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 familiar 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.