocyst; Pancreatitis; Postoperative Complications; Propylene Glycols; Proteins; Trypsin; Zein

Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing β-cell autoimmunity in susceptible individuals.. We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy.. All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis.. These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of β-cell antigens and neoepitope generation, which are potential initiating events for loss of β-cell self-tolerance.

Topics: Acute Disease; Adolescent; Adult; Autoantibodies; C-Peptide; Child; Child, Preschool; Chronic Disease; Diabetes Mellitus, Type 1; Humans; Infant; Inflammation; Middle Aged; Pancreatitis; Protein Processing, Post-Translational; Recurrence; Risk Factors; Young Adult

During pregnancy, maternal stressors cause changes in both maternal and fetal HPA axes. We therefore investigated the impact of maternal non chronic and chronic stress on fetal glucose metabolism and growth, and serum levels of cortisol in the fetus.. Normal weight pregnant women (n = 192; mean ± SD 27.9 ± 4.2 years old, and; 26.9 ± 2.4 kg/m²) were assessed during the 2nd and 3rd trimester with anthropometry, fetal ultrasound, blood samples for serum CRH, cortisol and IL6, and STAI trait and state stress questionnaires. We measured serum cortisol, insulin and c-peptide, and plasma glucose from cord blood. Neonates underwent anthropometry at the 3rd post-delivery day.. In both 2nd and 3rd trimesters, women with STAI trait scores ≥40 had significantly greater levels of fasting serum CRH and cortisol than those with STAI trait scores<40. 2nd trimester: STAI trait scores correlated positively with cord blood glucose and c-peptide. Maternal serum CRH correlated negatively with U/S fetal biparietal head diameter, while serum cortisol correlated positively with abdominal circumference. Maternal serum IL6, CRH and cortisol all correlated positively with birth waist circumference. 3rd trimester: Women with STAI state scores ≥40 had fetuses with larger U/S abdominal and smaller head circumferences compared to those of women with STAI scores <40. Women with STAI trait scores ≥40 had greater levels of cord blood cortisol, glucose, and c-peptide compared to women with STAI scores <40. STAI state scores ≥40 correlated positively with maternal CRH and U/S fetal abdominal circumference, and negatively with fetal head circumference and biparietal diameter. STAI trait scores correlated positively with cord blood c-peptide, glucose, insulin and cortisol. Maternal serum levels of CRH correlated positively with U/S fetal abdominal circumference and cord blood cortisol, and negatively with fetal head circumference and biparietal head diameter. Maternal serum levels of both CRH and cortisol correlated positively with cord blood c-peptide, glucose, and insulin. STAI trait was the best positive predictor of cord blood cortisol, glucose and c-peptide, whilst STAI state was the best positive and negative predictor, respectively of fetal abdominal circumference and fetal head circumference or biparietal diameter.. Increased maternal chronic stress (reflected by the STAI trait score) associates with increased fetal cortisol, glucose, c-peptide secretion and thus, insulin resistance. Maternal non chronic stress (STAI state) in the 3rd trimester associates with changes in fetal growth pattern, including increased and decreased measurements of fetal abdominal and head growth respectively.

Topics: Adult; Blood Glucose; Body Size; C-Peptide; Chronic Disease; Female; Fetal Blood; Fetal Development; Humans; Hydrocortisone; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Stress, Psychological; Ultrasonography, Prenatal; Waist Circumference; Young Adult

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

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

To assess the outcomes of drug therapy (DT) followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.. DT comprised of pancreatic enzymes and anti-oxidants failing which, endotherapy (ET; pancreatic sphincterotomy and stent placement) was done. The frequency of pain, its visual analogue score (VAS), quality of life (QoL), serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET. Response was defined as at least 50% reduction in the severity of pain to below a score of 5.. Of the thirty nine patients analysed, 21 (53.9%) responded to DT and 18 (46.1%) underwent ET. The VAS for pain (7.0 ± 2.0. A standardised protocol of DT, followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis, enhanced QoL and improved pancreatic function.

Topics: Acute Disease; Adolescent; Adult; Antioxidants; C-Peptide; Child; Chronic Disease; Feces; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Pain Management; Pain Measurement; Pancreas; Pancreatitis; Prospective Studies; Quality of Life; Recurrence; Sphincterotomy, Endoscopic; Young Adult

Dogs consuming a hypercaloric high-fat and -fructose diet (52 and 17% of total energy, respectively) or a diet high in either fructose or fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) and glycogen deposition in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery. The effect of a hypercaloric diet containing neither fructose nor excessive fat has not been examined. Dogs with an initial weight of ≈25 kg consumed a chow and meat diet (31% protein, 44% carbohydrate, and 26% fat) in weight-maintaining (CTR; n = 6) or excessive (Hkcal; n = 7) amounts for 4 wk (cumulative weight gain 0.0 ± 0.3 and 1.5 ± 0.5 kg, respectively, P < 0.05). They then underwent clamp studies with infusions of somatostatin and intraportal insulin (4× basal) and glucagon (basal). The hepatic glucose load was doubled with peripheral (Pe) glucose infusion for 90 min (P1) and intraportal glucose at 4 mg·kg(-1)·min(-1) plus Pe glucose for the final 90 min (P2). NHGU was blunted (P < 0.05) in Hkcal during both periods (mg·kg(-1)·min(-1); P1: 1.7 ± 0.2 vs. 0.3 ± 0.4; P2: 3.6 ± 0.3 vs. 2.3 ± 0.4, CTR vs. Hkcal, respectively). Terminal hepatic glucokinase catalytic activity was reduced nearly 50% in Hkcal vs. CTR (P < 0.05), although glucokinase protein did not differ between groups. In Hkcal vs. CTR, liver glycogen was reduced 27% (P < 0.05), with a 91% increase in glycogen phosphorylase activity (P < 0.05) but no significant difference in glycogen synthase activity. Thus, Hkcal impaired NHGU and glycogen synthesis compared with CTR, indicating that excessive energy intake, even if the diet is balanced and nutritious, negatively impacts hepatic glucose metabolism.

Topics: Animals; Blood Glucose; C-Peptide; Chronic Disease; Dogs; Eating; Glucose; Glucose Clamp Technique; Hyperphagia; Insulin; Liver; Male; Weight Gain

This study evaluated the association between serum C-peptide levels and chronic vascular complications in Korean patients with type 2 diabetes. Data for 1,410 patients with type 2 diabetes were evaluated cross-sectionally. Fasting and postprandial 2-hour serum C-peptide levels were analyzed with respect to diabetic micro- and macrovascular complications. In the group of patients with lower fasting serum C-peptide quartile, the prevalences of diabetic retinopathy and neuropathy were significantly higher (P = 0.035, P < 0.001, respectively). In the group of patients with lower delta C-peptide (postprandial - fasting C-peptide) quartile, the prevalences of diabetic retinopathy, nephropathy, and neuropathy were significantly higher (P < 0.001 for all). Low delta C-peptide quartile was also associated with increased severity of retinopathy and nephropathy. The age- and sex-adjusted odds ratios (ORs) for retinopathy, neuropathy, and nephropathy in the lowest versus the highest delta C-peptide quartile were 6.45 (95% confidence interval 3.41-12.22), 3.01 (2.16-4.19), and 2.65 (1.71-4.12), respectively. After further adjustment for the duration of diabetes, type of antidiabetic therapy, mean hemoglobin A1c, body mass index, and blood pressure, the ORs were reduced to 2.83 (1.32-6.08), 1.68 (1.12-2.53), and 1.61 (1.05-2.47), respectively, but remained significant. No significant difference was observed in the prevalence of macrovascular complications with respect to fasting or delta C-peptide quartiles. These results suggest that low C-peptide level is associated with diabetic microvascular, but not macrovascular complications in patients with type 2 diabetes mellitus.

Topics: Adult; Aged; Asian People; C-Peptide; Chronic Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Male; Microvessels; Middle Aged; Prevalence; Republic of Korea; Young Adult

C-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence of chronic complications in patients with type 2 diabetes.. Retrospective cohort study with a median follow-up of 14 years.. A representative cohort of 2113 patients with type 2 diabetes mellitus and a subgroup of 931 individuals from this cohort without chronic complications at baseline from a diabetic clinic were studied.. Patients with higher C-peptide levels had higher baseline BMI and triglyceride and lower HDL-cholesterol values. During the follow-up, 46.1% of the patients died. In a Cox proportional hazard model, after multiple adjustments, no significant association was found between the C-peptide tertiles and all-cause mortality or mortality due to cancer, diabetes or cardiovascular diseases. In the subgroup of 931 patients without chronic complications at baseline, the incidence of microvascular complications decreased from the first to the third C-peptide level tertile, while the incidence of cardiovascular disease did not differ. The risks for incident retinopathy (hazard ratio (HR)=0.33; 95% confidence interval (CI) 0.23-0.47), nephropathy (HR=0.27; 95% CI 0.18-0.38) and neuropathy (HR=0.39; 95% CI 0.25-0.61) were negatively associated with the highest C-peptide tertile, after adjusting for multiple confounders.. Higher baseline C-peptide levels were associated with a reduced risk of incident microvascular complications but imparted no survival benefit to patients with type 2 diabetes mellitus.

