Efficacy of oral rosuvastatin intervention on HDL and its associated proteins in men with type 2 diabetes mellitus

Abstract

Purpose: High-density lipoprotein (HDL) undergoes structural and functional modification in patients with type 2 diabetes mellitus (T2DM). There are limited data on effect of rosuvastatin on HDL-associated proteins and the antiatherogenic effects of rosuvastatin. The present study intended to study the efficacy of rosuvastatin intervention on HDL-associated proteins and its other antiatherogenic effects in men with T2DM.

Methods: Men with T2DM on oral antidiabetic treatment, with LDL-C levels > 75 mg/dL and willing for rosuvastatin intervention (20 mg/day orally for a period of 12 weeks), were included. Fasting glucose, lipid profile were measured using standard methods. Oxidized low-density lipoprotein (oxLDL), oxidized HDL (oxHDL), paraoxonase-1 (PON-1), tumour necrosis factor-α (TNF-α) and lecithin:cholesterol acyltransferase (LCAT) in serum were measured by ELISA; serum myeloperoxidase (MPO) by spectrophotometric method and cholesterol efflux by fluorometric assay. Carotid intima-media thickness (cIMT) measurement to assess vascular health status was done using doppler.

Results: Rosuvastatin produced a significant decrease (p < 0.05) in lipids (total cholesterol, triglycerides, LDL-C); oxidative stress (oxLDL, oxHDL, MPO); inflammation (TNF-α); LCAT concentration; cIMT; significant increase in antiatherogenic HDL and cholesterol efflux (p < 0.05) and no change in apoA-I levels from baseline to 12 weeks of follow-up. A decrease in MPO activity was found to be independently associated with an increase in cholesterol efflux.

Conclusions: Post intervention there is a quantitative and qualitative improvement in HDL, which helps in its reverse cholesterol transport (RCT) and antioxidant functions. Improvement in HDL functions and suppression of inflammation by rosuvastatin lead to regression in cIMT, which is beneficial in decreasing the progression of cardiovascular disease (CVD) in men with diabetes.

Keywords: Cholesterol efflux; High-density lipoprotein function; Myeloperoxidase; Oxidized high-density lipoprotein; Oxidized low density lipoprotein; Type 2 diabetes mellitus.