Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

Abstract To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] v 4.6 ± 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 ± 2.5 v 28.3 ± 2.5 pmol/L, P ± = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (K G ) was significantly lower in the offspring versus the control group (2.00 ± 0.22 v 2.60 ± 0.17 min −1 , P = .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 ± 0.41 v 1.71 ± 0.17 × 10 −4 · min −1 · pmol/L, P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 ± 110 v 2,296 ± 267 min · pmol/L, P G ) was comparable between the offspring and control groups. The disposition index (Si × FPI) was significantly lower in the offspring versus the controls (2,106 ± 256 v 3,652 ± 490 × 10 −4 , P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.