Luft V C, Duncan B B, Schmidt M I, Chambless L E, Pankow J S, Hoogeveen R C, Couper D J, Heiss G
Graduate Studies Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Food and Nutrition Research Centre, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Diabet Med. 2016 Oct;33(10):1392-8. doi: 10.1111/dme.12963. Epub 2015 Oct 6.
To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults.
Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design.
In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99).
Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes.
验证循环中羧甲基赖氨酸（CML，一种晚期糖基化终产物）的空腹水平升高是否可预测中年成年人患糖尿病的风险。
采用分层病例队列设计，在社区动脉粥样硬化风险研究中，我们对543名患糖尿病的中年个体和514名未患糖尿病的中年个体进行了为期9年的随访。采用加权Cox比例风险分析来考虑该设计。
在加权分析中，CML水平与人体测量、炎症或代谢变量之间的相关性极小（Pearson相关系数通常<0.10）。将CML作为连续变量进行建模，并对年龄、性别、种族、中心、糖尿病家族史、BMI、腰臀比、非酯化脂肪酸、氧化型低密度脂蛋白胆固醇、肾小球滤过率、吸烟、炎症评分、脂联素、瘦素、胰岛素和血糖水平进行调整后，CML与糖尿病风险增加相关[风险比（HR）=1.35；95%置信区间（CI）为1.09 - 1.67，CML每增加100 ng/ml]。基线血糖水平和种族各自改变了这种关联（交互作用P<0.05），这种关联仅在空腹血糖受损者（≥5.6 mmol/l，HR = 1.61，95%CI 1.26 - 2.05）和白人参与者中存在（HR = 1.50，95%CI 1.13 - 1.99）。
在对糖尿病的多种风险因素进行调整后，空腹CML水平升高可预测新发糖尿病的发生，这种关联在空腹血糖受损者和白人参与者中存在。这些前瞻性研究结果表明，晚期糖基化终产物可能在糖尿病的发生中起作用。
