Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/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 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/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 approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of the FPIR measured during IVGTT is not significantly affected by the duration of the glucose infusion. However, the magnitude of the difference in FPIR observed between the two protocols highlights the need for standardization of the methodology if the IVGTT is to be used in studies of the preclinical stage of IDDM.