Topics: Aged; C-Peptide; Chronic Disease; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Italy; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors

Prevalence of metabolic syndrome (MetS) in type 2 diabetes and its association with vascular complications were studied in 637 Japanese type 2 diabetic patients. MetS was diagnosed using criteria proposed by the Japanese study group for the definition of MetS in 2005. The prevalence of MetS in patients studied was higher in males (45.9%) than females (28.0%). The prevalence of MetS was 53.0% in males and 35.4% in females in patients with duration of less than 10 years, and decreased with an increase in duration. Upon comparing patients groups complicated with and without MetS, we determined the MetS group had significantly higher levels of fasting serum C-peptide and high-sensitivity C-reactive protein, and a significantly lower level of serum adiponectin. However, the prevalence of coronary heart disease, brain infarction, or peripheral arterial disease was not significantly different between these groups. On the other hand, the prevalence of microangiopathy in the group with MetS was significantly higher than in that without MetS, and became significantly higher along with an increase in duration. This study clarifies the prevalence of MetS in Japanese type 2 diabetic patients, and suggests that MetS is associated with microangiopathy rather than macroangiopathy in Japanese type 2 diabetic patients.

Topics: Age of Onset; Aged; Body Mass Index; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Female; Humans; Japan; Male; Metabolic Syndrome; Middle Aged; Prevalence; Vascular Diseases

The relationship between C peptide and micro- and macrovascular complications is poorly known in type-2 diabetes mellitus. The aim of the study was to evaluatethe relationship between serum C-peptide level and chronic complications in patients with type-2 diabetes mellitus.. Three-hundred-eighteen patients (138 male, 180 female) with type-2 diabetes mellitus were included in the study. Microvascular (nephropathy, retinopathy and neuropathy) and macrovascular complications (coronary artery disease and peripheral vascular disease) were determined in all patients. In addition, presence of hypertension and smoking habit was recorded. Fasting serum glucose, lipid levels, HbA1c and C-peptide levels were measured in all patients.. There were 90 (28.3%) patients with sensorial neuropathy, 48 (15.1%) with autonomic neuropathy, 72 (22.7%) with nephropathy, 84 (26.4%) with retinopathy, 135 (42.5%) with hypertension, 270 (84.9%) with dyslipidemia, 33 (10.4%) with coronary artery disease and 18 (5.7%) with peripheral vascular disease. Serum C-peptide level was higher in patients with dyslipidemia (p = 0.045), hypertension (p = 0.001), coronary artery disease (p = 0.001), peripheral vascular disease (p = 0.001) and autonomic neuropathy (p = 0.001). Serum C-peptide level was not significantly different in patients with and without sensorial neuropathy, nephropathy and retinopathy. Serum C-peptide level was significantly associated with the presence of coronary artery disease (p = 0.001), peripheral vascular disease (p = 0.001) and autonomic neuropathy (p = 0.001). There was no relationship between C peptide and sensorial neuropathy, nephropathy and retinopathy.. Our findings indicate a relationship between C peptide and macrovascular but not microvascular compli cations in patients with type-2 diabetes mellitus.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Logistic Models; Male; Middle Aged; Risk Factors; Statistics, Nonparametric

The goal of this study was to examine the severity of exocrinous and endocrinous pancreatic incompetence, composition of bile acids (BA) and hemostasis state depending on the etiologic form of chronic pancreatitis (CP). The study comprised 76 patients with CP at the age of 33-74 (46 females and 30 males), 20 of them having alcoholic pancreatitis (AP), 26 --biliary pancreatitis (BP), and 30--involutional pancreatitis (IP); 15 people (without any signs of gastrointestinal tract lesions) made up the control group. CP was diagnosed based on clinical data, laboratory and instrumental assessments. Various degrees of severity of exocrinous and endocrinous pancreatic incompetence were revealed depending on the CP etiology. AP patients had more marked alterations of this type depending on the severity and presence of complications. The study revealed changes in the quantitative and qualitative BA composition, which can cause reduced absorption of exogenous cholesterol in the CP patients' bowels and be one of the reasons affecting the exocrinous function of the pancreas. IP patients had more marked alterations of this type. All CP patients had blood hypercoagulation accompanied by a reduction of the public constant of blood coagulation, increase of the coagulation index and clot elasticity. Patients with the complicated course of the disease had more marked alteration of this type.

Topics: Adult; Aged; Bile Acids and Salts; C-Peptide; Cholecystokinin; Chronic Disease; Feces; Female; Homeostasis; Humans; Male; Middle Aged; Pancreas; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis

Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.

Topics: Adult; Aged; Biomarkers, Tumor; C-Peptide; Case-Control Studies; Chronic Disease; Cohort Studies; Endometrial Neoplasms; Female; Humans; Hyperinsulinism; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Prognosis; Prospective Studies; Risk Factors

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

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

Latent autoimmune diabetes in adults (LADA) is subtype of diabetes type 1. It is well know, that 50% patients with new diagnosed diabetes type 2 present late complications. As far we don't know how many patients with new diagnosed diabetes have late complications according to presence of antibodies against islet antigens. The aim of the study was to compare late complications of diabetes: microangiopathy and macroangiopathy in newly diagnosed adult diabetic patients in relation to presence of humoral autoimmune markers.. We evaluated the presence of late complications in group of 41, hospitalized patients base on clinical examination and medical history. Glutaminic acid decarboxylase antibodies (anti-GAD), protein tyrosine phosphatase antibodies (anti-IA-2) and anti-insulin antibodies (IAA) titers were measured by RIA. The C peptide basal and stimulated, HbA1c, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, urea, creatinine levels and microalbuminuria were evaluated.. The presence of islet cell specific antibodies were shown in 25 subjects. We observed late complications in 13/25 (52%) in group with positive antibodies titers, and in 10/16 (62.5%) in group without antibodies. We diagnosed the nephropathy (16% vs 6.25%), retinopathy (12% vs 0%), polyneuropathy (20% vs 12.5%), hypertension (32% vs 50%), chronic heart disease (8% vs 25%), overweight (32% vs 50%) and hyperlipidemia (12% vs 25%) respectively in subjects with and without antibodies. The concentrations of total cholesterol (185 +/- 47.8 vs 218 +/- 38.7, p < 0.05) and creatinine level (0.8 +/- 0.15 vs 0.95 +/- 24, p < 0.05) were higher in group without antibodies, but fasting glycemia (181 +/- 69.1 vs 132 +/- 32.8, p < 0.05) was higher in the group presenting with autoantibodies. We did not observed the difference between level of glycosylated hemoglobin in the investigated groups.. There is the tendency to higher incidence of microangiopathy in group of patients positive to islet cell antibodies. Conversely the macroangiopathy appears frequently in patients without antibodies.

Topics: Adult; Autoantibodies; Biomarkers; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Female; Glutamate Decarboxylase; Humans; Insulin Antibodies; Islets of Langerhans; Male; Middle Aged; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases

There was a study of 19 chronic pancreatitis patients (10 male and 9 female), 11 chronic pancreatitis and pancreatogenic diabetes mellitus patients (8 male and 3 female) and 12 type 2 diabetes mellitus patients (4 male and 8 female) at the age of 30-60 as well as 15 control group subjects at the same age range. The content of the C-peptide and such peptides as INCINE, PAMG-cine and PAMG-tin in the blood serum was subjected to the immunoradiometric assay. It was discovered that there is a trend to the increased C-peptide level in CP patients while the C-peptide level in CP patients with diabetes mellitus was smaller than that in the control group; the C-peptide level in CP patients with type 2 diabetes mellitus was higher as compared to that in the control group. It was shown that erythrocytes of CP patients are less sensitive to insulin action and do not respond to the presence of insulinomimetic peptides under examination during the glucose uptake test. CP patients with diabetes mellitus and type 2 diabetes mellitus patients are more sensitive to the action of insulin and peptides applied. Synthetic insulinomimetic peptides can serve as a means for discovering the functional cell deficiency under the glucose uptake test.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Erythrocytes; Female; Glucose; Glycodelin; Glycoproteins; Humans; Insulin; Male; Middle Aged; Pancreas; Pancreatitis; Peptides; Pregnancy Proteins

This study examined the relationship of fasting serum glucose, insulin, C-peptide, glycosylated hemoglobin A (HbA1c), and Homeostasis Model Assessment (HOMA)-insulin resistance to risk of chronic kidney disease (CKD) among 6453 persons without diabetes (fasting glucose <126 mg/dl and not taking diabetes medication) who participated in the Third National Health and Nutrition Examination Survey and were aged 20 yr or older. CKD was defined as an estimated GFR <60 ml/min per 1.73 m(2). The prevalence of CKD was significantly and progressively higher with increasing levels of serum insulin, C-peptide, HbA1c, and HOMA-insulin resistance. After adjustment for potential confounding variables, the odds ratio of CKD for the highest compared with the lowest quartile was 4.03 (95% confidence interval [CI], 1.81 to 8.95; P = 0.001), 11.4 (95% CI, 4.07 to 32.1; P < 0.001), 2.67 (95% CI, 1.31 to 5.46; P = 0.002), and 2.65 (95% CI, 1.25 to 5.62; P = 0.008) for serum insulin, C-peptide, HbA1c levels, and HOMA-insulin resistance, respectively. For a one SD higher level of serum insulin (7.14 micro U/ml), C-peptide (0.45 Deltamol/ml), HbA1c (0.52%), and HOMA-insulin resistance (1.93), the odds ratio (95% CI) of CKD was 1.35 (1.16 to 1.57), 2.78 (2.25 to 3.42), 1.69 (1.28 to 2.23), and 1.30 (1.13 to 1.50), respectively. These findings combined with knowledge from previous studies suggest that the insulin resistance and concomitant hyperinsulinemia are presented in CKD patients without clinical diabetes. Further studies into the causality between insulin resistance and CKD are warranted.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Kidney Diseases; Male; Middle Aged; Nutrition Surveys; Risk Factors; United States

Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes.. Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements.. Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby.. Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.

