Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation

Abstract

OBJECTIVE—In response to hyperglycemia, β-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 β-cell hormones. RESEARCH DESIGN AND METHODS—Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, β-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 ± 1 kg/m2, 47 ± 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 ± 1 kg/m2, 50 ± 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 ± 1 kg/m2, 47 ± 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 ± 3 vs. control subjects: 7 ± 1 pmol/l) and insulin (20 ± 2 vs. control subjects: 10 ± 1 μU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9–31% higher (P < 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 < 0.05). OGIS was not significantly different between groups. β-Cell sensitivity to glucose was reduced in PKT patients (−64%, P < 0.009). Fasting plasma amylin was inversely associated with β-cell sensitivity to glucose (r = −0.543, P < 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 β-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired β-cell function in type 1 diabetic patients after PKT.