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Rosiglitazone Improves Postprandial Triglyceride and Free Fatty Acid Metabolism in Type 2 Diabetes

¹ Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
² Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands
³ Department of Internal Medicine, St. Franciscus Gasthuis, Rotterdam, The Netherlands
⁴ Department of Nephrology and Hypertension, Leiden University Medical Center, Leiden, The Netherlands

Address correspondence and reprint requests to Jeroen P.H. van Wijk, MD, Department of Internal Medicine, University Medical Center Utrecht, Room G02.402, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: j.p.h.vanwijk{at}azu.nl

OBJECTIVE—Increased postprandial lipemia is part of diabetic dyslipidemia and is associated with accelerated atherosclerosis. We investigated the effects of the peroxisome proliferator–activated receptor- agonist rosiglitazone on postprandial lipemia in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A randomized, 8-week, crossover, placebo-controlled, 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 ± 0.22 vs. 1.88 ± 0.20 mmol/l, respectively) but decreased postprandial triglyceride levels, leading to significantly lower triglyceride dAUC (–37%, P < 0.05), without changing total triglyceride AUC. Significant postprandial triglyceride reductions in the chylomicron fraction (Svedberg flotation rate [Sf] >400) were achieved with rosiglitazone, which resulted in a significant lower triglyceride AUC (–22%) in this fraction. The postprandial triglyceride increase in VLDL1 (Sf 60–400) was also lower after rosiglitazone (–27%), 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 (–12%) and FFA dAUC (–18%) 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.

Abbreviations: ALT, alanine transferase • apoB, apolipoprotein B • AST, aspartate aminotransferase • AUC, area under the curve • dAUC, incremental AUC • FFA, free fatty acid • LPL, lipoprotein lipase • PPAR-, peroxisome proliferator–activated receptor- • TRL, triglyceride-rich lipoprotein • TZD, thiazolidinedione

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