HIV This Week

Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A. Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using International Diabetes Foundation and Adult Treatment Panel III Criteria: Associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive peptide, and hypoadiponectinemia. Diabetes Care 2007;30:113-19.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes. Definitions exist to identify those "at risk." Treatment of HIV infection with highly active antiretroviral therapy can induce severe metabolic complications including lipodystrophy, dyslipidemia, and insulin resistance. Samaras and colleagues report the prevalence of metabolic syndrome in HIV-infected patients and compare insulin resistance and total body, limb, and visceral fat and adipokines in those with and without metabolic syndrome in an international cross-sectional study of a well-characterized cohort of 788 HIV-infected adults recruited at 32 centres. Metabolic syndrome prevalence was examined using International Diabetes Federation (IDF) and U.S. National Cholesterol Education Program Adult Treatment Panel III (ATPIII) criteria, relative to body composition (whole-body dual-energy X-ray absorptiometry and abdominal computed tomography), lipids, glycemic parameters, insulin resistance, leptin, adiponectin, and C-reactive protein (CRP). The prevalence of metabolic syndrome was 14% (n=114; 83 men) by IDF criteria and 18% (n=139; 118 men) by ATPIII criteria; the concordance was significant but only moderate (kappa = 0.46, P<0.0001). Many patients (49%) had at least two features of metabolic syndrome but were not classified as having metabolic syndrome as their waist circumferences or waist-to-hip ratios were in the non-metabolic syndrome range. Metabolic syndrome was more common in those currently receiving protease inhibitors (P=0.04). Type 2 diabetes prevalence was five-to-nine folds higher in those with metabolic syndrome. With IDF criteria, subjects with metabolic syndrome showed disturbances in inflammation and adipokines: they had higher C-reactive protein (P<0.003) and leptin (P<0.0001) and lower adiponectin (P<0.0001) levels. By ATPIII criteria, those with metabolic syndrome had higher leptin (P=0.006) and lower adiponectin (P<0.0001) levels. The authors conclude that metabolic syndrome prevalence in HIV-positive adults was lower than that reported for the general population. Metabolic syndrome was associated with a substantially increased prevalence of type 2 diabetes in this specific cohort. Many subjects without metabolic syndrome had at least two metabolic syndrome components but did not meet waist circumference or waist-to-hip ratio cut-off metabolic syndrome criteria in this group with high rates of body fat partitioning disturbances.

 Editors’ note: Although the prevalence of metabolic syndrome is not higher among people living with HIV in this general population known for its levels of obesity, it is nonetheless an unwanted side effect of some antiretroviral drugs and a risk factor for diabetes (see next article). A balanced diet and exercise are important prevention measures for everyone, living with HIV or not.

Hruz PW. Molecular mechanisms for altered glucose homeostasis in HIV infection. Am J Infect Dis 2006;2:187-192. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17186064

A complete understanding of the molecular mechanisms leading to HIV-associated insulin resistance remains elusive. Complex interrelationships between genetic predisposition, disease-related body changes and multi-drug therapy all contribute to alterations in glucose homeostasis. These abnormalities can be differentiated between acute and reversible changes directly induced by ART and more chronic and less reversible changes due to the development of lipodystrophy and hyperlipidaemia. Implicated pathways include changes in adipokine secretion, insulin signalling, lipid homeostasis and disease-related increases in inflammatory mediators. The insulin responsive facilitative glucose transporter GLUT4 is the first molecule to have been identified as a direct target of HIV protease inhibitors. Efforts to elucidate the mechanisms directly responsible for the evolution of insulin resistance during HIV infection and therapy will be greatly assisted by the further identification and characterization of direct molecular targets amenable to pharmacologic therapy and/or the development of newer antiretroviral agents that do not adversely affect these target proteins.