Topics: Adult; Aged; C-Peptide; Cell Count; Chronic Disease; England; Female; Follow-Up Studies; Glycated Hemoglobin; Hospitals, General; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Organ Size; Pancreatectomy; Pancreatitis; Retrospective Studies; Time Factors; Transplantation, Autologous

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

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

To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical beta-cell damage and impaired insulin secretion, we screened 441 nondiabetic patients with autoimmune thyroiditis (AT) for GADab, and 15 (3.4%) were found positive. Antibodies to IA-2 were found in two GADab+ and one GADab- patients. We matched 11 GADab+ and 13 GADab- AT patients who were euthyroid on thyroxin supplementation, and 13 control subjects for sex, age, and body mass index and measured insulin, C-peptide, and glucagon response to glucose and arginine at three blood glucose concentrations (fasting, 14 mmol/liter, >25 mmol/liter). In the fasting state, all groups had similar blood glucose concentration and HbA1c level, but the serum insulin concentration was higher in the AT patients compared with the control subjects (P < 0.04). The acute insulin response to arginine was lower in GADab+ than in GADab- thyroiditis subjects at glucose concentration of 14 and >25 mmol/liter (AIR(14): 76.8 +/- 52.0 vs. 158.2 +/- 118.2 mU/liter, P = 0.040; AIR(>25): 84.3 +/- 64.4 vs. 167.9 +/- 101.5 mU/liter, P = 0.035). In conclusion, GADab were associated with a decreased insulin secretion capacity in nondiabetic subjects with thyroiditis, which suggests that GADab positivity could be a marker of subclinical insulitis.

Topics: Adult; Aged; Antibodies; Arginine; C-Peptide; Chronic Disease; Female; Follow-Up Studies; Glucagon; Glucose; Glutamate Decarboxylase; Humans; Injections, Intravenous; Insulin; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Thyroiditis, Autoimmune

Set point errors in glucose homeostasis that result in chronic, mild hyperglycemia in the setting of maturity onset diabetes of the young have been described. Similar set point errors may exist that result in chronic, asymptomatic glucopenia.. A healthy 39-year-old female was referred for evaluation of chronic, persistent, and asymptomatic glucopenia that persisted over the prior several years with a record of numerous random plasma glucose concentrations between 35 and 45 mg/dL. She denied ethanol intake and family history of hypoglycemia or diabetes. She was not taking any medications known to cause hypoglycemia, and a urine sulfonylurea screen was negative. Fasting insulin and C-peptide levels were not elevated, and pancreatic imaging studies were normal. We hypothesized that this patient possessed an error in glucose metabolism that resulted in chronic, asymptomatic glucopenia.. In a series of clinical studies, we demonstrated a nadir plasma glucose concentration of 35 mg/dL in the absence of symptoms during a 60-hour fast. C-peptide secretion was appropriately suppressed during symptomatic hypoglycemia with exogenous insulin infusion, and counterregulatory hormone secretion was intact during insulin-induced symptomatic hypoglycemia. Finally, the patient demonstrated an incremental increase in insulin concentration in response to minimal increases in plasma glucose during a sequential, stepped infusion of 10% dextrose.. We conclude that this patient exhibits features of a set point error in glucose homeostasis that manifests as chronic, asymptomatic glucopenia. Although the mechanism for this condition remains to be elucidated, such set point errors do exist and should be considered in the differential diagnosis of chronic hypoglycemia.

Topics: Adult; C-Peptide; Chronic Disease; Diagnosis, Differential; Female; Glucose; Homeostasis; Humans; Hypoglycemia

Topics: Acute Disease; Animals; C-Peptide; Chronic Disease; Diabetic Neuropathies; Disease Models, Animal; Insulin; Neural Conduction; Ranvier's Nodes; Rats; Sodium Channels

Up-regulation of urea synthesis by amino acids and dietary protein intake may be impaired in patients with chronic pancreatitis (CP) due to the reduced glucagon secretion. Conversely, urea synthesis may be increased as a result of the chronic inflammation. The aims of the study were to determine urea synthesis kinetics in CP patients in relation to glucagon secretion (study I) and during an increase in protein intake (study II).. In study I, urea synthesis rate, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine in 7 CP patients and 5 control subjects on spontaneous protein intake. The functional hepatic nitrogen clearance (FHNC), i.e. urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between urea synthesis rate and plasma alpha -amino nitrogen concentration. In study II, 6 of the patients of study I had urea synthesis and FHNC determined before and after a period of 14 days of supplementation with a protein-enriched liquid (dietary sequence randomized).. Study I: Alanine infusion increased urea synthesis rate by a factor of 10 in the control subjects, and by a factor of 5 in the CP patients (P<0.01). FHNC was 31.9+/-2.4 l/h in the control subjects and 16.5+/-2.0 l/h (P<0.05) in the CP patients. The glucagon response to alanine infusion (AUC) was reduced by 75 % in the CP patients. The reduction in FHNC paralleled the reduced glucagon response (r(2)=0.55, P<0.01). Study II: The spontaneous protein intake was 0.75+/-0.14 g/(kg x day) and increased during the high protein period to 1.77+/-0.12 g/(kg x day). This increased alanine stimulated urea synthesis by a factor of 1.3 (P<0.05), FHNC from 13.5+/-2.6 l/h to 19.4+/-3.1 l/h (P<0.01), and the glucagon response to alanine infusion (AUC) by a factor of 1.8 (P<0.05).. Urea synthesis rate and FHNC are markedly reduced in CP patients. This is associated with, and probably a result of, impaired glucagon secretion, and predicts a lower than normal postprandial hepatic loss of amino nitrogen. An increase in dietary protein intake increases alanine stimulated urea synthesis and FHNC by a mechanism that involves an increase in glucagon. This indicates that the low FHNC during spontaneous protein intake included an adaptation to the low protein intake, effectuated by a further decrease in glucagon secretion.

Topics: Adaptation, Physiological; Adult; Alanine; Blood Glucose; C-Peptide; Chronic Disease; Dietary Proteins; Female; Glucagon; Humans; Insulin; Liver Function Tests; Male; Middle Aged; Nitrogen; Pancreatitis; Urea

Topics: Adult; Blood Glucose; C-Peptide; Calcium Gluconate; Chronic Disease; Female; Glucose Clamp Technique; Humans; Hypoglycemia; Infusions, Intravenous; Insulin; Insulinoma; Pancreatic Neoplasms; Portal Vein

Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving "transient" insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the "gold standard" for monitoring islet autograft function, may require reappraisal.

Topics: C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Graft Survival; Humans; Insulin; Islets of Langerhans Transplantation; Pancreatectomy; Pancreatitis; Proinsulin; Transplantation, Autologous

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

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

Insulin-dependent diabetes mellitus (IDDM) is the second most prevalent chronic illness of children. Investigation of the treatment of IDDM is hindered by the lack of a reproducible and easily maintained non-human primate model of this disorder.. We induced IDDM in 11 juvenile cynomolgus monkeys after a single (150 mg/kg) intravenous injection of streptozotocin (STZ). All diabetic monkeys were treated with insulin twice daily, based on a sliding scale. Subcutaneous vascular access ports were surgically placed in each monkey to facilitate serial blood sampling and drug administration. Allogeneic pancreatic islet cells from unrelated donors were subsequently transplanted into the mesenteric circulation of all STZ-treated monkeys.. Mild, transient nausea and vomiting occurred in all animals after STZ injection; however, no additional signs of toxicity occurred. Within 36 hr, all monkeys required twice daily administration of exogenous insulin to maintain a non-ketotic state. Serum C-peptide levels decreased from >1.2 ng/ml before STZ, to between 0.0 and 0.9 ng/ml after STZ, confirming islet cell destruction. Animals were maintained in an insulin-dependent state for up to 147 days without any observable clinical complications. Subcutaneous vascular access port patency was maintained up to 136 days with a single incidence of local infection. Islet cell transplantation resulted in normoglycemia within 24 hr. Serum C-peptide levels increased (range: 2-8 ng/ml) for 6 - 8 days in immune competent animals, and for 39-98 days after transplant in immunosuppressed monkeys.. IDDM can be consistently induced and safely treated in juvenile cynomolgus monkeys. Chronic vascular access can be maintained with minimal supervision and complications. This model is appropriate for studies investigating potential treatments for IDDM including islet cell transplantation.

