Insulin sensitivity, glucose effectiveness, and insulin secretion in nondiabetic offspring of patients with non-insulin-dependent diabetes mellitus:: A cross-sectional study

To evaluate the factors that determine the worsening of intravenous glucose tolerance in subjects at high risk for developing non-insulin-dependent diabetes mellitus (NIDDM), 15 glucose-tolerant offspring of NIDDM patients and 21 control subjects were studied. Each subject underwent a frequently sampled intravenous glucose tolerance (FSIGT) test. The intravenous glucose tolerance index (KG index) was calculated between minutes 10 and 40 of a FSIGT test. Insulin sensitivity (S-I), glucose effectiveness at zero insulin (GEZI), and first- and second-phase insulin responsiveness (Phi(1) and Phi(2)) were estimated using glucose and insulin kinetic minimal models. The acute insulin response to glucose (AIRg) was calculated as the area under the insulin curve above the basal level between 0 and 10 minutes, and the suprabasal insulin effect was determined by the product of S-I times AIRg. Offspring had a lower S-I than control subjects (14.1 +/- 7.5 v 9.25 +/- 4.20 x 10(-5) . min(-1)(pmol . L-1)(-1), P < .01), and their AIRg was similar (3,284 +/- 2,280 v 3,105 +/- 1,499 pmol . L-1, NS). Sample division according to the median K-G value showed that control subjects with low tolerance had a lower AIRS (4,417 +/- 2.531 v 2,043 +/- 1.068 pmol . L-1, P < .05) and a lower suprabasal insulin effect (0.057 +/- 0.03 v 0.023 +/- 0.009 min(-1), P < .05) than control subjects with high tolerance. Offspring with low tolerance had a lower AIRg (2,574 +/- 1,197 v 3,707 +/- 1.656 pmol . L-1, P < .05) and a lower GEZI (0.101 +/- 0.05 v 0.212 +/- 0.08 . 10(-1) . min(-1), P < .05) than offspring with high tolerance. Offspring with high and low tolerance showed lower Phi(1) (375 +/- 155 v 272 +/- 181 v 698 +/- 336 (pmol . L-1)min(mmol . L-1), NS) than control subjects with high tolerance. In conclusion, our data suggest that decreases in GEZI and AIRS are the main factors responsible for the worsening of intravenous glucose tolerance in the offspring of NIDDM patients. Copyright (C) 1999 by W.B. Saunders Company.