OBJECTIVE The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.

RESEARCH DESIGN AND METHODS Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271).

RESULTS Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A_1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28–0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event (P = 0.002).

CONCLUSIONS Lower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.

目的本研究的目的是确定晚期糖基化终产物（AGE）和氧化产物（OP）的血浆水平是否可预测2型糖尿病的心血管疾病（CVD）发生率。

研究设计与方法在两个高强度葡萄糖溶液中，基线时分别测定了五种特定的年龄（甲基乙二醛氢咪唑酮，羧甲基赖氨酸，羧乙基赖氨酸，3-脱氧葡萄糖酮氢咪唑酮和乙二醛氢咪唑酮）和两个OP（2-氨基己二酸和甲硫氨酸亚砜[MetSO]）。降低研究：1）退伍军人事务糖尿病试验（VADT）的一个亚组（n = 445）和2）从糖尿病控制心血管风险的行动（ACCORD）研究中嵌套的病例对照亚组（n = 271）。

结果几种AGE和OP的水平升高与年龄增长，肾脏功能下降，先前的CVD和更长的糖尿病持续时间有关，但与血红蛋白A _1c无关。在VADT中，在调整了年龄，种族/民族，性​​别，以前的CVD事件，肾脏功能，治疗分配和糖尿病持续时间（风险比[HR]）后，发生CVD事件的风险增加（n = 107）与较低的MetSO相关。 0.53； 95％CI为0.28-0.99；P = 0.047）。低MetSO和高3-脱氧葡糖酮氢咪唑酮浓度的个体发生CVD的风险最高（HR 1.70；P = 0.01）。在ACCORD研究中，发生CVD事件的患者（n = 136）的MetSO较低（降低14％；P= 0.007）和更高的乙二醛氢咪唑酮和羧甲基赖氨酸（分别为18％和15％；两者均为P = 0.04）；但是，在针对先前的CVD事件进行调整后，只有MetSO的差异仍然显着（P = 0.002）。

结论较低的MetSO水平和较高的选择AGE水平与心血管事件增加有关，可能有助于解释强化降糖在2型糖尿病中的作用。