engleski

Novel basic science of diabetic complications- Decreased level of endogenous secretory receptor for advanced glycation endproducts in diabetes with concomitant dyslipidemia.

Aim Diabetes is a major independent risk factor for vascular disease. Advanced glycation endproducts (AGE) and their receptor (RAGE) are implicated in the pathogenesis of diabetic complications and atherosclerosis. We have investigated endogenous secretory receptor, the soluble form of RAGE, in diabetes with or without concomitant hyperlipemia to assess a possible association among parameters of the AGE/esRAGE axis and macrovascular outcomes. An attempt was also made to establish whether antidiabetic therapy with (or without) lipid lowering treatment could have a metabolic effect on the esRAGE expression. Methods Methylglyoxal-adducts, total AGEs and esRAGE were measured in 168 subjects with either type 2 diabetes (n=32), dyslipidemia with normal glucose metabolism (n=38) or diabetes with dyslipidemia (n=98). A history of macrovascular events (cardiovascular disease, cerebral vasculopathy or peripheral vascular disease) was recorded in 72 subjects. Results esRAGE levels were significantly lower (p=0.004) in diabetic patients with dyslipidemia in comparison with hyperlipemia or diabetes alone (306 (264-348) vs 367 (319-414) and 404 (356-451) pg/ml, respectively). Furthermore, suppressed esRAGE expression was observed in the groups with the history of higher incidence of vascular events. Multiple regression analyses revealed that HDL- cholesterol (β=0.47), excretion of MG- adducts (β=0.46), HbA1c (β=0.51) and Lp(a) (β=0.33) were independent determinants of esRAGE (p<0.000) level. A pronounced esRAGE-increasing effect of statins was not observed by fibrate treatment (386±144 vs 316±111 pg/ml, p=0.034). A combination insulin and oral hypoglycemic (OHA) therapy induced esRAGE expression in comparison with insulin or OHA alone (470 to 409 and 342 pg/ml, respectively). Conclusion Decreased expression of esRAGE was found in diabetes with concomitant dyslipidemia, independent of the AGE levels. Significant therapy-induced increase in esRAGE expression and its positive correlation with HDL- cholesterol might be associated with its possible antiatherogenic effects, probably acting as a decoy for various AGE-ligands.

Diabetes; advanced glycation endproducts; endogenous secretory recepotor for AGE

nije evidentirano