The findings emphasize the importance of individualized care in HIV-infected patients. Although rosiglitazone may partly correct lipoatrophy, metformin improves visceral fat accumulation, fasting lipid profile, and endothelial function.

Abstract-We evaluated study population characteristics and treatment effects on blood lipids between studies in which either rosiglitazone (RSG) or pioglitazone (PIO) was investigated in patients with type 2 diabetes. We performed a summary analysis of all published double-blind, placebo-controlled studies with RSG (4 and 8 mg/d) and PIO (15,30, and 45 mg/d). Data were analyzed by the random-effects model. Nineteen trials met our inclusion criteria, yielding 5304 patients, 3236 in studies with RSG and 2068 in studies with PIO. Subjects treated with PIO were more obese and showed more pronounced hyperglycemia and dyslipidemia (increased triglycerides and decreased HDL cholesterol) at baseline than did subjects treated with RSG. By weighted linear-regression analysis, studies with PIO showed greater beneficial effects on triglycerides, total cholesterol, and LDL cholesterol, after adjustment for the respective lipid levels at baseline.

The data of the present study suggest an increased cardiovascular risk in HIV-infected patients, even in the absence of clustering of metabolic risk variables. The presence of the MS in HIV is associated with even more advanced atherosclerotic changes. Presumably, both HIV infection and antiretroviral therapy may promote atherosclerosis through mechanisms involving endothelial cells, either directly or indirectly via metabolic risk factors.

The use of combination antiretroviral therapy (CART) in HIV-infected patients has resulted in a dramatic decline in AIDS-related mortality. However, mortality due to non-AIDS conditions, particularly cardiovascular disease (CVD) seems to increase in this population. CART has been associated with several metabolic risk factors, including insulin resistance, low HDL-cholesterol, hypertriglyceridemia and postprandial hyperlipidemia. In addition, HIV itself, as well as specific antiretroviral agents, may further increase cardiovascular risk by interfering with endothelial function. As the HIV population is aging, CVD may become an increasingly growing health problem in the future. Therefore, early diagnosis and treatment of cardiovascular risk factors is warranted in this population. This paper reviews the contribution of both, HIV infection and CART, to insulin resistance, postprandial hyperlipidemia and cardiovascular risk in HIV-infected patients. Strategies to reduce cardiovascular risk are also discussed.

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OBJECTIVE -Increased postprandial lipemia is part of diabetic dyslipidemia and is associated with accelerated atherosclerosis. We investigated the effects of the peroxisome proliferatoractivated receptor-␥ agonist rosiglitazone on postprandial lipemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A randomized, 8-week, crossover, placebocontrolled, double-blind trial was performed in which rosiglitazone at 4 mg was administrated twice daily in 19 patients with type 2 diabetes. Standardized 6-h oral fat-loading tests were performed after each treatment period. Postprandial curves were calculated as the total area under the curve (AUC) and the incremental area under the curve (dAUC).RESULTS -Rosiglitazone did not change fasting plasma triglycerides compared with placebo (1.97 Ϯ 0.22 vs. 1.88 Ϯ 0.20 mmol/l, respectively) but decreased postprandial triglyceride levels, leading to significantly lower triglyceride dAUC (Ϫ37%, P Ͻ 0.05), without changing total triglyceride AUC. Significant postprandial triglyceride reductions in the chylomicron fraction (Svedberg flotation rate [Sf] Ͼ400) were achieved with rosiglitazone, which resulted in a significant lower triglyceride AUC (Ϫ22%) in this fraction. The postprandial triglyceride increase in VLDL1 (Sf 60 -400) was also lower after rosiglitazone (Ϫ27%), but this did not result in a significant lower triglyceride AUC. In VLDL2 (Sf 20 -60), there were no significant differences in triglyceride AUC and triglyceride dAUC between rosiglitazone and placebo. Rosiglitazone decreased free fatty acid (FFA) AUC (Ϫ12%) and FFA dAUC (Ϫ18%) compared with placebo.CONCLUSIONS -Rosiglitazone improves the metabolism of large triglyceride-rich lipoproteins and decreases postprandial FFA concentrations in type 2 diabetes. This may have clinical implications, as these effects may contribute to cardiovascular risk reduction. Diabetes Care 28:844 -849, 2005D yslipidemia is one of the main cardiovascular risk factors in type 2 diabetes (1). An increased hepatic free fatty acid (FFA) flux has been postulated as a major contributor of diabetic dyslipidemia because it could lead to hepatic overproduction of triglyceride-rich lipoproteins (TRLs) (1). It is important to realize that humans are nonfasting most of the day and that nonfasting triglycerides are also predictors of atherosclerosis (2). Exaggerated and prolonged postprandial hyperlipidemia is an important characteristic of diabetic dyslipidemia (1-3). Several studies have shown that, even in fasting normolipidemic subjects, impaired clearance of TRL and their remnants is linked to atherosclerosis (4 -9). Therefore, therapeutic modulation of postprandial lipemia may convey increased protection from atherosclerosis.Thiazolidinediones (TZDs) are oral antihyperglycemic agents that reduce insulin resistance in peripheral tissues and decrease hepatic glucose production (10). TZDs are potent synthetic ligands for peroxisome proliferator-activated receptor-␥ (PPAR-␥) activation, thereby directly influencing the transcription of gen...

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.

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