By Ed Susman
MEXICO CITY -- August 4, 2008 -- While low-dose treatment with human growth hormone appears to meaningfully reduce visceral fat accumulation in patients with human immunodeficiency virus (HIV) who have developed signs of lipodystrophy, the treatment appears to cause a subgroup of patients to show increased signs of glucose intolerance, according to findings presented here at the 17th International AIDS Conference (AIDS 2008).
"These data inject a note of caution into the debate regarding the use of growth hormone in HIV," said one of the study authors, Steven Grinspoon, MD, Harvard Medical School, Boston, Massachusetts, speaking August 3 at a media briefing held by the Journal of the American Medical Association (JAMA). "Even low-dose growth hormone, albeit effective in improving major cardiovascular risk measures and better tolerated than high-dose growth hormone, may increase specific glucose parameters."
After rigourous testing to determine eligibility -- aimed at identifying patients with HIV infection who also had low levels of growth hormone -- Dr. Grinspoon and colleagues assigned 26 patients to receive low-dose growth hormone by daily subcutaneous injection, while another 29 patients were assigned placebo.
The starting dose for those who received growth hormone was 2 mcg/kg/day for 18 months. That dose was titrated to a maximum dose of 6 mcg/kg/day. Dr. Grinspoon said that represented an average .33-mg/day dose, far below previous clinical trials in which dosages were as high as 4 mg and were associated with greater adverse side effects.
By the end of the trial, visceral fat had been reduced by approximately 9% among the patients on growth hormone, a level that is considered clinically meaningful by the US Food and Drug Administration, Dr. Grinspoon said. He said that lowering the dose further to avoid the problem of increased glucose tolerance would be unlikely to be effective.
"We found that the 18-month treatment resulted in significantly reduced visceral adipose tissue (P = .049) and truncal obesity (P = .04), triglycerides (P = .002) and diastolic blood pressure (P = .006)," he said. "But 2-hour glucose levels on glucose-tolerance testing were increased (P = .009)."
Dr. Grinspoon noted that increases in fasting glucose -- even when glycated haemoglobin (Hb A1C) and insulin levels were unchanged -- still is a well-established risk factor for later development of diabetes.
Further scrutiny of the data determined that most of the patients who showed increases in fasting glucose had impaired glucose tolerance at baseline.
This study was funded by the US National Institutes of Health. It will appear this week in the HIV/AIDS-themed issue of JAMA on August 6, 2008.
[Presentation title: Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation.]
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