INCREASED GLUCOSE EFFECTIVENESS IN NORMOGLYCEMIC BUT INSULIN-RESISTANT RELATIVES OF PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS -A NOVEL COMPENSATORY MECHANISM

20 normoglycemic first degree relatives of non-insulin-dependent diabe tes mellitus (NIDDM) patients were compared with 20 matched subjects w ithout any family history of diabetes using the intravenous glucose to lerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60+/-0.14 vs 1.59+/-0.18, x 10(-2) min(-1), NS). Ho wever, insulin sensitivity (Si) was reduced (1.49+/-0.43 vs 4.80+/-0.6 1, x 10(-4) min(-1) per mU/liter, P = 0.05), whereas glucose effective ness (Sg) was increased (1.93+/-0.14 vs 1.52+/-0.16, x 10(-2) min(-1), P < 0.05) in the relatives. Despite insulin resistance neither fastin g plasma insulin concentration (7.63+/-0.48 vs 6.88+/-0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56+/-0.53 vs 4.13 +/-0.62, mU/liter min(-1) per mg/dl, NS) were increased in the relativ es. Phi1 was reduced for the degree of insulin resistance in the relat ives so that the Phi1 x Si index was lower in the relatives (11.5+/-2. 2 vs 16.7+/-2.0, x 10(-4) min(-2) per mg/dl, P < 0.05). Importantly, g lucose effectiveness correlated with Kg and with basal glucose oxidati on but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resis tance in first degree relatives of NIDDM patients. However, insulin se cretion was altered and reduced for the degree of insulin resistance i n the relatives, whereas glucose effectiveness was increased. We hypot hesize that increased glucose effectiveness maintains glucose toleranc e within normal limits in these ''normoinsulinemic'' relatives of NIDD M patients.