Insulin Sensitivity and β-Cell Function in Adults with Lifetime, Untreated Isolated Growth Hormone Deficiency

Context: GH reduces insulin sensitivity (IS), whereas IGF-I increases it. IGF-I seems to be critical for the development of the beta-cells, and impaired IS has been reported in GH deficiency (GHD). Objective: The aim of the study was to assess IS and beta-cell function in adult patients with untreated isolated GHD (IGHD) due to a homozygous mutation in the GHRH receptor gene. Design, Setting, and Patients: We conducted a cross-sectional study in 24 GH-naive adult IGHD subjects and 25 controls. Intervention: We performed an oral glucose tolerance test with glucose and insulin measurements at 0, 30, 60, 90, 120, and 180 min. Main Outcome Measures: IS was assessed by homeostasis model assessment index of insulin resistance (IR), quantitative IS check index, oral glucose IS in 2 h (OGIS2) and 3 h (OGIS3). beta-Cell function was assayed by homeostasis model assessment index-beta, insulinogenic index, and area under the curve of insulin-glucose ratio. Results: During the oral glucose tolerance test, glucose levels were higher in IGHD subjects (P < 0.0001), whereas insulin response presented a trend toward reduction (P = 0.08). The number of individuals with impaired glucose tolerance was higher in the IGHD group (P = 0.001), whereas the frequency of diabetes was similar in the two groups. Homeostasis model assessment index of IR was lower (P = 0.04), and quantitative IS check index and OGIS2 showed a nonsignificant trend toward elevation (P = 0.066 and P = 0.09, respectively) in IGHD. OGIS3 showed no difference between the groups. Homeostasis model assessment index-beta, insulinogenic index, and ratio of the areas of the insulin and glucose curves were reduced in the IGDH group (P = 0.015, P < 0.0001, and P = 0.02, respectively). Conclusions: Adult subjects with lifetime congenital untreated IGHD present reduced beta-cell function, no evidence of IR, and higher frequency of impaired glucose tolerance. (J Clin Endocrinol Metab 97: 1013-1019, 2012)