The Beneficial Effects of Alpha Lipoic Acid Supplementation on Lp-PLA2 Mass and Its Distribution between HDL and apoB-Containing Lipoproteins in Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Nima Baziar,Mehdi Hedayati,Najva Ahmaripour,Mahshid Abd Mishani,Saeed Hosseini,Kurosh Djafarian,Zeinab Faghfoori,Ensieh Nasli-Esfahani,Mostafa Qorbani

doi:10.1155/2020/5850865

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a new specific vascular inflammation biomarker that is carried by the lipoproteins in the blood and plays a prominent role in the pathogenesis of atherosclerosis. Increased Lp-PLA2 levels and impaired Lp-PLA2 distribution across high-density lipoprotein (HDL) and non-HDL lipoproteins have been reported in diabetic patients, which is associated with the increase in cardiovascular disease (CVD) risk. This study is aimed at investigating the effect of alpha lipoic acid (ALA), as an antioxidant with potential cardioprotective properties, on the Lp-PLA2 mass and its distribution in diabetic patients. In a double-blind, randomized, placebo-controlled clinical trial, seventy diabetic patients were randomly allocated to ALA (1200 mg ALA as two 600 mg capsules/day) and placebo (two maltodextrin capsules/day) groups. The serum levels of total Lp-PLA2 mass, HDL-Lp-PLA2, oxidized low-density lipoproteins (ox-LDL), apolipoprotein A1 (apo A1), lipid profiles, fasting blood sugar (FBS), and insulin were measured, and apolipoprotein B- (apoB-) associated Lp-PLA2 and homeostasis model of assessment index (HOMA-IR) were calculated at the baseline and after 8 weeks of intervention. ALA significantly decreased the ox-LDL, total Lp-PLA2 mass, apoB-associated Lp-PLA2, and percent of apoB-associated Lp-PLA2 and triglyceride and increased the percent of HDL-Lp-PLA2 compared with the placebo group but had no significant effect on HDL-Lp-PLA2 mass, apo A1, lipid profiles, and glycemic indices. There was a positive correlation between the reduction in the ox-LDL level and total Lp-PLA2 mass in the ALA group. In conclusion, ALA may decrease the CVD risk by reducing the ox-LDL and Lp-PLA2 mass and improving the Lp-PLA2 distribution among lipoproteins in type 2 diabetic patients.

Highlights

Type 2 diabetic (T2D) patients present a high prevalence of cardiovascular events with or without established cardiovascular diseases (CVDs) [1]
There were no significant differences in terms of HOMA-IR, fasting serum glucose, insulin, total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) before and after the intervention in both groups
At the baseline of the study, we found a positive correlation between total lipoproteinassociated phospholipase A2 (Lp-PLA2) mass with TC (r = 0:355, P = 0:003), LDL (r = 0:279, P = 0:019), and oxidized low-density lipoproteins (ox-LDL) (r = 0:762, P < 0:001)

Summary

Introduction

Type 2 diabetic (T2D) patients present a high prevalence of cardiovascular events with or without established cardiovascular diseases (CVDs) [1]. According to Adult Treatment Panel-III (ATP-III) guidelines, measuring the Lp-PLA2 levels is useful for a more accurate diagnosis of coronary heart disease (CHD) risk [5], especially in patients with low-density lipoprotein (LDL) less than 130 mg/dl [6]. Lp-PLA2 may have a role in the pathogenesis of atherosclerosis This enzyme breakdowns phospholipids in oxidized low-density lipoproteins (ox-LDL) into two proinflammatory and proatherogenic products, lysophosphatidylcholine and oxidized free fatty acids, these inflammatory factors promote atherosclerosis [7,8,9]. It has been proposed that Lp-PLA2 mediates ox-LDL-induced inflammatory responses in the atherosclerotic plaque and is a predictor of coronary events independent of traditional risk factors [4, 8, 10]. Based on several genome-wide association studies (GWAS), the causal relation between Lp-PLA2 and CHD remains controversial [11,12,13]

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