Berg T J, Snorgaard O, Faber J, Torjesen P A, Hildebrandt P, Mehlsen J, Hanssen K F
Department of Endocrinology, Aker University Hospital, Oslo, Norway.
Diabetes Care. 1999 Jul;22(7):1186-90. doi: 10.2337/diacare.22.7.1186.
Impairment of left ventricular diastolic function, possibly caused by increased collagen cross-linking of the cardiac muscle, is common in patients with type 1 diabetes even without coronary artery disease. Advanced glycation end products (AGEs) cross-link tissue collagen and are found within myocardial fibers. The aim of this study was to examine for a possible association between circulating AGEs and left ventricular cardiac function.
Left ventricular diastolic and systolic function were assessed by M-mode and Doppler echocardiography in 52 patients with type 1 diabetes, age 40 +/- 13 (mean +/- SD) years, diabetes duration 17 +/- 13 years, and HbA1c 8.3 +/- 1.1%. Serum levels of AGEs and N epsilon-(carboxymethyl)lysine (CML) were measured by newly developed competitive immunoassays.
A positive correlation was found between serum levels of AGEs and isovolumetric relaxation time (IVRT), r = 0.46 (P < 0.0008), and left ventricular diameter during diastole, r = 0.37 (P < 0.008). The systolic parameters did not correlate with serum levels of AGEs. Stepwise regression analysis showed that 21% of the IVRT variation could be explained by serum levels of AGEs (F = 11.4, P < 0.002), whereas serum levels of CML, HbA1c, albumin excretion rate, diabetes duration, and mean arterial blood pressure were of no importance. AGE levels were significantly increased in men compared with women (P < 0.03) and present or former smokers (P < 0.04).
Increased serum levels of AGEs, unlike serum levels of CML, are associated with heart stiffness in patients with type 1 diabetes, possibly mediated by the cross-linking properties of AGEs.
1型糖尿病患者即使没有冠状动脉疾病，也常出现左心室舒张功能受损，这可能是由于心肌胶原交联增加所致。晚期糖基化终产物（AGEs）可使组织胶原交联，并存在于心肌纤维内。本研究旨在探讨循环中AGEs与左心室心功能之间是否存在可能的关联。
采用M型和多普勒超声心动图对52例1型糖尿病患者的左心室舒张和收缩功能进行评估，患者年龄40±13（平均±标准差）岁，糖尿病病程17±13年，糖化血红蛋白（HbA1c）为8.3±1.1%。采用新开发的竞争性免疫分析法测定血清AGEs和N-ε-（羧甲基）赖氨酸（CML）水平。
血清AGEs水平与等容舒张时间（IVRT）呈正相关，r = 0.46（P < 0.0008），与舒张期左心室直径呈正相关，r = 0.37（P < 0.008）。收缩参数与血清AGEs水平无相关性。逐步回归分析显示，IVRT变化的21%可由血清AGEs水平解释（F = 11.4，P < 0.002），而血清CML水平、HbA1c、白蛋白排泄率（AER）、糖尿病病程和平均动脉血压（MAP）则无影响。男性的AGE水平显著高于女性（P < 0.03），吸烟者（包括现吸烟者和既往吸烟者）的AGE水平显著高于非吸烟者（P < 0.04）。
与血清CML水平不同，1型糖尿病患者血清AGEs水平升高与心脏僵硬度相关，可能是由AGEs的交联特性介导的。
