Searching for the Skinny on Lipodystrophy
A Ground-breaking Study Looks at the Causes and Cures for this Dangerous Side Effect
Most of us are very familiar with the cluster of problems referred to as lipodystrophy; too familiar in fact. Faced with the prospects of body fat redistribution, increases in blood fats, and insulin resistance, some people are reluctant to start on anti-HIV drugs. However, several reports presented at conferences that cite examples of lipodystrophy in people who have not been on HAART, so what IS causing this problem? A new study beginning at the University of Washington may provide some answers.
The study has three unique goals: to determine the mechanisms that cause lipodystrophy, to help predict who would be most at risk of developing this condition, and to identify possible treatments. The study was designed and will be conducted by two endocrinologists (specialists in glands and hormones), Scott Weigle MD and Jonathan Purnell MD. They will have assistance from infectious disease specialist Thomas Hooton, Medical Director of the Madison Clinic at Harborview Medical Center. Drs Weigle and Purnell have conducted many studies on the mechanisms of obesity and fat distribution in HIV-negative people.
The researchers are working from the hypothesis that protease inhibitors cause the metabolic changes of lipodystrophy. They will investigate two possible mechanisms: increased cortisol (a hormone which regulates fat metabolism) in body tissues, and increased rates of fat cell development in the abdomen. Previous studies have shown that production of cortisol is closely linked with intra-abdomial fat in individuals without HIV infection. If the hypothesis is correct, people who develop lipodystrophy will have increased levels of cortisol production (known as hypercortisolism) or increased tissue sensitivity to cortisol. In the new study, participants will have cortisol production rates checked at their first visit to establish a baseline, and then at 2 and 12 months. If the assumptions are correct, people with elevated cortisol production at 2 months will begin to see an increase in abdominal fat and a reduction in peripheral fat (normally found in the face, arms, and legs) between 6 and 12 months.
Researchers are hoping that it may be possible to use cortisol production levels to predict who is a risk for lipodystrophy as soon as 2 months after beginning therapy. If hypercortisolism is found to impact lipodystrophy, there is drug therapy capable of lowering cortisol production that might be used prevent lipodystrophy in people at risk.
Researchers are also investigating another way that HAART might trigger lipodystrophy, by monitoring the activity of a hormone receptor sometimes referred to as the "master switch" for fat development. The master switch is called peroxisome proliferator-activated receptor gamma 2, abbreviated PPARy2. The study will investigate whether protease inhibitors lead to increased levels of PPARy2 in the abdomen, as compared to the arms, legs and face. This would cause pre-fat cells in the abdomen to mature in to fat cells at a much higher rate. If this hypothesis proves correct, medications that lower PPARy2 levels might be used to prevent lipodystrophy.
The study will be recruiting participants for 3 years, with the goal of recruiting a total of 180 people. Participants will be followed for 1 year and will need to spend 2 nights in the hospital on three occasions and to make one half-day visit. While in the hospital participants will have a constant intravenous line to draw blood to check cortisol and insulin levels. Participants will also have total body and abdominal fat content measured by both dual-energy X-ray absorptiometry (DEXA) and computerized tomographic (CT) scanning. Biopsies will also be performed on fat tissue collected from the leg and stomach by inserting a 16-gauge needle under the skin. (The researchers swear this doesn't hurt.) To compensate people for participating in the trial, $100 is offered for each study day, for a total of $1,000 for completion of 10 study days over 1 year!
If you are interested in joining the study, please see ad on page 18, or contact Pat Breen RN at (206) 731-6749.
The problem of lipodystrophy continues to be a concern when considering long-term drug therapy. It is crucial that the mechanism and cause of lipodystrophy be determined so that preventive therapy can be developed.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Perspective.