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 di abetes mellitus (NIDDM), 15 glucose-tolerant offspring of NIDDM patients an d 21 control subjects were studied. Each subject underwent a frequently sam pled intravenous glucose tolerance (FSIGT) test. The intravenous glucose to lerance index (KG index) was calculated between minutes 10 and 40 of a FSIG T test. Insulin sensitivity (S-I), glucose effectiveness at zero insulin (G EZI), and first- and second-phase insulin responsiveness (Phi(1) and Phi(2) ) were estimated using glucose and insulin kinetic minimal models. The acut e insulin response to glucose (AIRg) was calculated as the area under the i nsulin curve above the basal level between 0 and 10 minutes, and the suprab asal insulin effect was determined by the product of S-I times AIRg. Offspr ing had a lower S-I than control subjects (14.1 +/- 7.5 v 9.25 +/- 4.20 x 1 0(-5) . min(-1)(pmol . L-1)(-1), P < .01), and their AIRg was similar (3,28 4 +/- 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 l ower 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 toler ance had a lower AIRg (2,574 +/- 1,197 v 3,707 +/- 1.656 pmol . L-1, P < .0 5) 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 tole rance 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 conc lusion, our data suggest that decreases in GEZI and AIRS are the main facto rs responsible for the worsening of intravenous glucose tolerance in the of fspring of NIDDM patients. Copyright (C) 1999 by W.B. Saunders Company.