Effects of Rosiglitazone on Fasting and Postprandial Low- and High-Density Lipoproteins Size and Subclasses in Type 2 Diabetes

Abstract

Rosiglitazone may increase cardiovascular risk in patients with type 2 diabetes. Yet, its effects on atherogenic dyslipidemia are still not fully elucidated. In a prospective open-label study rosiglitazone (4 mg/day for 12 weeks) was added to a maximum of 2 oral antidiabetic drugs in 18 diabetic patients. We evaluated the effects on plasma lipids before and after an oral fat load. The size and subclasses of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were also determined (by gradient gel electrophoresis). Rosiglitazone improved glycosylated hemoglobin ([HbA1c] P = .0023), without significant effects on fasting and postprandial plasma lipids. Fasting LDL size increased (+1.4%, P = .034), with less small, dense LDL-IIIA (-25.1%, P = .018). Postprandially, larger HDL-2b reduced (-8.7%, P = .006) and smaller HDL-3b increased (+12.2%, P = .05), without any effects on HDL size. Rosiglitazone led to antiatherogenic changes in LDL size and subclasses, with proatherogenic changes in HDL subclasses, despite no effects on plasma lipids. Their clinical relevance remains to be established.

The effect of weight loss on HDL subfractions and LCAT activity in two genotypes of APOA-II -265T>C polymorphism

“…In another study, it was demonstrated that both HDL2 and HDL3 protect against CVD [41]. However, most studies that investigate the therapeutic modulation of HDL subfraction demonstrate that larger HDL particles are more protective against CVD [42]. In sum, according to a review article by Rizzo et al, further clinical investigations are required to clarify the physicochemical and functional heterogeneity of HDL subfractions [38].…”

The Effect of Intensive Glucose Lowering on Lipoprotein Particle Profiles and Inflammatory Markers in the Veterans Affairs Diabetes Trial (VADT)

“…It is important that changes in LDL2 and LDL4 were also independent of the use of specific classes of glucose-lowering medications, including insulin or rosiglitazone, that previously were shown to increase LDL particle size (18–21,24,28). In contrast with some previous studies (18,19,24), changes in LDL subclasses in our cohort were not related to insulin use.…”

Non-glycemic effects of pioglitazone and incretin-based therapies

“…In addition, a comprehensive review article by Rizos et al has previously shown that thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid, and may also delay the progression of atherosclerosis [7]. However, the effects on the lipid profile significantly differ between the two agents in this class, with pioglitazone overall having more positive effects compared with rosiglitazone; indeed, pioglitazone has been shown to be able to significantly reduce the atherogenicity of lipoproteins, including small, dense low-density lipoproteins (LDL) [8][9][10].…”