Minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in Type 1 (insulin-dependent) diabetic pancreas allograft recipients

Abstract

Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two-and eight-fold greater in Group 1 (36±6 μU/ml) than in Group 2 (17±7 μU/ml) and Group 3 (4.5±0.6 μU/ml), respectively. Following intravenous glucose (t=0 min) and tolbutamide (t=20), peak incremental insulin levels were significantly (p<0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89±0.45) and Group 2 (4.11±1.30), respectively, when compared to GroupS (8.40±1.24×10-1 min-1 (μU/ml)-1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48±0.26; Group 2, 2.05±0.21; and Group 3, 2.10±0.17×10-2·min-1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients. © 1992 Springer-Verlag.