Growth hormone treatment for HIV patients improves abdominal fat, but worsens glucose level

For human immunodeficiency virus (HIV)-infected patients with treatment-related abdominal obesity and growth hormone deficiency, receiving low-dose growth hormone resulted in improvement in fat and blood pressure measurements but worsened glucose levels, according to a study in the August 6 issue of JAMA, a theme issue on HIV/AIDS.

Steven Grinspoon, M.D., of Massachusetts General Hospital, Boston, presented the findings of the study at a JAMA media briefing on HIV/AIDS.

Patients with HIV infection treated with antiretroviral therapy frequently develop changes in body composition, such as abdominal obesity, and metabolic complications of dyslipidemia (disorders of lipoprotein metabolism, including high cholesterol levels) and insulin resistance, putting these patients at increased cardiovascular risk. Growth hormone (GH) secretion is reduced in patients with HIV and abdominal fat accumulation, and relative GH deficiency (GHD) is observed in approximately one-third of such patients, according to background information in the article. Some studies have indicated that doses of growth hormone could decrease abdominal fat.

Dr. Grinspoon and colleagues conducted a study to determine whether low-dose GH in 56 HIV patients with abdominal fat accumulation and GH deficiency would improve body composition, lipids, and other metabolic and cardiovascular measures. Patients were randomly assigned to receive by injection either GH or matching placebo. Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses.

The researchers found that abdominal fat decreased significantly in the GH group compared with the placebo group, with a percentage change in the GH group of −8.5 percent and −1.6 percent in the placebo group. Trunk-to-lower extremity fat ratio and trunk fat also decreased in the GH group compared with the placebo group.

Triglycerides and diastolic blood pressure (BP) levels improved with GH, while the change in systolic BP was not statistically different compared with placebo. Total cholesterol and high density lipoprotein (HDL) cholesterol levels were unchanged between the two groups. GH increased glucose levels during glucose tolerance testing, however long-term indices of glucose, hemoglobin A1c (the substance of red blood cells that carries oxygen to the cells and sometimes joins with glucose), were not different between the groups.

"Data from our randomized, placebo-controlled trial involving a long duration of observation inject a note of caution into the debate regarding the use of GH therapy in the HIV population," the authors write. "Low-dose physiological GH is well-tolerated and results in significant but more modest reduction in visceral adipose tissue [VAT; abdominal fat], but is nonetheless associated with increased glucose levels. Therefore, the therapeutic window to achieve an optimal risk-benefit ratio of GH in individuals with HIV, abdominal fat accumulation, and insulin resistance may be very narrow and difficult to achieve."

"Growth hormone is not yet FDA-approved for the treatment of abdominal fat accumulation in patients with HIV. Other more potent strategies to safely increase GH and reduce VAT, including the use of GH-releasing hormone (GHRH), may be more beneficial. In addition, strategies using diet, exercise, and lifestyle change may be more cost-effective in the long run than GH, particularly in patients with HIV, visceral adiposity, and insulin resistance, in whom changes in glucose may be counterproductive," the researchers conclude.
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(JAMA. 2008;300[5]:509-519. Available pre-embargo to the media at www.jamamedia.org) Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

RESOURCE/SOURCE: http://www.eurekalert.org/pub_releases/2008-08/jaaj-ght073108.php on Sunday, August 3, 2008.

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