Decreased Glucose Effectiveness but Not Insulin Resistance in Glucose-tolerant Offspring of Japanese Non-insulin-dependent Diabetic Patients: a Minimal-model Analysis

The aim of the study was to estimate insulin sensitivity (SI), insulin secretion, and glucose effectiveness (SG) in 10 subjects with normal glucose tolerance (eight men and two women) with a family history of non-insulin-dependent diabetes mellitus (NIDDM offspring). Ten glucose-tolerant subjects (eight men and two women) without a family history of NIDDM served as control subjects. All subjects were Japanese. They underwent a modified frequently sampled intravenous glucose tolerance test (FSIGT): glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg over 5 minutes) was infused from 20 to 25 minutes after glucose. SI and SG were estimated by Bergman's minimal-model method. No significant difference was observed in body mass index (22.6 +/- 1.5 v 21.5 +/- 0.6 kg/m2) and fasting glucose (5.1 +/- 0.1 v 5.2 +/- 0.1 mol/L) and insulin (40.7 +/- 6.3 v 42.6 +/- 6.7 pmol/L). SI was not different between the two groups (0.83 +/- 0.11 v 0.94 +/- 0.15 x 10(-1).min-1.pmol/ L-1, P > .05). The acute insulin response to glucose (AIRglucose) estimated by intravenous glucose tolerance testing was significantly lower in the offspring than in the normal controls (2,139 +/- 265 v 3,438 +/- 318 pmol/L.min, P < .05). The glucose disappearance rate (KG) and SG were significantly diminished in the offspring versus normal controls (KG, 1.50 +/- 0.22 v 2.10 +/- 0.15 min-1, P < .05; SG, 0.016 +/- 0.003 v 0.023 +/- 0.002 min-1, P < .05). Thus, glucose-tolerant Japanese NIDDM offspring with normal insulin sensitivity are characterized by a reduced AIRglucose and diminished SG. This is the first report that glucose resistance but not insulin resistance already exists in glucose-tolerant Japanese NIDDM offspring.