engleski

Autoantibodies against oxidized LDL and advanced glycation endproducts in NIDDM with nephropathy

Oxidized LDL (oxLDL) plays an important role in the development of atherosclerosis. There is also evidence that advanced glycation endproducts (AGEs) are implicated in the pathogenesis of diabetic vascular complications. The aim of this study was to investigate the biological marker of in vivo LDL oxidation (autoantibodies against oxLDL) and serum AGE level in two age-matched groups of NIDDM patients (65 without microangiopathy and 27 with nephropathy), and in 25 normolipemic controls. Nephropathy was assessed on the basis of complete clinical examination. There was no difference in the glycemic control (HbA1c 7.9ą2.5 vs 8.3ą2.0), age (59.8ą12 vs 61.1ą9), diabetes duration (8.9ą5.1 vs 9.9ą4.9) and lipoprotein status (CH:6.2ą1.3 vs 6.8ą1.2, LDL-c:4.2ą1.1 vs 4.3ą0.9 ; TG:2.1ą1.3 vs 2.6ą1.7) between the two NIDDM groups. Serum IgG antibodies against oxLDL were determined by ELISA using malondialdehyde-derived LDL (MDA-LDL) as antigen. Competitive ELISA using polyclonal anti-AGE antibodies was used to measure AGEs. The titer of autoantibodies against MDA-LDL was higher in both NIDDM groups vs controls (32.2ą5.5 vs 20.1ą4.8 AcU/ml, p<0.001). NIDDM patients with nephropathy showed higher oxLDLab titer than those free from microangiopathy (34.8ą8.6 vs 28.1ą7.3 ; p<0.05). A significant positive correlation was found between oxLDLab and urinary albumin/creatinine ratio (r=0.46, p<0.05). However, there was no correlation of oxLDLab with either standard lipid parameters or diabetes duration. OxLDLab was by 20% higher in NIDDM patients with coronary heart disease (n=5) than in NIDDM patients with nephropathy. A negative correlation was found between oxLDLab titer and metabolic control in both NIDDM groups (oxLDLab vs HbA1c, AGEs ; r= -0.25, r= -3.3 ; p<0.001). Serum AGEs were significantly higher in NIDDM patients with nephropathy than in those free from microangiopathy (54.1ą13 vs 47.1ą14, p<0.05). A significant correlation was recorded between the parameters of early and advanced glycation (HbA1c vs AGEs p<0.0001). In conclusion, the results indicated the processes of oxidation and glycation to be more pronounced in nephropathy in vivo than in the age-matched NIDDM free from nephropathy, possibly contributing to the former group's susceptibility to accelerated vascular lesions.

diabetes; oxidised-LDL; glycation

nije evidentirano