Increased insulin sensitivity and decreased insulin secretion in offspringof insulin-sensitive type 2 diabetic patients

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous gluc ose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offs pring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offs pring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 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 a nd the controls. The rate of glucose disappearance (KG) was significantly l ower 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 x 10(-4).min(-1).pmol/L. P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the con trol group (886 +/- 110 v 2,296 +/- 267 min pmol/L, P < .01). Glucose effec tiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versu s the controls (2.106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, bath n ormal glucose tolerance (NGT) offspring and IGT offspring showed a signific ant decrease in FPI and increase in Si. Thus, although the offspring of ins ulin-sensitive type 2 diabetics had increased insulin sensitivity, the impa irment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an ins ulin secretory dysfunction despite increased insulin sensitivity. Copyright (C) 2000 by W.B. Saunders Company.