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

Abstract

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/m 2; fasting plasma glucose, 4.54 ± 0.37 mmol/L), was assigned in random order to four groups (I, II, III, 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.