Hyperinsulinemia in offspring of non-insulin-dependent diabetes mellitus patients: the role played by abnormal clearance of insulin

Insulin resistance and hyperinsulinemia are often found in first-degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients, and are currently considered a familial trait of this population at increased risk for diabetes. This study was undertaken to determine the role played by the metabolic clearance rate (MCR) of insulin (MCR.I) in the hyperinsulinism of these subjects. The proband population, consisting of 48 subjects aged 29.2 -+ 4.4 (mean _+SD} years (18 men and 30 women; body mass index, 24.6 -+ 0.8 kg / m2; fasting plasma glucose, 4.54 -+ 0.37 mmol / L), was assigned in random order to four groups (I, II, Ill, and IV), each receiving a double insulin/glucose infusion (I, 0.025/2.0; II, 0.050/3.5; III, 0.100/6.0; and IV, 0.200/8.0 U/kg • h and mg/kg • min, respectively) to calculate MCR-I and MCR of glucose (MCR-G). Forty (14 men and 26 women) age- and body mass index-matched healthy individuals served as controls. All subjects had a normal response to an oral glucose tolerance test (75 g) according to World Health Organization criteria. Basal plasma insulin and C-peptide levels in probands were significantly (P < .05) higher than in controls in each study group; similarly, MCR-I was significantly (at least P < .05) lower in probands than in controls in all groups. MCR-G was significantly (at least P < .05) decreased in probands as compared with controls of groups III and IV. These results suggest that a reduced plasma insulin removal by body tissues is operative in the offspring of NIDDM patients, and explain, at least in part, the hyperinsulinemia/insulin resistance in the early phase of the natural history of diabetes mellitus.