Association between Advanced Glycation End Products and HDL Dysfunction in Type 2 Diabetes

Abstract

Association between Advanced Glycation End Products and HDL Dysfunction in Type 2 Diabetes The antiatherogenic properties The antiatherogenic properties of HDL include promotion of reverse cholesterol transport, as well as inhibition of oxidation and inflammation. Recent data suggest that HDL is dysfunctional with impaired antioxidative property in diabetes. Since advanced glycation end products (AGEs) have been implicated in oxidative stress, we hypothesize that the increased AGEs in diabetes resulting in enhanced oxidative stress may be associated with HDL dysfunction. We have therefore determined the relationship between serum AGEs and HDL dysfunction in type 2 diabetes. [br]HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation [italic]ex vivo[/italic]. A reference native LDL was incubated with fixed amount of tested HDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid peroxide. The amount of lipid peroxide formed was expressed as arbitrary units of fluorescence intensity (FI). Serum AGEs were assayed by competitive ELISA using a polyclonal rabbit antisera raised against AGE-RNase.[br]Type 2 diabetic patients (n=436) had lower HDL and apolipoprotein AI (apoAI) ([italic]P[/italic][lt]0.001) than age-matched non-diabetic controls (n=182). Serum AGEs were increased in diabetic patients (3.99[plusmn]1.09 units/mL vs. 3.70[plusmn]1.13, [italic]P[/italic]=0.003) whereas the activity of HDL in protecting LDL against oxidation was impaired with more lipid peroxide formed during the incubation (3214[plusmn]685 FI vs. 3088[plusmn]598, [italic]P[/italic]=0.032). HDL dysfunction correlated with serum AGEs in controls (r=0.15, [italic]P[/italic]=0.044) and in type 2 diabetes (r=0.12, [italic]P[/italic]=0.013) whereas the association between HDL dysfunction and HbA1c in diabetic subjects was weaker (r=0.098, [italic]P[/italic]=0.042). HDL dysfunction was not associated with apoAI or the ratio of apoAI/HDL. [br]In conclusion, the association between serum AGEs and the impaired antioxidative activity of HDL suggests that HDL dysfunction in diabetes may be partly due to the increased oxidative stress induced by AGEs. Whether the reduced antioxidative activity of HDL is due to consumption of HDL associated antioxidative enzymes and the roles of AGEs involved are under investigation. HUALI ZHOU, SAMMY W. M. SHIU, YING WONG, KATHRYN C. B. TAN. 868-P Hong Kong, China. Diabetic Dyslipidemia