Insulin secretion in growth hormone-deficient adults: Effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone

beta-Cell function in growth hormone (GH)-deficient (GHD) adults is poorly documented. beta-Cell function was therefore studied in 10 GHD adults (age, 40 +/- 3 years; weight, 79.3 +/- 4.8 kg; body mass index [BMI], 27.5 +/- 1 .3 kg . m(-2)) before and after 6- and 24-month recombinant human GH (rhGH) therapy (0.24 IU . kg(-1) . wk(-1)) compared with 10 age-, sex-, weight-, and BMI-matched control subjects. With rhGH therapy, fat-free mass (FFM) in creased (48.2 +/- 4.9, 52.5 +/- 4.8, and 59 +/- 6.8 kg, respectively) and f at mass (FM) decreased (33.8% +/- 2.8%, 28.0% +/- 3.0%, end 29.4% +/- 2.5%, respectively), as did serum cholesterol. Oral glucose tolerance initially deteriorated at 6 months, but improved toward the control value by 24 month s. Fasting insulin (FI) increased significantly, as did the acute insulin r esponse to oral glucose (Delta AIR(OGTT)/Delta G) at 30 minutes (FI: pretre atment 9.8 +/- 0.8, 6 months, 14.0 +/- 1.8, 24 months 12.5 +/- 1.6 v contro l 11.4 +/- 1.9 mU . L-1; Delta AIR(OGTT)/Delta G: pretreatment 201 +/- 24, 6 months 356 +/- 41, 24 months 382 +/- 86 v control 280 +/- 47 mU . mmol(-1 )). However, the acute insulin response to intravenous (IV) glucose (AIR(G) ) and IV glucagon at euglycemia and hyperglycemia did not change with rhGH therapy and were similar to the control group values. Importantly, the expe cted reciprocal relationships (as observed for the control group) between t he various insulin secretory parameters and insulin sensitivity (SI) either were not present or were statistically weak in GHD subjects, despite the 3 5% decrease in SI by 24 months of rhGH therapy. In particular, over time, t here was an attenuation of insulin secretion with respect to the ongoing in sulin resistance with rhGH therapy, particularly for AIRG at 24 months. Aft er 5 days of rhGH withdrawal, insulin secretion decreased and SI improved i n GHD subjects. It is concluded that the current long-term rhGH treatment r egimens appear to impact on insulin secretion such that the normal relation ships between insulin secretion and SI are altered despite the favorable im pact on body composition and serum lipid profiles. Copyright (C) 1999 by W. B. Saunders Company.