Insulin sensitivity is impaired in adults with varying degrees of GH deficiency

Abstract

Severe GH deficiency (GHD) is arbitrarily defined by a peak GH (pGH) response to provocative tests of less than 3 microg/l. The impact of lesser degrees of GHD (pGH of 3-7 microg/l) in the adult is less well defined. Hypopituitary adults with severe GHD are insulin resistant as defined by the short insulin tolerance test (ITT), homeostatic model assessment (HOMA) or the hyperinsulinaemic euglycaemic clamp. Whether insulin action is impaired in the presence of lesser degrees of GHD (GH insufficiency, GHI) is not known. We studied 30 patients with GHD (median pGH 0.5 microg/l; 0.3-1.3 microg/l), 24 with GHI (median pGH 4.0 microg/l; 3.6-4.9 microg/l), and 30 age-, sex- and body mass index (BMI)-matched controls. A short ITT was performed in a subset of 20 patients from each group and the rate constant for glucose disappearance (K(ITT)) calculated. Both GHD and GHI hypopituitary adults were found to be insulin resistant from the K(ITT) values compared with the control group [analysis of variance (anova) on ranks, -0.0210 vs. -0.0223 vs. -0.0261, P < 0.05]. No difference in K(ITT) values was detected between the GHD and GHI groups. Calculation of insulin resistance using the HOMA did not detect a significant difference between groups (anova on ranks, 2.04 vs. 1.54 vs. 1.34, P = 0.40). No significant difference in the fasting glucose, insulin or IGFBP-I levels between groups was detected. Insulin resistance estimated from the K(ITT) correlated with the serum IGF-I (r = -0.30, P = 0.01), and pGH level to the ITT (r = -0.31, P = 0.03). K(ITT) also correlated with total body percentage fat mass (r = -0.28, P = 0.03). Multivariate analysis found K(ITT) to be dependent on percentage fat mass, gender and age (r = 0.53, P = 0.0002). Insulin resistance increased in concert with percentage fat mass, age and male gender. Although not detected under basal conditions, hypopituitary adults with both severe GHD and GHI are insulin resistant under conditions of insulin stimulation. This finding may be explained by the concomitant adverse changes in body composition observed in both these states of varying degrees of GHD. Insulin resistance is associated with a number of adverse cardiovascular risk factors that may place patients with GHI at risk of premature cardiovascular disease.