Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation: A sign of impaired  -cell function?

Abstract

OBJECTIVE -In response to hyperglycemia, ␤-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all ␤-cell hormones. RESEARCH DESIGN AND METHODS-Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, ␤-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 Ϯ 1 kg/m 2 , 47 Ϯ 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 Ϯ 1 kg/m 2 , 50 Ϯ 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 Ϯ 1 kg/m 2 , 47 Ϯ 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT).RESULTS -PKT patients had higher fasting amylin (19 Ϯ 3 vs. control subjects: 7 Ϯ 1 pmol/l) and insulin (20 Ϯ 2 vs. control subjects: 10 Ϯ 1 U/ml; each P Ͻ 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P Ͻ 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9 -31% higher (P Ͻ 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P Ͻ 0.05). OGIS was not significantly different between groups. ␤-Cell sensitivity to glucose was reduced in PKT patients (Ϫ64%, P Ͻ 0.009). Fasting plasma amylin was inversely associated with ␤-cell sensitivity to glucose (r ϭ Ϫ0.543, P Ͻ 0.004).CONCLUSIONS -After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired ␤-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired ␤-cell function in type 1 diabetic patients after PKT.

Effects of Gastric Bypass Surgery on Insulin Resistance and Insulin Secretion in Nondiabetic Obese Patients

“…Hepatic insulin resistance index was calculated by multiplying fasting insulin concentrations with fasting EGP as described by Gastaldelli et al (18) and in analogue by multiplying fasting C-peptide concentration with EGP. Hepatic insulin extraction articles Bariatric surgery (HIE) (as percentage of the secreted hormone) was approximated by a function of (1-(AUC insulin /AUC C-peptide )) as previously described (19). HOMA was calculated as a measure for basal insulin sensitivity (20).…”

Fasting and postprandial liver glycogen content in patients with type 1 diabetes mellitus after successful pancreas–kidney transplantation with systemic venous insulin delivery

“…Liver glucose metabolism in pancreas-kidneytransplanted patients T1DM-PKT patients with systemic venous drainage represent a coherent human model that allows studying the effects of systemic insulin release on liver glucose metabolism without the impact of hyperglycaemia: Successful kidney pancreas transplantation leads to normoglycaemia without necessity of any glucose-lowering drugs, 6,12,13 because these patients get adequate insulin supply from their pancreas transplant in the manner of a "closed-loop-system". Previous studies reported minor defects in non-oxidative glucose metabolism in T1DM-PKT patients: One study in insulin-resistant pancreas-transplant recipients investigated muscle glucose metabolism by obtaining skeletal muscle biopsies during insulin infusion and detected a reduced capacity to store muscle glycogen.…”

“…4,5 In patients with T1DM with terminal kidney disease, successful combined pancreas and kidney transplantation (PKT) results in normalization of glycaemic control. 6 However, in T1DM-PKT with systemic venous drainage of the pancreas, pancreatic hormones are released directly into the systemic circulation. In Correspondence: Christian-Heinz Anderwald, Associate Professor of Internal Medicine, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.…”

Adipokines in type 1 diabetes after successful pancreas transplantation: normal visfatin and retinol‐binding‐protein‐4, but increased total adiponectin fasting concentrations

“…Successful PKTx results in sustained normoglycaemia without the necessity of exogenous insulin supply and protects the body from progression of long-term diabetic complications and the effects of glucolipotoxicity. 14,15 We hypothesized that in T1DM after PKTx long-term normoglycaemic metabolism combined with restored endogenous insulin and C-peptide secretion could at least in part reverse some of the alterations of adipokines seen in T1DM.…”