Topics: Animals; C-Peptide; Catheterization; Child, Preschool; Chronic Disease; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Femoral Vein; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Insulin; Insulin Infusion Systems; Islets of Langerhans Transplantation; Kidney; Macaca fascicularis; Pancreas; Streptozocin; Vascular Patency

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

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

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

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

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

The liver is the major source of circulating insulinlike growth factor-I (IGF-I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability. We aimed to assess the direct effects of liver dysfunction on serum levels of IGF-1 and its major binding proteins by measuring fasting levels of growth hormone, IGF-1, IGFBP-1, IGFBP-3, insulin, C peptide, and glucose in 35 patients with cirrhosis and during an oral glucose tolerance test in 16 of those patients. Serum levels of growth hormone (GH) were high in the patients: median, 12.0 mU/L (range, 1 to 87) compared with normals, 0.95 mU/L (0.1 to 20) (P < .0005) and serum IGF-1 levels were low: 81 ng/mL (38 to 153) versus 193 ng/mL (151 to 235) (P < .0001). Serum IGFBP-3 levels were low in the patients: 1.59 mg/L (0.46 to 4.43) compared with normals, 5.41 (4.34 to 6.11) (P < .0001), and there was a significant negative correlation between IGFBP-3 levels and Childs Pugh score (r = .63 P < .0001). Fasting IGFBP-1 levels were significantly higher in the patients 31 ng/mL (11 to 92) than normals, 14 (7 to 20) (P < .0001). There was no correlation between fasting insulin and IGFBP-1 levels despite high fasting insulin levels. A decrease in IGFBP-1 levels was seen during the glucose tolerance test (GTT) in all patients. In conclusion, there are significant changes in the levels of two of the major IGF-1 binding proteins that may further limit the bioavailability of already low circulating IGF-1 levels. Substrate availability appears to be a stronger influence on fasting IGFBP-1 levels than does insulin, and the close correlation of IGFBP-3 with liver function indicates a dominant regulatory role of the hepatocyte.

Topics: Adult; Blood Glucose; C-Peptide; Carrier Proteins; Chronic Disease; Fasting; Female; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Liver Diseases; Male; Middle Aged; Somatomedins

The exocrine and endocrine pathophysiology of chronic calcific pancreatitis of the tropics (CCPT) remains elusive. The objective of this study was to evaluate the spectrum and correlates of the exocrine and endocrine pancreatic dysfunction in CCPT. Thirty-seven consecutive patients with a clinico-radiological diagnosis of CCPT were stratified into three subgroups: CCPT-normal glucose tolerance (NGT), CCPT-abnormal glucose tolerance (IGT) and CCPT-diabetes mellitus (DM). Ten ketosis resistant young diabetic (KRDY) patients, 10 classical insulin dependent diabetes mellitus (IDDM) patients and 18 healthy matched controls were included for comparison. Fecal chymotrypsin (FCT) levels and blood C-peptide levels (basal and post i.v. glucagon stimulation) were estimated for assessing the exocrine and endocrine pancreatic functions, respectively. Sonography was performed to evaluate the pancreatic size and ductal diameter. Pancreatic exocrine-endocrine correlation was examined by studying the C-peptide/fecal chymotrypsin ratio (CP/FCT) (CP/FCT of normal controls = 1). Mean FCT levels in all 3 subgroups of CCPT (NGT: 3.4 micrograms/g; IGT: 0.82 microgram/g; DM: 2.4 micrograms/g) were very low (87-96% reduction in exocrine pancreatic dysfunction; mean FCT in healthy controls was 22.8 micrograms/g) (P < 0.0001). In contrast, KRDY and IDDM patients displayed 50-54% reduction in pancreatic acinar function (P < 0.001). Basal and stimulated C-peptide levels progressively fell in the 3 CCPT subsets (NGT: 0.23 and 0.46 > IGT: 0.14 and 0.29 > DM 0.10 and 0.14) (P < 0.01). CCPT patients exhibited pancreatic atrophy and ductal dilation (> 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Analysis of Variance; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Ultrasonography

The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Chronic Disease; Heart Failure; Humans; Insulin; Insulin Resistance; Male; Oxygen Consumption; Stroke Volume

Chronic pancreatitis (CP) leads to deterioration of the endocrine pancreatic function by fibrotic destruction. The aim of the present study was to investigate whether resection or duct drainage in patients with CP would have a direct impact on the pancreatic beta cell function. An intravenous glucose tolerance test (IVGTT) was performed before, after and in some cases 3 months after operation in ten patients each of whom had been treated by either resection or duct drainage. Three patients undergoing pancreatic resection for cancer served as controls. Beta cell function was assessed by glucose elimination (K-values), insulin and C-peptide response. K-Values in patients with CP were not significantly influenced after resection (1.93 +/- 0.78/2.13 +/- 0.72; n.s.) or drainage (1.26 +/- 0.47/1.54 +/- 0.58; n.s.) but reduced in all three tumor patients (2.23 +/- 0.55/1.23 +/- 0.43). The initial insulin response [microU/ml] in CP patients was also not altered after resection (19.7 +/- 17.3/16.0 +/- 18.2; n.s.) or after drainage (16.7 +/- 16.5/13.0 +/- 9.0; n.s.), whereas all three resected tumor patients showed reduced values (42.9 +/- 15.7/17.5 +/- 3.8). Stimulated C-peptide synthesis [ngmin/ml] was not substantially lowered in patients resected for CP (90.5 +/- 85.6/73.8 +/- 48.9; n.s.) or in the drainage group (121.3 +/- 67.5/98.0 +/- 57.2; n.s.), but this parameter was decreased in every tumor patient postoperatively (157.8 +/- 66.9/125.1 +/- 69.6). Resection in patients with chronic pancreatitis did not inevitably result in loss of beta cell function. Parenchyma-preserving drainage procedures had no measurable advantage in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; C-Peptide; Chronic Disease; Drainage; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatitis; Postoperative Complications

Topics: Adult; Alcoholism; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Female; Humans; Islets of Langerhans Transplantation; Liver Function Tests; Pancreatectomy; Pancreatitis; Time Factors; Tomography, X-Ray Computed; Transplantation, Autologous

In a prospective clinical-experimental study, 15 consecutive patients with chronic pancreatitis, operated on because of severe pain, were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th day postoperatively, and 3 months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, and pancreatic polypeptide were determined. As indicated by the k value, glucose tolerance improved postoperatively in 10 patients (66.6%); three patients (19.9%) showed no change, and one patient (6.6%) was worse. Only one patient (6.6%) developed evident diabetes mellitus immediately postoperatively. Pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (p < 0.01). The stimulation of pancreatic polypeptide after oral glucose was significantly lower postoperatively (p < 0.01). Duodenum-preserving pancreas head resection does not lead to an impairment of glucose tolerance in the majority of patients; a deterioration was observed only in few cases (13.3%).

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Kinetics; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; Prospective Studies

Immune recognition of the major structural proteins of rubella virus by peripheral blood mononuclear cells and synovial inflammatory infiltrates of a patient with documented chronic rubella associated arthritis was compared with responses of normal healthy rubella virus immunoreactive subjects to establish if there were unusual response patterns associated with rubella associated arthritis in this subject.. Synthetic peptides (16-33 amino acids in length) representing selected amino acid sequences of the rubella virus envelope (E1 and E2) and capsid (C) proteins were used in lymphocyte stimulation assays with peripheral blood mononuclear cells or synovial inflammatory infiltrates to determine T lymphocyte recognition of antigenic sites within the synthetic peptides. A rubella virus specific polymerase chain reaction was used to determine the persistence of rubella virus in the patient's cells.. The patient's peripheral blood mononuclear cells showed abnormally increased lymphoproliferative responses to three E1 synthetic peptides encompassing residues 219-234, 389-411, and 462-481, and one E2 synthetic peptide containing the sequence 50-72, of which the last three were predicted to contain T cell antigenic sites. Although the patient's peripheral blood mononuclear cells showed positive proliferative responses to C synthetic peptides, these were not unusual. The number of synthetic peptides within the E1, E2, and C panels recognised by the patient's peripheral blood mononuclear cells was greater than was previously observed in normal healthy subjects. The recognition of synthetic peptides by synovial inflammatory infiltrates was similar to peripheral blood mononuclear cells but the responses measured were lower. The polymerase chain reaction was negative for rubella virus detection in peripheral blood mononuclear cells and synovial inflammatory infiltrates.. Abnormally increased T cell recognition of antigenic sites within rubella virus E1 and E2 proteins observed in this patient with rubella associated arthritis suggests chronic antigenaemia due to persistent rubella virus in tissue sites other than peripheral blood mononuclear cells or synovial inflammatory infiltrates.

