Insulin secretion and insulin sensitivity defects are a common feature of mild, clinically homogeneous, recently diagnosed type II (Non-insulin-dependent) diabetics

Alteration in insulin secretion and reduced peripheral sensitivity to the hormone have been reported in type II diabetes. In this paper, a comparison is made of basal glucose production (³H-6 glucose), insulin secretion and insulin sensitivity in vivo (hyperglycemic clamp) and in vitro (binding to circulating monocytes) in 24 patients with recently diagnosed type II diabetes, matched for age and fasting glycemia and divided into non-obese (14 subjects) and moderately obese (10 subjects), and in 9 non-obese controls. The non-obese diabetics were slightly hyperinsulinemic during fasting (10.8±1.0 vs 4.8±0.8 μU/ml in controls, p < 0.0005), with a significant reduction in early and late insulin secretion (14.0±1.5 vs 20.8 ± 2.0 μU/ml, p<0.01 and 24.8±3.3 vs 34.7±2.14 μU/ml, p<0.025). The insulin sensitivity index MCR/I was significantly reduced (2.30±0.32 vs 4.14±0.40, p<0.005). Endogenous glucose production was significantly increased (107±10.2 vs 84±3.7 mg/m² per min, p<0.025) and displayed a positive correlation with fasting glycemia (r=0.51, p<0.05). Insulin binding to monocytes was significantly lower than in controls (2.36±0.22%vs 4.06±0.32%, p<0.0005). Moderately obese diabetics also were significantly hyperinsulinemic in the fasting state (18.1±2.8 μU/ml, p<0.0005 vs controls) but, typically, lacked the early secretory phase (20.6±3.6 μU/ml vs baseline, n.s.). A similar increase of hepatic glucose production (107±11.2 mg/m² per min, p<0.025 vs controls, n.s. vs non-obese diabetics) and decrease of peripheral sensitivity to insulin (MCR/I=1.78±0.31, p<0.0005 vs controls, n.s. vs non-obese diabetics) was found in moderately obsese diabetics, as well as a significant reduction of insulin binding to insolated monocytes (2.62±0.4% p<0.01 vs controls, n.s. vs non-obese diabetics). These results confirm that common defects of both non-obese and moderately obese type II diabetics are: lack of early phase of glucose induced insulin secretion, increase in hepatic glucose production and decrease of peripheral insulin sensitivity together with reduction of insulin binding to circulating monocytes. The hypothesis of a unique defect as a cause of hyperglycemia in type II diabetes in early clinical phase is not borne out by the results of this study. Moderate obesity, even if able to reduce insulin sensitivity, seems to be less important in determining hyperglycemia.