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 accumulation, but the pharmacological doses (6 mg/d) used have been associated with impaired fasting glucose and hyperglycemia. In contrast, physiologic doses of GH ( approximately 1 mg/d) in HIV-negative men reduced visceral adiposity and eventually improved insulin sensitivity, despite initially causing insulin 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-associated fat accumulation. Oral glucose tolerance, insulin sensitivity, and body composition were measured at baseline, and 1 and 6 months. Six patients completed 1 month and 5, 6 months of GH therapy. IGF-I levels increased 4-fold within 1 month of GH treatment. Over 6 months, GH reduced buffalo hump size and excess visceral adipose tissue. Total body fat decreased (17.9 +/- 10.9 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-mediated glucose disposal, measured by a euglycemic hyperinsulinemic clamp, declined at month 1 (49.7 +/- 27.5 to 25.6 +/- 6.6 nmol/kg(LBM).min/pmol(INSULIN)/liter, P = 0.04); values improved at month 6 (49.2 +/- 22.6, P = 0.03, compared with month 1) and did not differ significantly from baseline. Similarly, the integrated response to an oral glucose load worsened at month 1 (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, compared with month 1) and did not differ significantly from baseline. One patient developed symptomatic hyperglycemia within 2 wk of GH initiation; baseline oral glucose tolerance testing revealed preexisting diabetes despite normal fasting glucose. In conclusion, GH at 3 mg/d resulted in a decrease in total body fat and an increase in lean body mass in this open-label trial. While insulin sensitivity and glucose tolerance initially worsened, they subsequently improved toward baseline. However, the dose of GH used in this trial 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 long-term GH excess, the effectiveness of lower doses of GH should be studied. We also recommend a screening oral glucose tolerance test be performed to exclude subjects at risk for GH-induced hyperglycemia.
Lo
J C
JC
Division of Endocrinology, Department of Medicine, University of California-San Francisco, San Francisco, California 94143, USA. jlo@itsa.ucsf.edu
Mulligan
K
K
Noor
M A
MA
Schwarz
J M
JM
Halvorsen
R A
RA
Grunfeld
C
C
Schambelan
M
M
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000187:drug effects*; D001824:Body Constitution; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I