c-peptide and Atrophy

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

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

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

The effect of exocrine pancreatic function on the glucose-mediated insulin response and glucose utilization were studied in an exocrine pancreas-insufficient (EPI) pig model. Five 10-week-old EPI pigs after pancreatic duct ligation and 6 age-matched, non-operated control pigs were used in the study. Blood glucose, plasma insulin and C-peptide concentrations were monitored during meal (MGTT), oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Upon post-mortem examination, the pancreatic remnants of the EPI pigs showed acinar fibrotic atrophy but normal islets and β-cell morphology. The EPI pigs displayed increased fasting glucose concentrations compared with control animals (6.4 ± 0.4 versus 4.8 ± 0.1 mmol l(-1) , P < 0.0001) but unchanged insulin concentrations (2.4 ± 0.6 versus 2.1 ± 0.2 pmol l(-1) ). During the OGTT and IVGTT, the EPI pigs showed slower, impaired glucose utilization, with the disruption of a well-timed insulin response. Plasma C-peptide concentrations confirmed the delayed insulin response during the IVGTT in EPI pigs. Oral pancreatic enzyme supplementation (PES) of EPI pigs improved glucose clearance during IVGTT [AUC(glucose) 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P < 0.0001] without reinforcing the release of insulin [AUC(C-peptide) 14.4 ± 3.8 nmol l(-1) × (120 min) in EPI versus 6.4 ± 1.3 nmol l(-1) × (120 min) in EPI + PES, P < 0.002]. The results suggest the existence of an acino-insular axis regulatory communication. The presence of pancreatic enzymes in the gut facilitates glucose utilization in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme-dependent mechanism involved in peripheral glucose utilization.

Topics: Animals; Atrophy; Blood Glucose; C-Peptide; Eating; Fibrosis; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Ligation; Pancreas, Exocrine; Pancreatic Ducts; Sus scrofa; Swine; Weight Gain

Pancreatic atrophy is common in longstanding type 1 diabetes, but there are limited data concerning pancreas size at diagnosis.. Our objective was to determine whether pancreatic size was reduced in patients with recently diagnosed type 1 diabetes and assess whether pancreatic volume was related to residual β-cell function or islet autoantibodies.. We conducted a controlled cohort study with strict inclusion criteria, recruiting from hospital diabetes clinics between 2007 and 2010. PATIENTS AND HEALTHY CONTROLS: Participants included 20 male adult patients (median age 27 yr) with recent-onset type 1 diabetes (median duration 3.8 months) and 24 male healthy controls (median age 27 yr).. Interventions included noninvasive magnetic resonance imaging, collection of fasting blood samples, and glucagon stimulation testing in patients.. We compared pancreatic volume estimates between patients with recent-onset type 1 diabetes and healthy controls as planned a priori.. Scans were analyzed by an experienced radiologist blinded to diabetes status. Pancreatic volume correlated with body weight in patients and controls (P = 0.007). After adjustment for body weight, mean pancreatic volume index was 26% less in patients (1.19 ml/kg, se 0.07 ml/kg) than in controls (1.61 ml/kg, se 0.08 ml/kg) (P = 0.001). No correlation was seen between pancreatic volume index in patients and diabetes duration, glucose or C-peptide levels, glycated hemoglobin, and islet autoantibodies.. Pancreatic volume is reduced by 26% in patients with type 1 diabetes within months of diagnosis, suggesting that atrophy begins years before the onset of clinical disease. Pancreatic atrophy within individuals is therefore a potential clinical marker of disease progression.

Topics: Adolescent; Adult; Atrophy; Blood Glucose; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 1; Disease Progression; Humans; Insulin; Magnetic Resonance Imaging; Male; Organ Size; Pancreas

Exocrine function has been described in patients with diabetes. We hypothetized that patients with exocrine dysfunction have pancreatic atrophy.. This is a cohort study of hospitalized patients. Thirty-five patients were selected after detection of impaired exocrine function in routine tests, and 17 patients were matched for age and body mass index to the previous cohort. The pancreatic volume was evaluated on sections of computed tomographic scans of the pancreas. Other investigations included a glucagon stimulation test and determination of fecal elastase-1 concentration and chymotrypsin activity.. Fifty-two patients participated in this study, 24 with type 1 diabetes and 28 with type 2 diabetes. Duration of diabetes was 15 years (5-26 years; median [interquartile range]). The pancreatic volume, 42 cm (25-57 cm), was decreased in most patients. It did not differ in patients with type 1 diabetes compared with those with type 2 diabetes. It was decreased in patients treated with insulin and in those with low elastase-1 concentration or low chymotrypsin activity. In the multiple linear regression analysis, the pancreatic volume correlated with chymotrypsin activity and stimulated C-peptide.. We have unraveled a link between 2 old observations in patients with diabetes: atrophy of the pancreas and exocrine deficiency. These observations give credence to the reality of the exocrine dysfunction in patients with diabetes.

