Fasting and postprandial effects of rosiglitazone on low- and high-density lipoproteins size and subclasses in type-2 diabetes

Background: There is evidence that rosiglitazone may increase cardiovascular risk and, on this basis, this agent has been recently advised for treatment of type-2 diabetes. Yet, its effects on fasting and postprandial atherogenic dyslipidemia are still not fully elucidated. Methods: In an open-label study rosiglitazone (4 mg/day for 12 weeks) was added on top of a maximum of two oral antidiabetic drugs to 18 patients with adequately controlled type-2 diabetes (HbA1c: 6.5–8.0%), evaluating the effects on plasma lipids and lipoproteins before and after an oral fat load. Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) size and subclasses were determined by gradient gel electrophoresis. Results: Rosiglitazone improved HbA1c (P=0.0023), while no significant changes were found in plasma lipids or lipoprotein (a), both fasting and post-prandially. Fasting LDL size increased after therapy (+1.4%, P=0.0338), due to a reduction in small, dense LDL-IIIA particles (−25.1%, P=0.0180). Postprandially, rosiglitazone reduced larger HDL-2b (−8.7%, P=0.0056) and increased smaller HDL-3b particles (+12.2%, P=0.0485), with no changes in HDL size. No other effects on lipoproteins size and subclasses were found fasting or post-prandially. By correlation analysis we further found that such changes in lipoproteins size and subclasses were not related to changes in HbA1c or plasma lipids. Conclusions: Rosiglitazone therapy in patients with type-2 diabetes led to anti-atherogenic changes in LDL size and subclasses, with concomitant pro-atherogenic changes in HDL subclasses, despite no effects on plasma lipids and lipoprotein (a). Further studies may evaluate whether these findings affect the clinical endpoints in such patients