Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes

OBJECTIVE - Impairment of left ventricular diastolic function, possibly cau sed by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanc ed glycation end products (AGEs) cross-link tissue collagen and are found w ithin myocardial fibers. The aim of this study was to examine for a possibl e association between circulating AGEs and left ventricular cardiac functio n. RESEARCH DESIGN AND METHODS - Left ventricular diastolic and systolic funct ion were assessed by M-mode and Doppler echocardiography in 52 patients wit h type 1 diabetes, age 40 +/- 13 (mean +/- SD) years, diabetes duration 17 +/- 13 years, and HbA(1c) 8.3 +/- 1.1%. Serum levels of AGEs and N-epsilon- (carboxymethyl)lysine (CML) were measured by newly developed competitive im munoassays. RESULTS - A positive correlation was found between serum levels of AGEs and isovolumetric relaxation time (IVRT), r = 0.46 (P < 0.0008), and left vent ricular diameter during diastole, r = 0.37 (P < 0.008). The systolic parame ters did not correlate with serum levels of AGEs. Stepwise regression analy sis showed that 21% of the IVRT variation could be explained by serum level s of AGEs (F = 11.4, P < 0.002), whereas serum levels of CML, HbA(1c), albu min excretion rate, diabetes duration, and mean arterial blood pressure wer e of no importance. AGE levels were significantly increased in men compared with women (P < 0.03) and present or former smokers (P < 0.04). CONCLUSIONS - Increased serum levels of AGEs, unlike serum levels of CML, a re associated with heart stiffness in patients with ripe 1 diabetes, possib ly mediated by the cross-linking properties of AGEs.