INSULIN-RESISTANCE IN GROWTH HORMONE-DEFICIENT ADULTS - DEFECTS IN GLUCOSE-UTILIZATION AND GLYCOGEN-SYNTHASE ACTIVITY

Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, a nd body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (similar to 55 mU/L) clamp in conjunction with paired muscle biopsies for meas urement of glycogen synthase fractional velocity (FV0.1). Despite simi lar basal rates of total glucose disposal (Rd), there was a 64% reduct ion in the insulin-stimulated rise (Delta) in Rd in the GHD adults com pared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mu mol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (Delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mu mol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexe s of Rd(0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS(0.25 +/- 0.0 7 vs. 0.72 +/- 0.13 mu mol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by similar to 50% in GHD a dults (P = 0.07 us. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite sim ilar basal FV0.1. Using multiple and stepwise regression analysis, dur ation of GH deficiency, fasting triglycerides and fasting insulin acco unted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly d ue to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficien cy, fasting triglycerides, and fasting insulin.