Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus

Abstract

Objective: To investigate whether apolipoprotein A (apoA)-I glycation and paraoxonase (PON) activities are associated with the severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Methods: Relative intensity of apoA-I glycation and activities of high-density lipoprotein (HDL)-associated PON1 and PON3 were determined in 205 consecutive T2DM patients with stable angina with (n=144) or without (n=61) significant CAD (luminal diameter stenosis≥70 %). The severity of CAD was expressed by number of diseased coronary arteries, extent index, and cumulative coronary stenosis score (CCSS). Results: The relative intensity of apoA-I glycation was higher but the activities of HDL-associated PON1 and PON3 were lower in diabetic patients with significant CAD than in those without. The relative intensity of apoA-I glycation increased but the activities of HDL-associated PON1 and PON3 decreased stepwise from 1 - to 3 - vessel disease patients (P for trend<0.001). After adjusting for possible confounding variables, the relative intensity of apoA-I glycation correlated positively, while the activities of HDL-associated PON1 and PON3 negatively, with extent index and CCSS, respectively. At high level of apoA-I glycation (8.70~12.50 %), low tertile of HDL-associated PON1 (7.03~38.97U/mL) and PON3 activities (7.11~22.30U/mL) was associated with a 1.97- and 2.49- fold increase of extent index and 1.73- and 2.68- fold increase of CCSS compared with high tertile of HDL-associated PON1 (57.85~154.82U/mL) and PON3 activities (39.63~124.10U/mL), respectively (all P<0.01). Conclusions: Elevated apoA-I glycation and decreased activities of HDL-associated PON1 and PON3, and their interaction are associated with the presence and severity of CAD in patients with T2DM.