Topics: Adult; Aged; Atrophy; C-Peptide; Chymotrypsin; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Feces; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Organ Size; Pancreas; Pancreas, Exocrine; Pancreatic Elastase; Tomography, X-Ray Computed

We report the immunological and pathological findings of a 52-year-old woman, who died two years after the second of two islet transplants performed using the Edmonton protocol. After each islet transplant, she gradually lost insulin independence while maintaining low levels of C-peptide secretion.. A complete autopsy was performed including pathological and immunohistochemical analysis of hepatic allogeneic islets and native pancreatic islets to identify rejection or autoimmunity. Elispots assays for allogeneic sensitization and autoantibody assays for autoimmunity were performed antemortem after her islet transplantations to test in vitro for evidence of allogeneic sensitization or autoimmunity.. The cause of death was a hypertensive stroke. Small numbers of islets without inflammation were identified within portal venules and stained with insulin. The atrophic pancreas contained small numbers of islets, which stained for insulin, and lacked any inflammation within or adjacent to the islets. In vitro assays for alloantibodies were negative, and Elispots assays failed to identify allogeneic sensitization. In vitro assays for diabetic associated autoantibodies did not identify autoimmune resensitization. The allografted kidney showed only early changes of recurrent diabetic nephropathy, and no evidence of rejection.. In summary, no evidence was found to support an immunological basis (either allo or autoimmunity) for the slow loss of intrahepatic islets, which may, therefore, be related to nonimmunological anatomic and physiological abnormalities of islets infused into the portal veins or to drug toxicity.

Topics: Atrophy; Autopsy; C-Peptide; Diabetes Mellitus, Type 1; Fatal Outcome; Female; Glycated Hemoglobin; Graft Rejection; Graft Survival; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Middle Aged; Portal Vein; Treatment Failure

Pancreas tissue collected from 77 patients died of Keshan disease as well as pancreas specimens of experimental rats having been fed with grains collected from Keshan disease endemic area were studied with immunohistochemical stainings. There were lesions found morphologically in the pancreatic islets of the patients, including atrophy, reduction of number, abnormal arrangement and degeneration of the islet cells. The serum insulin and connective peptide levels as well as the connective peptide secretory reserve in the islets of rats fed with endemic area grains were all markedly decreased. These findings suggest that the islet lesions in Keshan disease may be an important factor in aggravating the development of necrosis in the myocardium.

Topics: Adolescent; Animals; Atrophy; C-Peptide; Cardiomyopathies; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Infant; Insulin; Islets of Langerhans; Male; Pancreas; Rats; Rats, Wistar; Selenium; Sodium Selenite; Vitamin E

Insulin has a trophic effect on pancreatic acinar tissue, so the pancreas might be expected to atrophy in persons who have diabetes. Accordingly, we analyzed the density, contour (smooth or lobulated), and thickness of the pancreas on CT scans of diabetic patients and compared the results with those in control subjects. The prevalence of pancreatic lobulation (incisurae deeper than 2 mm) and its correlation with age in diabetic and control subjects were determined. The thickness of the pancreas was measured at three levels (head, body, tail). Three groups of diabetic patients were examined: 20 insulin-dependent patients, 25 patients not treated with nor dependent on insulin, and 12 patients treated with but not dependent on insulin. A control group included 57 nondiabetic patients. The ages of the control subjects were similar to those of the diabetic patients. The statistical significance of the differences between groups of diabetic patients and control subjects was estimated by using Student's t test for the values of density and thickness and the chi 2-test for the prevalence of pancreatic lobulation. The density of the pancreas in diabetic patients and control subjects was not statistically different. Diabetic patients had increased lobulation of the pancreas. All parts of the pancreas tended to be smaller in diabetic patients, but the degree of reduction varied. It was modest in the patients not treated with insulin, pronounced in insulin-dependent patients, and intermediate in non-insulin-dependent, insulin-treated patients. Moreover, the size of the body was significantly reduced in all three groups, whereas the size of the pancreatic head was preserved in patients not treated with insulin. In conclusion, CT of the pancreas shows that although density in diabetic patients is normal, lobulation is increased. Reduction in size involves the body of the pancreas more than other parts of the gland and is more pronounced in insulin-treated diabetic patients. CT of the pancreas might be useful to predict which diabetic patients will require insulin therapy.

Topics: Adult; Aged; Aged, 80 and over; Aging; Atrophy; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Diseases; Reference Values; Tomography, X-Ray Computed

Topics: Amylases; Atrophy; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Pancreas; Pancreas Transplantation; Postoperative Complications