Topics: Aged; Arthritis; Arthritis, Infectious; C-Peptide; Chronic Disease; Female; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Polymerase Chain Reaction; Rubella virus; Synovial Fluid; Viral Envelope Proteins

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

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

Plasma lipase, C-peptide reactivity (CPR) and human pancreatic polypeptide (HPP) responses after ingestion of elemental diet were studied in 27 patients with chronic pancreatitis. These subjects were classified into 3 groups according to ERP findings; minimum or mild (MIP, n = 17), moderate (MOP, n = 6) and advanced (ADP, n = 4). Basal plasma lipase levels in the MIP and MOP patients were significantly higher than that in the controls (P < 0.05). Plasma CPR response (sigma delta CPR) in MIP cases were significantly higher than that in controls (P < 0.05). Also, plasma HPP (response (sigma delta HPP) in MIP cases were significantly higher than that in controls (P < 0.05). Plasma CPR and HPP responses correlated with the severity of chronic pancreatitis. Fourteen of the 17 MIP patients (82%) showed higher levels of basal lipase or sigma delta HPP in comparison to the respective normal ranges. This study suggested that the ED test may be more sensitive for detection of mild chronic pancreatitis and that it may be useful for evaluating exocrine and endocrine pancreatic functions in various stages of chronic pancreatitis.

Topics: C-Peptide; Chronic Disease; Female; Food, Formulated; Humans; Lipase; Male; Middle Aged; Pancreatic Function Tests; Pancreatic Polypeptide; Pancreatitis; Radioimmunoassay

Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Fluoresceins; Glucagon; Glucose; Humans; Insulin; Middle Aged; Pancreatitis; Radioimmunoassay; Thyrotropin-Releasing Hormone; Thyroxine

Chronic hyperinsulinemia in the fetal rhesus monkey results in fetal macrosomia without change in fetal plasma glucose concentration. After 18 days of hyperinsulinemia, fetuses were delivered by cesarean section, at which time experimental animals had significantly (P less than 0.05) elevated umbilical artery plasma insulin concentrations of 2039 +/- 854 pM compared with 129 +/- 72 pM. Plasma immunoreactive C peptide (IRCP) was significantly reduced to 39 +/- 17 pM compared with 286 +/- 134 pM. Eight hours after the insulin-delivering pumps were removed, plasma glucose, insulin, and IRCP were the same in both the experimental and control groups. At this time, 0.5 g glucose/kg was given intravenously and insulin and IRCP secretion was measured over a 1-hr period. The secretion, as assessed by integrating the incremental response of both insulin and IRCP, was significantly (P less than 0.05) lower by 80% in the experimental animals compared with the controls. Our data show that experimentally produced in utero euglycemic hyperinsulinemia in the fetal rhesus monkey produces a defect in the glucose-mediated insulin secretory mechanism that is detectable in the neonatal period even when hyperinsulinemia is no longer present. This study provides more support for the concept that fuel/hormone-mediated fetal teratogenesis may explain some of the fetopathy of the infant of the diabetic mother.

Topics: Animals; Animals, Newborn; Blood Glucose; C-Peptide; Chronic Disease; Female; Fetal Blood; Fetal Diseases; Glucose; Insulin; Insulin Secretion; Macaca mulatta; Pregnancy; Pregnancy in Diabetics

Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

Topics: Adult; Alcoholism; C-Peptide; Ceruletide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Pancreatitis; Secretin

In patients suffering from chronic pancreatitis with concomitant atrophic antral gastritis, gastrinemia is less whereas the response of pancreatic enzymic secretion to pentagastrin is more potent than in patients suffering from chronic pancreatitis without atrophic alterations in the gastroduodenal mucosa. The pancreas-stimulating effect of pentagastrin administered in a dose of 6 micrograms/kg is approximately equal to the action of 0.5 U/kg pancreozymine and noticeably yields to the effect of 1.5 U/kg pancreozymine (according to the criteria for output of intraduodenally secreted lipase and trypsin). The same diagnostic dose of pentagastrin used commonly for gastric secretion studies not only stimulates pancreatic enzyme secretion but also enhances the activity of beta-cells of Langerhans' islets of the pancreas in accordance with insulinemia and blood C-peptide determined by RIA.

Topics: C-Peptide; Cholecystokinin; Chronic Disease; Dose-Response Relationship, Drug; Gastrins; Gastritis, Atrophic; Humans; Insulin; Islets of Langerhans; Pancreas; Pancreatitis; Pentagastrin; Recurrence

We investigated the effect of chronic hyperglycemia on glucose transporters in erythrocytes of subjects with and without diabetes mellitus. We found a 22% increase in D-glucose-displaceable cytochalasin-B binding in erythrocyte membranes of diabetic subjects over those of controls (311 +/- 13 vs. 254 +/- 8 pmol/mg protein; P less than 0.001). This increased binding was due to a higher density of binding sites without a significant change in binding affinity. Cytochalasin-B binding to erythrocyte membrane correlated positively with both erythrocyte glycohemoglobin and serum glucose levels, but not with plasma C-peptide levels. The data are compatible with up-regulation of glucose transporters in the erythrocytes of subjects with chronic hyperglycemia. We suspect that this is brought about by increased synthesis and membrane incorporation of the glucose transporter during erythropoiesis.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Cytochalasin B; Diabetes Mellitus; Erythrocyte Membrane; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Middle Aged; Monosaccharide Transport Proteins; Reference Values

The mechanisms of carbohydrate metabolism abnormality were studied in 128 patients suffering from chronic pancreatitis by means of simultaneous measurement in the blood of glucose, insulin, C-peptide and glucagon concentrations both on an empty stomach and after the glucose tolerance test (50 g glucose). Five types of the hormonal mechanisms of hyperglycemia were revealed, caused by derangement of beta-cells for the most part, more rarely by alpha-cells of the pancreas and impairment of interregulation of those cells in chronic pancreatitis. The rate of the hormonal mechanisms of carbohydrate metabolism abnormality was shown to depend on the gravity and duration of chronic pancreatitis whereas blood sugar and insulin response to intravenous injection of glucose in patients with chronic pancreatitis to have characteristic features in common to type I and II diabetes.

Topics: Blood Glucose; C-Peptide; Carbohydrates; Chronic Disease; Glucagon; Humans; Insulin; Islets of Langerhans; Pancreatitis; Radioimmunoassay

Insulinemia, concentration of C-peptide and glucagon in the blood was studied in chronic hepatitis patients showing moderate tolerance disorders to glucose and diabetes mellitus developed against the background of chronic pancreatitis. Both groups showed hyperglucagonemia. Basal hypoinsulinemia and reduction of the C-peptide level revealed only in patients suffering of chronic pancreatitis with secondary diabetes mellitus. Reduced reaction of beta-cells of the pancreas to physiologic stimulation by pancreosozymin were observed also in less significant disorders of tolerance to glucose. The authors discuss the significance of changes in the sequential development of different degrees of disorders of the carbohydrate metabolism in patients with chronic recurrent pancreatitis.

Topics: C-Peptide; Carbohydrate Metabolism; Cholecystokinin; Chronic Disease; Diabetes Mellitus; Glucagon; Humans; Insulin; Islets of Langerhans; Pancreatitis; Recurrence

Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non-diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous-pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components.

Topics: Adult; Blood Glucose; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; India; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Trypsin

The content of gastrin, beta-endorphin, insulin, C-peptide in 129 patients with chronic gastric and duodenal diseases was studied by standard radioimmunoassay during the acute phase of the disease and after routine treatment. It is concluded that normalization of the hormonal homeostasis is one the criteria of treatment efficacy.

Topics: Adolescent; Adult; Aged; beta-Endorphin; C-Peptide; Chronic Disease; Duodenal Diseases; Female; Gastrins; Humans; Insulin; Male; Middle Aged; Peptides; Stomach Diseases

Variation in insulin and C peptide levels was examined in patients with angina of new onset and chronic coronary heart disease. Insulin secretion was increased in all coronary patients, as compared to the controls, and hormonal response to additional stress was abnormal in postmyocardial infarction patients. It is demonstrated that insulin secretion is already changed at early stages of coronary disease, and the pattern of change is presented.

