Treatment of HIV-infected individuals with PIs is associated with changes in body fat distribution and metabolic disturbances similar to those seen in syndrome X. PI use has been variably associated with hypertriglyceridemia, insulin resistance including diabetes mellitus and the development of central obesity which is often accompanied by loss of fat from the extremities and buttocks. It is unclear how these complications relate to each other. Based on the experience of patients with syndrome X, it is highly probable that if these metabolic complications of PI therapy cluster, then they will in turn be associated with an increased risk of coronary artery disease. One hypothesis of this proposal is that patients who develop an increase in abdominal girth as well as those who develop hypertriglyceridemia without a clinically apparent change in body fat distribution will both have significantly more visceral fat and insulin resistance compared to controls. The investigators hypothesize that these changes represent one syndrome rather than several. To test this hypothesis, four groups of HIV-infected subjects will be compared: 1) PI-treated patients who have developed a """"""""protease paunch;"""""""" 2) PI-treated patients with hypertriglyceridemia but no clinically apparent change in body fat distribution; 3) PI-treated patients free of these two complications; and 4) PI-naive patients. Body composition and visceral adiposity will be determined by dual energy X-ray absorptiometry (DEXA) and computerized tomography, respectively. Insulin sensitivity will be measured using the frequently sampled intravenous glucose test (FSIGT). A prospective study is also planned to test the hypothesis that, after the initiation of PI therapy, a decline in insulin sensitivity will predict the development of visceral fat accumulation and, therefore, may be casual in its development. This is a unique opportunity to study the development of visceral obesity and its relationship to insulin resistance. Finally, the investigators hypothesize that the decrease in peripheral adipose tissue associated with PI therapy is due to increased mobilization or decreased storage of triglycerides (TGs)in those depots. Other potential mechanisms of adipose tissue loss including apoptosis and dedifferentiation will also be studied. The loss of peripheral fat stores offer a unique opportunity to determine the genes involved in regulating adipose tissue mass and distribution in general.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR016069-05
Application #
6763131
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2000-08-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
5
Fiscal Year
2004
Total Cost
$99,119
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Kosmiski, Lisa A; Bessesen, Daniel H; Stotz, Sarah A et al. (2007) Short-term energy restriction reduces resting energy expenditure in patients with HIV lipodystrophy and hypermetabolism. Metabolism 56:289-95
Bush, Zachary M; Kosmiski, Lisa A (2003) Acute pancreatitis in HIV-infected patients: are etiologies changing since the introduction of protease inhibitor therapy? Pancreas 27:e1-5
Kosmiski, Lisa A; Kuritzkes, Daniel R; Sharp, Teresa A et al. (2003) Total energy expenditure and carbohydrate oxidation are increased in the human immunodeficiency virus lipodystrophy syndrome. Metabolism 52:620-5
Kosmiski, Lisa; Kuritzkes, Daniel; Lichtenstein, Kenneth et al. (2003) Adipocyte-derived hormone levels in HIV lipodystrophy. Antivir Ther 8:9-15
Kosmiski, L; Kuritzkes, D; Hamilton, J et al. (2003) Fat distribution is altered in HIV-infected men without clinical evidence of the HIV lipodystrophy syndrome. HIV Med 4:235-40
Kosmiski, L A; Kuritzkes, D R; Lichtenstein, K A et al. (2001) Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome. AIDS 15:1993-2000