Functional β-Cell Mass and Insulin Sensitivity Is Decreased in Insulin-Independent Pancreas-Kidney Recipients

Abstract

To compare functional beta-cell mass and insulin sensitivity in insulin-independent pancreas-kidney recipients with that in age- and body mass index-matched nondiabetic kidney recipients and normal controls. All transplant recipients were on maintenance immunosuppression with mycophenolate mofetil and tacrolimus since more than 2.7 years (2.2-3.8 years). Their C-peptide release was measured during a 170-min hyperglycemic clamp, first in absence and then in presence of glucagon. Data were compared with those after glucose stimulation alone. Insulin sensitivity under basal and stimulated conditions was calculated using homeostasis model assessment of insulin resistance and insulin sensitivity index, respectively. Functional beta-cell mass in pancreas-kidney recipients with systemic venous drainage was reduced, representing, respectively, 63% and 80% of that in healthy controls and kidney recipients. Pancreas-kidney recipients exhibited lower insulin sensitivity than healthy controls (homeostasis model assessment of insulin resistance was 0.8, 0.7-1.1 vs. 0.4, 0.3-0.8; P=0.02 and insulin sensitivity index was 17, 12-24 mg/kg/min per 100 microU/mL vs. 31, 20-38 mg/kg/min per 100 microU/mL; P=0.04). Using a hyperglycemic clamp, the functional beta-cell mass in insulin-independent pancreas-kidney recipients was found to be 37% and 20% lower than in healthy controls and nondiabetic kidney recipients.