Topics: Adult; Angina Pectoris; C-Peptide; Chronic Disease; Coronary Disease; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Physical Exertion; Rest

In 8 patients with diabetes mellitus type I two methods for intensified insulin treatment were compared: method of numerous insulin applications and treatment with a subcutaneous insulin pump (Microjet model of "Miles" company). The following were taken into consideration: daily insulin dose, residuary beta-cell secretion (determined by a venous Tolbutamide test and dynamic follow up of C-peptide), peripherial insulin efficiency (M) determined in vivo by an euglycemic hyperinsulinemic clamp-technique (Biostator). The infusion pump treatment imitates the beta-cell function better than the numerous insulin applications. This method of treatment helps in overcoming the insulin deficiency and the jatrogenic hyperinsulinemia and as a result the metabolic compensation and insulin efficiency are improved.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Drug Evaluation; Humans; Insulin; Insulin Infusion Systems; Tolbutamide

The patients with diabetes mellitus type I show a different course of the disease. In one group of patients diabetes runs a smooth and metabolic compensation is easily achieved and maintained. In another group of patients metabolic compensation is very difficult to achieve or it cannot be achieved at all. In 51 patients with diabetes mellitus type I the role of the residual beta-cell secretion and the insulin sensitivity for the stability of diabetes is studied. The endogenic insulin insufficiency, iatrogenic hyperinsulinemia and the related peripheral insulin resistance are the basic factors determining the stability of the insulin-dependent diabetes mellitus.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Chronic Disease; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Insulin Infusion Systems; Insulin Resistance; Islets of Langerhans; Male; Middle Aged; Tolbutamide

The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. This observation suggests that the recognition of glucose is more severely affected than that for non-glucose stimulants. To determine whether a similar selective decrease in glucose response was present before the onset of diabetes we studied two groups of non-diabetic identical twins of patients with recently diagnosed Type 1 diabetes: one group with complement-fixing islet cell antibodies who were at high risk of developing diabetes (four of the five have already developed diabetes) and a group without such antibodies at low risk of developing diabetes. In addition, a group of patients with chronic pancreatitis were studied to control for non-specific damage to the B-cell. Responses to i.v. glucose and i.v. glucagon were compared. Patients with chronic pancreatitis has similar responses to both glucose and glucagon and the responses did not differ from control subjects. The B-cells of the immune positive group showed evidence of pathology because the insulin and C-peptide responses to both stimuli were reduced when compared to either their control subjects or the immune negative twin group. However, the B-cell response to both glucose and glucagon in the immune positive twins was similar. Because the B-cell response to glucose was not less than that to glucagon, a selective destruction of the glucose recognition system cannot be a characteristic of all twins throughout the period before they develop Type 1 diabetes.

Topics: Adult; Autoantibodies; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis; Reference Values; Risk Factors; Twins, Monozygotic

In chronic pancreatitis with moderate derangements of carbohydrate tolerance (detected by the double glucose test), the basal concentrations of insulin and C-peptide in blood are normal whereas in patients with secondary diabetes mellitus are lowered. Glucagonemia is increased in patients of both groups. Euphylline (applied as an inhibitor of nucleotide phosphodiesterase), calcium gluconate and the adrenomimetic drug isadrin consistently increased insulinemia and the blood level of C-peptide in patients with chronic pancreatitis both with moderate and appreciable derangements of glucose tolerance. In patients with secondary diabetes that developed in the presence of pancreatitis, these drugs did not influence glucagonemia. The clinical prospects of the making use of the stimulating action of euphylline, calcium gluconate and isadrin on the function of beta-cells of the pancreas in chronic pancreatitis patients are under discussion.

Topics: Aminophylline; C-Peptide; Calcium Gluconate; Chronic Disease; Diabetes Mellitus; Glucagon; Gluconates; Glucose Tolerance Test; Humans; Insulin; Isoproterenol; Pancreas; Pancreatitis; Recurrence

The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsin, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages III-IV) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrine insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas.

Topics: Acute Disease; Antigens, Tumor-Associated, Carbohydrate; C-Peptide; Chronic Disease; Diagnosis, Differential; Fibrin Fibrinogen Degradation Products; Humans; Pancreatic Neoplasms; Pancreatitis; Recurrence; Trypsin

A study of 47 patients suffering of chronic pancreatitis indicates that the phase of exacerbation of the disease first showed changes in the parameters of external secretion while the incretory system of the pancreas, apparently, reveals disorders at a later phase. With the purpose of correction of the hormonal homeostasis it is recommended to use microcrystalline cellulose as an addition to the diet.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Combined Modality Therapy; Humans; Middle Aged; Pancreatitis; Trypsin

Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Food; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreatic Polypeptide; Pancreatitis; Somatostatin

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Antibodies; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Pancreatic Diseases; Prospective Studies; Uganda

The levels of immunoreactive insulin, C-peptide and insulin containing erythrocytes were studied in 26 patients on the 2nd and 12th day of their stay in hospital. A higher level of C-peptides was found in the patients as compared to healthy subjects. The level of immunoreactive insulin of the patients did not differ significantly from that of healthy subjects. The number of insulin containing erythrocytes in the patients was much lower than in healthy subjects. Their number after therapy did not rise considerably. There was no correlation between these indices.

Topics: C-Peptide; Chronic Disease; Erythrocytes; Humans; Insulin; Insulin Antibodies; Middle Aged; Pancreatitis; Recurrence

The aim of the present study was to evaluate insulin secretion by the pancreatic B cell in a group of patients with severe chronic pancreatitis and without overt diabetes. For this purpose we have measured plasma insulin and C-peptide peripheral levels in the fasting state and after a 100-g oral glucose load in 10 patients with severe chronic pancreatitis and fasting normoglycemia, and in 10 sex-, age-, and weight-matched healthy controls. As compared to normal subjects, patients with chronic pancreatitis showed: (1) significantly higher plasma glucose levels after oral glucose load (area under the plasma glucose curve 1708 +/- 142 vs 1208 +/- 47 mmol/liter X 240 min, P less than 0.005); (2) plasma insulin levels significantly higher at fasting (0.11 +/- 0.008 vs 0.08 +/- 0.005 nmol/liter, P less than 0.01) but not after oral glucose administration (area under the plasma insulin curve 79 +/- 12 vs 88 +/- 16 nmol/liter X 240 min); (3) significantly lower plasma C-peptide concentrations both in the fasting state (0.15 +/- 0.01 vs 0.54 +/- 0.05 nmol/liter, P less than 0.001) and after oral glucose load (area under the plasma C-peptide curve 211 +/- 30 vs 325 +/- 37 nmol/liter X 240 min, P less than 0.05). The finding of diminished plasma C-peptide levels suggests that chronic pancreatitis is associated with an impaired B-cell function even in the absence of overt diabetes. The increased or unchanged plasma insulin levels in spite of decreased plasma C-peptide concentrations indicate that in chronic pancreatitis insulin metabolism is reduced, most likely within the liver.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Fasting; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Pancreatitis; Time Factors

Nine patients with diabetes mellitus, type II (6 males and 3 females) were studied. The average duration of the disease was 7.1 years. The patients were perorally treated with glibenclamide (5-10 mg daily). Beta-cellular function was studied with glucagon as well as the peripheral insulin sensitivity of the patients on the background of the peroral treatment and after its two-week discontinuation--on the background of dietetic treatment. No significant difference in beta-cellular function, insulin sensitivity and metabolic compensation was established. Part of the patients with diabetes mellitus, type II, treated with low and medium doses of glibenclamide, could well be compensated only by an adequate diet.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Female; Glucagon; Glyburide; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Sulfonylurea Compounds

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreatitis

Topics: Adult; C-Peptide; Chronic Disease; Fasting; Food; Glucagon; Humans; Insulin; Middle Aged; Pancreas; Pancreatitis; Trypsin

A possible immunogenetic basis for diabetes in chronic pancreatitis was explored by studying 19 patients with both disorders, most of whom required treatment with insulin. In contrast to patients with insulin-dependent (Type 1) diabetes, patients with diabetes and chronic pancreatitis had residual beta cell function but blunted C-peptide responses to intravenous glucagon, absence of circulating islet cell antibodies, and HLA-DR types similar to control subjects and patients with chronic pancreatitis without diabetes. Diabetes complicating chronic pancreatitis is therefore not associated with the biochemical or immunogenetic markers characteristic of Type 1 diabetes.

Topics: Adult; Aged; Autoantibodies; Blood Glucose; C-Peptide; Chronic Disease; Cytoplasm; Diabetes Mellitus, Type 1; Female; HLA-DR Antigens; Humans; Islets of Langerhans; Male; Middle Aged; Pancreatitis

An intravenous glucose tolerance test was carried out to compare chronic pancreatitis patients (n = 17) who had undergone partial duodenopancreatectomy with (n = 9) and without (n = 8) occlusion of the residual pancreatic duct by Prolamin. The results obtained in 10 healthy volunteers were plotted as background information reflecting the normal metabolic response. Insulin- and C-peptide secretion were greatly decreased after both resection alone, and resection plus occlusion. However, the glucose tolerance (integrated glucose; K-values) appeared relatively well preserved in the two groups. The decrease in insulin appeared more marked after resection plus occlusion as compared with the non-occluded group. It is concluded that partial duodenopancreatectomy without or with ductal occlusion impairs insulin secretion, and leaves tolerance to an intravenous glucose load relatively stable. The mechanism underlying the latter observation is unknown at present.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Methods; Middle Aged; Pancreatitis; Postoperative Complications

Radioimmunoassay was employed to study blood content of insulin, C-peptide and glucagon in 78 patients with chronic pancreatitis. It was revealed that during exacerbation, there was an increase in the content of insulin and glucagon and, to a lesser degree, in that of C-peptide. During remissions, part of the patients showed insular deficiency which increased with disease standing. When pancreatitis lasted from 1 to 5 years or from 5 to 10 years, diabetes mellitus was recorded in 9.4% of the patients and in 16% of the patients, respectively.

