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Treatment of Lipodystrophy with Troglitazone
- Elif Arioglu, MD; and
- Simeon I. Taylor, MD, PhD
- National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch; Bethesda, MD 20892-1829 (Arioglu, Taylor)
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IN RESPONSE:
There are many unanswered questions about the relationship between insulin resistance and the distribution of body fat. Under most circumstances, increases in the content of visceral body fat are correlated with insulin resistance. Indeed, as noted by Dr. Cheng, a marked increase in visceral body fat has been reported in HIV-infected patients treated with highly active antiretroviral therapy, including protease inhibitors, and this abnormal fat distribution (HIV lipodystrophy) may be the cause of insulin resistance (1-3). The hyperinsulinemia seen in these patients is probably secondary, resulting from homeostatic mechanisms that attempt to compensate for the insulin resistance. The primary causes of HIV lipodystrophy have not been elucidated at the molecular level. Although it is possible that the secondary hyperinsulinemia observed in these patients may lead to a vicious cycle by exacerbating the tendency to accumulate visceral fat, it is unlikely that hyperinsulinemia is the primary cause of the lipodystrophy. The patients in our study did not have HIV lipodystrophy. Indeed, most had genetic forms of disease in which lipoatrophy was the primary defect leading to insulin resistance. When the study was initiated, we hypothesized that defects in adipogenesis might have contributed to the paucity of fat in some of our patients. Accordingly, we initiated therapy with troglitazone, a drug that has been demonstrated to promote adipogenesis in vitro by a mechanism mediated by peroxisome proliferator-activated receptor-γ. Consistent with that hypothesis, therapy with troglitazone led to a statistically significant increase in body fat, suggesting that the rate of triglyceride synthesis exceeded the rate of fat oxidation. As pointed out by Dr. Cheng, it is therefore paradoxical that troglitazone led to a decrease in the respiratory quotient. It is not clear how to resolve this paradox. However, it is important to remember that we did not monitor respiratory quotient throughout the day. We observed that respiratory quotient was decreased when it was measured after an overnight fast, which indicates that the fractional rate of fat oxidation increased or the rate of lipogenesis decreased during the fasting state. Thus, we can speculate that fat accumulated as a result of net lipogenesis, which presumably occurred in response to meals at a time when we did not measure respiratory quotient.
Elif Arioglu, MD
Simeon I. Taylor, MD, PhD
National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch; Bethesda, MD 20892-1829
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
