Effect of Recombinant Human Growth Hormone in the Treatment of Visceral Fat Accu

[Guest guest]

Journal of Acquired Immune Deficiency Syndromes

August 1, 2002 (Volume 30, Number 4)

Effect of Recombinant Human Growth Hormone in the Treatment of Visceral Fat Accumulation in HIV InfectionEngelson ES, Glesby MJ, Mendez D, et al.

Journal of Acquired Immune Deficiency Syndromes. 2002;30(4):379-391

The authors enrolled 26 men and 4 women, all clinically stable and receiving stable antiretroviral therapy, who were experiencing truncal obesity in an open-label study of 24 weeks of high-dose recombinant human growth hormone (rhGH; 6 mg/day) followed by a 12-week washout period and an optional further 24 weeks of low-dose rhGH (4 mg/day on alternate days). Dual-energy x-ray absorptiometry (DEXA) scans were used to determine total body fat and lean tissue, and MRI scans to determine total body visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle mass. Metabolic measurements were taken and subjective quality-of-life questionnaires were self-administered.After 12 weeks of high-dose rhGH, no changes were seen in mean body weight or body mass index, but VAT volume decreased by an average of 42% and SAT volume decreased by approximately 10%. VAT decreased by a further 15% between weeks 12 and 24, but this was not statistically significant. The effects of rhGH reversed after discontinuation of therapy. There were trends towards reductions in SAT and VAT in patients who resumed therapy with low-dose rhGH, but these did not reach statistically significance. Fasting glucose levels increased significantly in patients receiving rhGH at either dose level, and 4 participants developed diabetes during the trial (3 on high-dose, 1 on low-dose rhGH). Fasting triglyceride levels increased initially and then returned to baseline.Adverse effects were frequent and discontinuation and dropout rates were high. Three participants withdrew from the trial early due to self-perceived lack of efficacy, 4 withdrew due to musculoskeletal stiffness/pain, 4 due to paresthesias/carpal tunnel syndrome, and a further 6 due to other events, although 2 were for non-rhGH-related carcinomas. A further 6 patients required dose reductions. The major effect on quality of life was an increase in body pain after 12 weeks of high-dose rhGH; there were no changes in quality of life measurement on low-dose rhGH.Growth hormone is emerging as an attractive treatment for some aspects of the lipodystrophy syndrome. The benefits of growth hormone are particularly evident with regard to reducing visceral adiposity. Unfortunately, in this and some other studies, the benefits of growth hormone appear to be lost after the drug is discontinued. There are also drawbacks, including cost, problems with increased glucose intolerance, concern regarding increased risk of malignancy, and more modest adverse events such as musculoskeletal pain and stiffness. Some other agents have been observed to reduce visceral adiposity, most notably the insulin sensitizer metformin. It would therefore seem appropriate to initiate combination studies of metformin with growth hormone to see whether more sustained reductions of VAT and reduced numbers of individuals developing glucose intolerance are observed (GM).

Effect of Recombinant Human Growth Hormone in the Treatment of Visceral Fat Accumulation in HIV Infection

Ellen S. Engelson*; §Marshall J. Glesby; § Mendez; †Jeanine B Albu; ‡Jack Wang; ‡ B. Heymsfield; * P. Kotler

*Gastrointestinal Division, †Division of Endocrinology and Metabolism, Obesity Research Center, and the ‡Body Composition Unit, Department of Medicine, St. Luke's–Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York; and §Community Research Initiative on AIDS, New York, New York, U.S.A.

Dr. Glesby's current affiliation is Weill Medical College of Cornell University, New York, New York, U.S.A.

JAIDS JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 2002;30:379-391

HIV-associated lipodystrophy often includes excess accumulation of visceral fat. Recombinant human growth hormone (rhGH) is a potential treatment for the excess visceral fat. Prospective, open-label trials of 24 weeks of rhGH 6 mg/d and 24 weeks of 4 mg every other day were conducted with an intervening washout period of 12 weeks. Thirty HIV-positive participants (26 men and 4 women) with visceral adiposity were enrolled. The main outcome measure was change in visceral adipose tissue (VAT) on whole-body magnetic resonance imaging scan. Changes in whole-body subcutaneous adipose tissue and skeletal muscle, glucose metabolism, serum lipids, and quality of life were also assessed. Despite stable body weight, VAT decreased in evaluable subjects an average of 42% with rhGH 6 mg/d (n = 24; p < .001) and 15% with 4 mg every other day (n = 10; p < .01) after 12 weeks, with trends toward further decreases after an additional 12 weeks at each dose. Subcutaneous adipose tissue also decreased, but proportionately less and not significantly on the lower dose. Skeletal muscle increased. Body composition rebounded to or near baseline after the washout period. Effects on lipids were inconsistent. Total cholesterol levels fell on the higher dose only, whereas high-density lipoprotein cholesterol levels increased on the lower dose only, and there was no effect on triglyceride levels. Joint pain was the most common adverse event, and was reflected in subjective quality of life measurements as an increase in bodily pain. Insulin sensitivity fell, and 4 participants developed diabetes. Other adverse events included cancer of unknown relationship to treatment in 3 participants. Levels of distress decreased after 24 weeks on the higher dose. In conclusion, rhGH effectively reduces the excess visceral adipose tissue often associated with HIV fat redistribution/lipodystrophy. However, frequent adverse effects warrant controlled studies and careful patient monitoring, especially regarding glucose tolerance.

Key Words: HIV; Growth hormone; Lipodystrophy; Clinical trials; Body composition; Glucose tolerance; Lipids; Quality of life

Vergel

Executive Director

Program for Wellness Restoration, PoWeR

www.medibolics.com

www.facialwasting.org

lipodystrophy (subscribe by sending email to

lipodystrophy-subscribe )

"Nothing in the world can take the place of persistence. Talent will not; nothing is more common than unsuccessful people with talent. Genius will not; unrewarded genius is almost a proverb. Education will not; the world is full of educated derelics. Persistence and determination are omnipotent." Calvin Coolidge, 30th President of the US