Topics: C-Peptide; Chronic Disease; Glucagon; Humans; Insulin Antibodies; Pancreatic Hormones; Pancreatitis; Radioimmunoassay; Recurrence

In 11 persons with normal pancreas function and 21 patients with chronic pancreatitis serum levels of insulin and C-peptide were measured under basal conditions and after maximal stimulation with glucose-tolbutamide-glucagon. Patients with the highest excretory deficiency in the secretin-pancreozymin test had the most marked impairment in endocrine function. In patients with manifest diabetes the exocrine capacity was reduced to an average of 10% of normal. The endocrine parameters correlated linearly with the exocrine ones, most markedly C-peptide reserve with pancreatic enzyme secretion.

Topics: Adult; C-Peptide; Chronic Disease; Chymotrypsin; Diabetes Mellitus; Female; Humans; Insulin; Male; Pancreas; Pancreatitis; Trypsin

The degree of correlation between exocrine pancreatic function and endocrine secretory capacity was examined in 13 chronic pancreatitis patients with secondary diabetes mellitus, 8 chronic pancreatitis patients without diabetes, and 11 healthy subjects. The two parameters were studied under maximal stimulation (volume-corrected secretin-pancreozym test and glucose-tolbutamide-glucagon provocation, respectively). A close, linear correlation was found between all endocrine variables and pancreatic acinar function (e.g. rs = 0.77 for chymotrypsin output and C-peptide release; p less than 0.0001). The correlation was less strong with pancreatic bicarbonate output (e.g. rs = 0.49 for C-peptide release; p less than 0.05). In our patients, secondary overt diabetes occurred in chronic pancreatitis when protease outputs were, on an average, reduced to about 10% of the mean maximal protease output of normal subjects.

Topics: Adult; C-Peptide; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatic Function Tests; Pancreatic Hormones; Pancreatitis

Endocrine function of the pancreas was examined in patients with chronic pancreatitis of different etiology. Radioimmunoassay was applied to measure blood immunoreactive insulin, C-peptide and glucagon as characteristics of the hormonal activity of the pancreas. Pancreatic function was revealed to be disordered. The degree of the disorders correlated with the disease gravity and duration as well as with its progress (exacerbation or remission). As compared with patients presenting with cholepancreatitis, more remarkable alterations, which were particularly well observable during making the glucose tolerance test, were found in patients with chronic pancreatitis of alcoholic etiology.

Topics: Alcoholism; Blood Glucose; C-Peptide; Chronic Disease; Fatty Liver; Female; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis; Proinsulin

Topics: Adult; C-Peptide; Chronic Disease; Fatty Acids, Nonesterified; Female; Glucagon; Growth Hormone; Humans; Insulin; Insulin Antagonists; Insulin Resistance; Liver Diseases; Male; Middle Aged

Carbohydrate and lipid metabolism were studied in 10 patients who had undergone total pancreatectomy. The results were compared with Type I diabetic patients and normal subjects, all of whom were matched for age, sex and weight. At the same level of glycemic control, the daily need for insulin was significantly lower in the patients with pancreatogenic diabetes than in those with Type I diabetes. Concentrations of serum total VLDL and HDL triglyceride were higher in the pancreatectomized patients than in the diabetic or normal controls, whereas concentrations of serum total and LDL cholesterol were significantly lower. The composition of the VLDL, LDL and HDL particles was abnormal in the totally pancreatectomized patients as all three lipoprotein fractions were enriched in triglyceride. HDL2 cholesterol was similar in the totally pancreatectomized patients to that in the other two groups but HDL3 cholesterol was lower. Postheparin plasma lipoprotein lipase and hepatic lipase activities were normal. It is concluded that in totally pancreatectomized patients the changes in the lipoprotein profile on reflect more the action of various confounding factors, i.e. malabsorption, continuance of alcohol abuse and dietary changes than the impact of the diabetes itself.

Topics: Adult; Blood Glucose; C-Peptide; Carbohydrates; Chronic Disease; Diabetes Mellitus, Type 1; Heparin; Humans; Lipids; Lipoprotein Lipase; Lipoproteins; Liver; Middle Aged; Pancreatectomy; Pancreatitis

Insulin and C-peptide in venous blood were determined during oral glucose tolerance testing in 59 non-manifest diabetics with histologically established chronic liver disease (fatty degeneration, chronic aggressive hepatitis, cirrhosis). Glucose tolerance was pathologic in 60-80% of patients. When compared to a control group patients with chronic liver disease showed significantly increased values of blood glucose (after glucose intake), of insulin and of C-peptide (fasting and after glucose intake). The C-peptide/insulin ratio, a measure of hepatic insulin degradation, was significantly decreased after glucose uptake. There were no significant differences of blood sugar, insulin and C-peptide among the various liver diseases. In chronic aggressive hepatitis and in cirrhosis the C-peptide/insulin ratio was partly significantly lower than in fatty degeneration. From the increased C-peptide values increased insulin secretion in chronic liver diseases can be deducted. In addition, the decreased C-peptide/insulin ratios show an impairment of insulin degradation in liver cirrhosis and other chronic hepatic diseases. However, in fatty liver degeneration this is clearly less pronounced than in more serious liver diseases.

Topics: C-Peptide; Chronic Disease; Fatty Liver; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Insulin; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

Plasma concentrations of pancreatic glucagon, C-peptide, and pancreatic polypeptide were measured during arginine stimulation in 16 patients with chronic pancreatitis, in eight subjects with idiopathic diabetes mellitus, and in seven healthy controls. The hormone responses were compared with exocrine pancreatic function as assessed using the urinary excretion rate of p-aminobenzoic acid after oral ingestion of n-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). The increase in pancreatic glucagon levels during arginine stimulation was significantly reduced in patients with chronic pancreatitis compared to healthy controls, most markedly in those with secondary diabetes. In contrast, the glucagon response was unimpaired in patients with idiopathic diabetes. The arginine-induced increase in plasma glucagon and C-peptide concentrations correlated significantly with urinary PABA excretion in chronic pancreatitis (P less than 0.001, P less than 0.01, respectively). The responses of plasma C-peptide and pancreatic polypeptide separated pancreatitic and idiopathic diabetes less well. Thus, the glucagon response to arginine distinguished secondary diabetes due to chronic pancreatitis and idiopathic diabetes mellitus. The correlation between urinary PABA excretion and glucagon levels suggests that in chronic pancreatitis there is a parallel impairment of exocrine and endocrine function.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Arginine; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; para-Aminobenzoates

Topics: Blood Glucose; C-Peptide; Chronic Disease; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Insulin Secretion

Optimum multimodality examination of the pancreas includes sonographic, radioimmunological, scintigraphic and angiographic studies. Sonography is a method of choice to study anatomotopographic features of the pancreas. The radioimmunoassay is intended both for the mass screening of patients with hepatogastro-duodenal diseases and for the differential diagnosis of chronic pancreatitis by the nature and type of disease. The use of pancreatoscintigraphy should be restricted in view of considerable exposure of patients. Angiography and angioscanning should be performed strictly according to indications with suspicion for a pancreatic tumor.

Topics: Antigens, Neoplasm; C-Peptide; Chronic Disease; Diagnosis, Differential; Humans; Insulin; Pancreas; Pancreatic Diseases; Pancreatic Function Tests; Pancreatic Neoplasms; Pancreatitis; Radiography; Radioimmunoassay; Radionuclide Imaging; Trypsin; Ultrasonography

In order to investigate whether a relationship exists between in vivo insulin secretion and islet mass, 8 patients suffering from severe chronic relapsing pancreatitis were studied before and after pancreatectomy by glucose-glucagon-test (per os 1.75 g glucose; i.v. glucagon 0.01 mg/kg b.w.) and by intravenous glucose-tolerance-test (iGTT) (i.v. glucose 0.33 g/kg b.w.). Postoperative in vitro assessments of pancreatic insulin and alpha-amylase content were performed, and morphometric studies were carried out. Patients were characterized by reduced c-peptide secretion when compared with healthy subjects. The c-peptide response to the glucose-glucagon-test correlated well with the morphometrically estimated exocrine and islet tissue mass (P less than 0.05) and with the content of insulin and amylase in the tissue. The findings suggest that in subjects suffering from severe chronic relapsing pancreatitis the maximal insulin response might represent a parameter for the patient's islet mass.

Topics: Adult; Blood Glucose; C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatitis

The effect of mild hypercalcaemia on the growth hormone (GH), C-peptide and glucose responses to arginine infusion in patients with insulin-dependent idiopathic diabetes mellitus (ID) was compared with that observed in patients whose diabetes was secondary to idiopathic haemochromatosis (IH) and chronic pancreatitis (CP). The summated GH responses to arginine infusion alone were similar in all three groups. Mild hypercalcaemia significantly diminished the GH response to arginine in patients with secondary diabetes, but not in those with ID. As the blood glucose and C-peptide responses were similar in the presence of a normal or raised serum calcium, the differences in GH response could not be ascribed to changes in blood glucose levels or to alterations in endogenous insulin release. For reasons as yet unknown, hypercalcaemia appears to have more of a stabilizing effect on the pituitary somatotrophic granules of those with secondary diabetes than in those with ID.

