Low-Dose Growth Hormone in HIV Positive Men with Fat Accumulation Reduces Total Body Fat and Increases Lean Body Mass                                                               

Since the advent of HAART, HIV positive patients, male and female, have experienced significant body composition changes that have adversely impacted their quality of life.

Researchers have noted various syndromes of altered fat distribution, including fat accumulation in the dorsocervical region and abdomen of HIV positive patients. There are also growing concerns that these complications may increase the risk for insulin resistance and cardiovascular disease.

Prior studies have shown that growth hormone (GH) reduces HIV-associated fat accumulation but may worsen glucose metabolism. Researchers at UCSF, UCLA and the San Francisco Department of Veterans Affairs Medical Center investigated the effects of a low dose of GH (1 mg per day) in HIV-infected men with fat accumulation. They found that the treatment reduced total fat and increased lean body mass (LBM) without significant changes in glucose tolerance or insulin sensitivity.

Visceral adipose tissue (VAT) levels did not change significantly for the group as a whole, although a reduction in the VAT level was seen in patients with a greater VAT level at baseline.

The average magnitude of fat loss was slightly more than one-half that seen in a previous study of GH at 3 mg per day, consistent with more modest effects of the lower dose on lipid oxidation. In the present study, lipid oxidation increased by only 16%, whereas it increased by 84% in patients treated with GH at 3 mg per day (P < .001).

It is interesting that, in both the current and prior studies, patients who lost VAT during GH treatment had the largest amount of VAT at baseline. Thus, it is possible that the level of baseline VAT is a factor in determining the amount of VAT reduction with GH.

The broad range of intra-abdominal fat content, despite a waist-to-hip ratio >0.95 and a waist circumference >90 cm, may have contributed to the variable response of VAT to GH in these patients. Future studies should consider whether there are additional anthropometric criteria to better identify patients with increased VAT (or perhaps excess VAT should be used as an entry criterion), because these individuals may benefit most from GH therapy.

In addition, the optimal dose and duration of treatment needs to be determined. For example, in HIV-seronegative men with abdominal obesity, an even lower dosage of GH (e.g., 9.5 g/kg per day) over a longer treatment period was effective in reducing visceral adiposity and in improving glucose and lipid metabolism.

Changes in appendicular fat were not observed in this study, nor were they observed in the prior pilot study, although further loss of subcutaneous fat with GH treatment is a potential concern in patients with peripheral lipoatrophy.

Other studies have shown that appendicular fat stores may be reduced with GH treatment, and it is possible that a similar effect will be evident after a longer period of GH treatment, despite the lower dose.

In contrast to a dosage of 3 mg per day, the effects of GH at 1 mg per day on glucose metabolism were more modest and not statistically significant. However in 3 patients in the current study, IGF-1 levels reached the supraphysiologic range, and 1 patient developed carpal tunnel syndrome, requiring cessation of treatment.

^“Thus,” write the authors, “prolonged GH treatment, even at this lower dosage, should be considered cautiously, given the adverse consequences of long-term GH excess.”

In summary, the authors note, “The results of this pilot study suggest that treatment with GH at a dose of 1 mg per day reduces total body fat and increases LBM without significant adverse effects on glucose metabolism.”

“These results need to be confirmed in a larger randomized study. Additional studies are also needed to determine whether this dose of GH is effective in reducing VAT, particularly in patients with documented high visceral fat content.”

Department of Medicine, University of California at San Francisco, Division of Endocrinology, San Francisco General Hospital, and Metabolism and Endocrine Sections, San Francisco Department of Veterans Affairs Medical Center, San Francisco, and Department of Nutritional Sciences, University of California at Berkeley, California.

09/03/04

References

J C Lo and others. The Effects of Low-Dose Growth Hormone in HIV-Infected Men with Fat Accumulation: A Pilot Study. Clinical Infectious Diseases 39:732-735. September 1, 2004.

J C Lo, K Mulligan, M A Noor, et al. The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation. J Clin Endocrinol Metab 86: 34803487. 2001.