The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation

GH has been proposed as a therapy for patients with HIV-associated fat accu mulation, but the pharmacological doses (6 mg/d) used have been associated with impaired fasting glucose and hyperglycemia. In contrast, physiologic d oses of GH (similar to 1 mg/d) in HIV-negative men reduced visceral adiposi ty and eventually improved insulin sensitivity, despite initially causing i nsulin resistance. We conducted an open-label study to evaluate the effects of a lower pharmacologic dose of GH (3 mg/d) in eight men with HIV-associa ted fat accumulation. Oral glucose tolerance, insulin sensitivity, and body composition were measured at baseline, and I and 6 months. Six patients co mpleted I month and 5, 6 months of GH therapy. IGF-I levels increased 4-fol d within I month of GH treatment. Over 6 months, GH reduced buffalo hump si ze and excess visceral adipose tissue. Total body fat decreased (17.9 +/- 1 0.9 to 13.5 +/- 8.4 kg, P = 0.05), primarily in the trunk region. Lean body mass increased (62.9 +/- 6.4 to 68.3 +/- 9.1 kg, P = 0.03). Insulin-mediat ed glucose disposal, measured by a euglycemic hyperinsulinemic clamp, decli ned at month 1 (49.7 +/- 27.5 to 25.6 +/- 6.6 nmol/kg(LBm). min/pmol(INSULI N)/liter, P = 0.04); values improved at month 6 (49.2 +/- 22.6, P = 0.03, c ompared with month 1) and did not differ significantly from baseline. Simil arly, the integrated response to an oral glucose load worsened at month I ( glucose area under the curve 20.1 +/- 2.3 to 24.6 +/- 3.7 mmol .h/liter, P < 0.01), whereas values improved at month 6 (22.1 +/- 1.5, P = 0.02, compar ed with month 1) and did not differ significantly from baseline. One patien t developed symptomatic hyperglycemia within 2 wk of GH initiation; baselin e oral glucose tolerance testing revealed preexisting diabetes despite norm al fasting glucose. In conclusion, GH at 3 mg/d resulted in a decrease in t otal body fat and an increase in lean body mass in this open-label trial. W hile insulin sensitivity and glucose tolerance initially worsened, they sub sequently improved toward baseline. However, the dose of GH used in this tr ial was supraphysiologic and led to an increase in IGF-I levels up to three times the upper normal range. Because there are known adverse effects of l ong-term GH excess, the effectiveness of lower doses of GH should be studie d. We also recommend a screening oral glucose tolerance test be performed t o exclude subjects at risk for GH-induced hyperglycemia.