Topics: Adult; Arginine; C-Peptide; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Female; Growth Hormone; Hemochromatosis; Humans; Hypercalcemia; Male; Middle Aged; Pancreatitis

Insular apparatus function in primary chronic and reactive pancreatitis associated with hepatobiliary pathology was studied in 178 patients by radioimmunoassay. The authors showed typical changes of insulin and C-peptide concentration in the presence of an i.v. glucose tolerance test that make it possible to differentiate in combination with the trypsin concentration in the serum primary and reactive pancreatitis as well as exacerbation and remission stages of the disease.

Topics: C-Peptide; Chronic Disease; Glucose Tolerance Test; Humans; Insulin; Pancreas; Pancreatic Function Tests; Pancreatitis; Radioimmunoassay; Trypsin

In five totally pancreatectomized human subjects the secretion of gut-derived glucagons was stimulated by ingestion of a meal rich in fat and carbohydrates. Glucagon-like immunoreactivity in plasma, measured with an antiserum against the 6-15 sequence, increased fivefold in response to the meal. Glucagon like immunoreactivity measured with a antiserum against the C-terminal sequence was initially normal (12-13 pmol/l), increased slightly (to 20 pmol/l), and then decreased (to approximately 6 pmol/l). The chromatographic profile of glucagon-like immunoreactivity in plasma at maximum stimulation was studied after concentration by affinity chromatography. Both assay systems identified two peaks (at Kd-values of 0.30 and 0.60-0.65, and 0.30 and 0.70, respectively). The position at Kd 0.70 corresponds to that of glucagon 1-29. The same components may be identified in plasma from normal subjects. It is concluded that the human intestine is capable of generating all of the molecular forms of glucagon which normally are present in plasma.

Topics: Adult; Aged; C-Peptide; Chronic Disease; Dietary Carbohydrates; Dietary Fats; Glucagon; Humans; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis

Exocrine pancreatic function was evaluated by a Lundh meal test and a secretin-cholecystokinin test in 16 patients with chronic pancreatitis. B cell function was assessed by measuring the concentration of C-peptide after stimulation with oral glucose and intravenous glucagon. The Cc-peptide response to intravenous glucagon and oral glucose was closely correlated (r = 0.88, p less than 0.01). Plasma C-peptide after glucagon was significantly correlated to the post-prandial concentration of lipase (r = 0.72, p less than 0.001), amylase (r = 0.64, p less than 0.05) and to amylase output (r = 0.64, p less than 0.05). Eight out of nine patients treated with insulin had residual B cell function, but it diminished significantly with increasing duration of diabetes. We conclude that B cell function is correlated to pancreatic enzyme secretion and that patients with insulin-treated diabetes secondary to chronic pancreatitis have a residual insulin secretion similar to that of patients with Type 1 (insulin-dependent) diabetes.

Topics: Adult; Aged; Amylases; Bicarbonates; C-Peptide; Chronic Disease; Female; Glucagon; Glucose Tolerance Test; Humans; Islets of Langerhans; Lipase; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Pancreatitis

Topics: C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Liver Diseases; Peptides

Topics: Biliary Tract Diseases; C-Peptide; Chronic Disease; Diagnosis, Differential; Humans; Pancreatitis; Peptides; Radionuclide Imaging; Trypsin

In 64 patients suffering from chronic inflammatory liver disease (alcoholic hepatitis, chronic active hepatitis, chronic persistent hepatitis) significantly increased values of blood glucose and insulin, free fatty acids and C-peptide were observed during a 100 g oral glucose load. Fasting values of blood glucose, free fatty acids and C-peptide were also increased, while serum growth hormone remained unchanged. In patients with chronic active hepatitis the C-peptide/insulin-ratio, a measure for hepatic insulin degradation, was significantly lowered after glucose uptake. During oral load there were no discernible differences between the different types of chronic inflammatory liver disease concerning blood glucose, serum insulin and free fatty acids. In normal weight and in overweight patients suffering from liver disease blood glucose and serum insulin values were increased to the same extent. As it is known from the liver cirrhosis chronic inflammatory liver disease lead to an insulin resistance, to which elevated free fatty acid levels contribute. Increased body weight has no influence on the insulin resistance observed in chronic liver inflammation. From the changes of the C-peptide and the C-peptide/insulin-ratio it can be deduced, that the hyperinsulinism in patients with chronic inflammatory liver disease is due to both insulin hypersecretion and diminished hepatic insulin degradation.

Topics: Adult; Blood Glucose; Body Weight; C-Peptide; Chronic Disease; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Hepatitis; Humans; Hyperinsulinism; Male; Middle Aged

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.

Topics: Adult; C-Peptide; Chronic Disease; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatitis; Transplantation, Autologous; Transplantation, Homologous

Pancreatic-type glucagon (PTG) has been found in the plasma of totally pancreatectomized human beings. Arginine infusion, however, caused no increase in PTG. Pancreas-resected patients had a normal response of PTG to arginine and a subnormal increase in C peptide. Gut glucagon-like immunoreactants (gut GLI) were increased in resected patients and further increased in totally pancreatectomized patients. Gut GLI showed no change during arginine stimulation.

Topics: Adult; Aged; Arginine; C-Peptide; Chronic Disease; Female; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Pancreas; Pancreatectomy; Pancreatitis; Peptides; Radioimmunoassay

Late results were obtained from the follow up of 48 patients with chronic pancreatitis, who underwent partial duodenopancreatectomy. We measured the rest function of the remaining B-cells after resection by daily glucose profile, i.v.-gtt, measurements of the glucagon stimulated C-peptide-output and the amount of C-peptide in the 24-h-urine. In 9% of the cases the operation induced diabetes in addition to the already existing 31%. 3/4 of the nondiabetics showed a latent diabetic metabolism (K value < 1.0). The cause of this, as shown by the C-peptide-analysis, was the loss of the endocrine functional reserve following pancreas resection because of chronic pancreatitis. Therapeutically great differences resulted in reaching and equilibrium of serum glucose in the pancreas resected insulin-dependent patients, because they were dependent on carbohydrates for energy. The tendency to hypoglycaemia represented an additional endangerment.

Topics: Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus; Duodenum; Follow-Up Studies; Humans; Islets of Langerhans; Pancreatectomy; Pancreatitis; Postoperative Complications

Topics: Adult; Aged; C-Peptide; Chronic Disease; Female; Humans; Male; Middle Aged; Pancreatitis; Peptides

A 36-year-old man suffering from chronic pancreatitis involving the whole organ had total duodenopancreatectomy. The Langerhans' islets were isolated from the extirpated organ and transplanted into the liver via portal artery. Insulin substitution could be lowered from 50 I.U. to 12 I.U. by the 5th post operative day. Repeatedly, raised insulin levels could be verified in response to high blood sugar loads. C-peptide and glucagon were also found. 7 months after transplantation the islets still seem to be functioning.

Topics: Adult; C-Peptide; Chronic Disease; Duodenum; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans Transplantation; Liver; Male; Pancreatectomy; Pancreatitis; Transplantation, Autologous

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.

Topics: Adolescent; Adult; Antigens; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Humans; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Obesity; Peptides

Topics: C-Peptide; Chronic Disease; Humans; Insulin; Liver Diseases; Pancreatitis; Peptides; Radioimmunoassay

To clarify the mechanism of hyperinsulinism of hepatic cirrhosis, plasma insulin and C-peptide levels before and after oral glucose loads were measured in 34 patients with cirrhosis, 15 patients with chronic hepatitis, and 25 normal subjects. While plasma immunoreactive insulin (IRI) levels during oral glucose tolerance testing (OGTT) were significantly increased in cirrhotics, plasma immunoreactive C-peptide (CPR) levels were elevated slightly. The C-peptide to insulin ratio throughout OGTT was significantly smaller in cirrhotics than in normal subjects (P less than 0.01). A decreased hepatic insulin degradation rate has been suggested to one of the main causes of hyperinsulinism in hepatic cirrhosis. The ratio of the difference between basal and 30-min CPR values and basal and 30-min OGTT blood glucose values [delta CPR: delta BS(30)'] as well as the delta IRI: delta BS(30') ratio was significantly decreased in cirrhotics (P less than 0.01). These results indicate that insulin secretion in response to a glycemic stimulus is reduced in cirrhotics. Both the ratios of the sums of six IRS and CPR values of OGTT (sigma CPR: sigma IRI) and delta CPR: delta BS(30') and sigma CPR: sigma BS(30') were found in inverse relationship with indocyanine green retention rate in cirrhotics.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Chronic Disease; Female; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Kinetics; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged

Topics: Adult; Blood Glucose; C-Peptide; Chronic Disease; Female; Glucagon; Humans; Kidney; Kidney Diseases; Kinetics; Male; Middle Aged; Pancreatic Hormones