September 30, 2006
Morphologic abnormalities continue to be a significant problem in patients with HIV disease. Fat loss syndromes appear to be closely linked to the use of nucleoside reverse transcriptase inhibitors (NRTIs) and at least partially responsive to changes in therapy. Less is known regarding the pathogenesis or optimal management strategy for those with fat accumulation syndromes. Increased visceral fat can be a particularly significant problem, both from a cosmetic perspective and from a health perspective given its association with physical complaints such as gastroesophageal reflux and respiratory compromise. It is also known that, in the general population, visceral adiposity is an independent predictor of cardiovascular disease.
Several interventions for reducing visceral fat have been tested with variable results. Perhaps the best data come from case series and randomized controlled clinical trials assessing the use of recombinant human growth hormone (r-hGH). The rationale for using this agent is that it is lipolytic. Yet, although r-hGH may reduce visceral fat, there is concern that it could also increase subcutaneous fat loss and exacerbate lipoatrophy.
Markus Bickel, from Goethe University in Frankfurt, Germany, and colleagues previously reported data obtained from 26 HIV-infected adults with clinical symptoms of fat accumulation while on an unchanged antiretroviral regimen for at least three months.1 These individuals were randomized to receive r-hGH at a dose of 4 mg subcutaneously either daily or three times per week for 12 weeks followed by 2 mg subcutaneously per day for an additional 12 weeks. An MRI scan was used to assess fat distribution in these patients during the initial 24 weeks of follow-up. The individuals showed marked reductions in visceral fat at 12 weeks that did not significantly differ by dosing schedule, and these reductions were maintained during the second 12 weeks of lower dose therapy. There was a small, concomitant reduction in limb and facial fat also reported across the groups at both 12 and 24 weeks. The investigators further reported increases in high-density lipoprotein (HDL) cholesterol and fasting insulin levels.
In the current study, Bickel et al summarized long-term follow-up data from a subset of the original 26 study participants.2 The substudy included 15 men and one woman from the original trial who had undergone six to 12 months of follow-up assessment after completion of the low-dose r-hGH maintenance phase of the study. Serial MRI scans were performed to assess visceral fat, mid-thigh fat and facial fat. Select metabolic parameters were also monitored over time.
The changes in these measures are summarized in the table below. Overall, there was a decrease in visceral fat, mid-thigh fat and facial fat during the treatment phase of the study. Although there was an increase in fat off therapy -- particularly in the visceral compartment -- the fat levels remained below baseline after a median of nine months of follow-up. In addition, the metabolic profile at follow-up was better than it was at baseline, particularly with regard to lower fasting glucose and triglyceride levels. It is suspected that the improved metabolic profile may stem from the reductions in visceral adipose tissue.
|Change in Body Fat and Metabolic Parameters Over Time|
|Parameter||Baseline||Week 12||Week 24||Follow-Up*|
|Fat Mass (cm2)|
|Visceral||121 + 70||78 + 49||68 + 37||94 + 53|
|Mid-Thigh||49 + 32||42 + 28||40 + 28||41 + 27|
|Face||15.0 + 6.1||11.9 + 5.8||11.7 + 5.5||12.6 + 6.2|
|Glucose||92 + 9||93 + 14||94 + 11||77 + 18|
|Triglycerides||286 + 133||246 + 128||245 + 115||214 + 100|
|LDL||132 + 27||116 + 31||126 + 29||132 + 25|
|HDL||42 + 7||46 + 10||45 + 11||45 + 12|
The investigators of this study concluded that the initial response to r-hGH is consistent with that seen in other studies. Especially encouraging was the observation that thrice-weekly dosing, in comparison with daily dosing, achieved significant reductions in visceral fat, which were then maintained with 2 mg daily dosing.
This small study also showed that although fat re-accumulation occurred off treatment, visceral fat content still remained below baseline levels after a median of nine months off r-hGH. Not surprisingly, the investigators found that the lipolytic effects of r-hGH also extended to limb and facial fat; however, the degree of the observed fat loss is of unknown clinical significance.
Much larger studies have recently been reported that address the safety and efficacy of r-hGH in this patient population. The addition of pilot data on longer term follow-up and the effects on fat in other areas, particularly the face, will be relevant if this treatment strategy becomes more widely adopted in the future.
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