Metabolic Abnormalities and Cardiovascular Disease Risk Factors in Adults with Human Immunodeficiency Virus Infection and Lipodystrophy

Abstract

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy

“…Although we did not find a significant association between current protease inhibitor or thymidine analogue use and insulin resistance, brachial FMD, or CIMT, the use of specific antiretrovirals has been strongly associated with insulin resistance in other studies [3,4,[20][21][22]27,28]. The development of insulin resistance in some patients on HAART may have important long-term implications in determining cardiovascular disease risk.…”

“…Some antiretroviral therapies have been associated with insulin resistance, increased visceral fat deposition, and increases in atherogenic dyslipidemia, all components of the metabolic syndrome [3][4][5]. Recent evidence indicates that cumulative exposure to protease inhibitors over time is an independent risk factor for myocardial infarction (MI) in a large, ongoing observational study [2].…”

HIV infection, aging and cardiovascular disease: epidemiology and prevention

“…Studies have reported high frequencies of impaired glucose tolerance in patients with LDS or fat accumulation, for example, 35% are reported to have impaired glucose tolerance compared with 5% in healthy matched controls, and 7% are reported to have diabetes mellitus compared with 0.5% of healthy matched controls. 48 The presence of LDS has not been shown to be an independent risk factor for MI, 16 and it remains unclear whether dyslipidaemia worsens with age among HIV-positive patients. In the D:A:D study, rates of dyslipidaemia remained relatively stable for each calendar year between 2000 and 2006, 5 while data from the Veteran's Affair study reported dyslipidaemia to be more common among older HIV-positive patients who are also male and of white ethnicity.…”

Preferential loss of omental-mesenteric fat during growth hormone therapy of HIV-associated lipodystrophy

“…A substantial proportion of human immunodeficiency virus (HIV)-infected individuals on highly active antiretroviral therapy (HAART) develop fat redistribution, or HIV lipodystrophy, which is characterized by increased IAAT and/or depletion of subcutaneous adipose tissue (3)(4)(5). It is believed that fat redistribution affects long-term health outcomes by exacerbating the associated metabolic alterations (9,12), which is a rationale for its treatment. Studies have shown that growth hormone secretion is suppressed in HIV-positive or HIV-negative subjects with increased IAAT (24,25), and therapy with recombinant human growth hormone (rhGH) reduces IAAT contents (6,16,28).…”