Abstract
BACKGROUND: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. METHODS: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. RESULTS: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10-1.64) and 1.99 (1.55-2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10-1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06-1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). CONCLUSIONS: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry.