Visceral adipose tissue returns to baseline after stopping therapeutic intervention with rHGH
31 December 2009. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRW) 11 Philadelphia 2009.
Simon Collins, HIV i-Base
Central fat accumulation remains one of the most distressing but least understood metabolic complications, with very limited management options.
Several studies have reported that recombinant Human Growth Hormone (rHGH) can reduce central visceral adipose tissue (VAT), although earliest studies at higher doses (4-6 mg/day) were associated with significant toxicity. Additionally, any benefit seemed dependent on maintaining treatment, and the optimal dose remained to be established.
It was important to see the 3-years results from a study from the Massachusetts General Hospital, presented by Steven Grinspoon, carried out in people with reduced growth hormone (GH) secretion (peak GH <7.5 ng/mL). [1] This was a randomised double-blind study of low dose rHGH (an average dose of 0.33 mg/day: starting at 2 mcg/kg/day but increasing to 6 mcg/kg/day, titrating to the upper quartile of normal IGF-1 range). After 18 months patients crossed over to either active drug or placebo, depending on their original randomisation. The 18 month initial results have already been published. [2]
Pooled analysis for both arms showed that 18 months treatment significantly reduced mean (+SD) VAT compared to placebo (-7.3 +21.3% vs +4.8 +22.7%, p<0.0001) and trunk fat (-3.2 +15.3% vs +2.4 +13.1%, p=0.003). rHGH also had a statistically positive effect on reducing systolic and diastolic blood pressure, triglycerides and LDL-cholesterol and increasing lower limb fat, but had a negative glyceamic affect: increasing fasting glucose and 2-hour glucose on OGTT (see Table 1). No impact for seen for intima media thickness, though this was not elevated at baseline.
During the crossover period, the benefits of rHGH on VAT reversed to baseline within 6 months. The increase in IFG-1 seen during 18 month treatment (approximately +100ng/mL increase from baseline) also dropped within 2-4 weeks of discontinuation.
Table 1: Pooled effect of rHGH vs placebo at 18 months (mean%, ±SD)
| rHGH | placebo | p | |
| VAT | -7.3 ±21.3% | +4.8 ±22.7% | <0.0001 |
| Trunk fat | -3.2 ±15.3% | +2.4 ±13.1% | 0.003 |
| Lower limb fat | +4.9 ±13.3% | +1.1 ±11.8 | 0.03 |
| Systolic BP | -2.0 ±13.9% | +2.6 ±12.0% | 0.007 |
| Diastolic BP | -1.1 ±13.7% | +5.8 ±17.1% | 0.0009 |
| Triglycerides | -0.9 ±43.4% | +11.0 ±52.9% | 0.05 |
| LDL-chol | -2.7 ±23.7% | +4.9 ±28.7% | 0.03 |
| Fasting glucose | 6.7 ±11.7% | 2.5 ±11.4% | 0.007 |
| 2-hour glucose | 16.5 ±48.6% | 0.1 ±26.9% | 0.002 |
The importance of continuing treatment in order to maintain any reduction in VAT has also been reported with tesamorelin, which although has reduced toxicity, appears to reverse benefits back to baseline VAT levels if discontinued. An FDA decision on approval of tesamorelin is expected in the second quarter of 2010.
References
- Grinspoon S et al. Effects of treatment and discontinuation of low dose physiologic growth hormone in HIV patients with abdominal fat accumulation: a randomised, placebo-controlled 36-month crossover trial. 11th Intl Workshop on Adverse Drug Reactions. 26-28 October 2009, Philadelphia. Oral abstract O-02. Antiviral therapy 2009; 14 Suppl 2: A3.
- Lo et al. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation. JAMA 2008;300(5):509-519. (6 August 2008).
http://jama.ama-assn.org/cgi/content/full/300/5/509