Department of Clinical Science,
Department of Heart Disease.
Clin Chem. 2016 May;62(5):755-65. doi: 10.1373/clinchem.2015.250761. Epub 2016 Mar 15.
Several compounds in the choline oxidation pathway are associated with insulin resistance and prevalent diabetes; however, prospective data are scarce.We explored the relationships between systemic and urinary choline-related metabolites and incident type 2 diabetes in an observational prospective study among Norwegian patients.
We explored risk associations by logistic regression among 3621 nondiabetic individuals with suspected stable angina pectoris, of whom 3242 provided urine samples. Reclassification of patients was investigated according to continuous net reclassification improvement (NRI >0).
After median (25th to 75th percentile) follow-up of 7.5 (6.4-8.7) years, 233 patients (6.4%) were registered with incident type 2 diabetes. In models adjusted for age, sex, and fasting status, plasma betaine was inversely related to new-onset disease [odds ratio (OR) per 1 SD, 0.72; 95% CI, 0.62-0.83; P < 0.00001], whereas positive associations were observed for urine betaine (1.25; 1.09-1.43; P = 0.001), dimethylglycine (1.22; 1.06-1.40; P = 0.007), and sarcosine (1.30; 1.13-1.49; P < 0.001). The associations were maintained in a multivariable model adjusting for body mass index, hemoglobin A1c, urine albumin-to-creatinine ratio, estimated glomerular filtration rate, C-reactive protein, HDL cholesterol, and medications. Plasma betaine and urine sarcosine, the indices most strongly related to incident type 2 diabetes, improved reclassification [NRI >0 (95% CI) 0.33 (0.19-0.47) and 0.16 (0.01-0.31), respectively] and showed good within-person reproducibility.
Systemic and urinary concentrations of several choline metabolites were associated with risk of incident type 2 diabetes, and relevant biomarkers may improve risk prediction.
胆碱氧化途径中的几种化合物与胰岛素抵抗和普遍存在的糖尿病有关；然而，前瞻性数据仍然缺乏。我们在一项挪威患者的观察性前瞻性研究中，探讨了系统和尿胆碱相关代谢物与 2 型糖尿病发病之间的关系。
我们通过逻辑回归探讨了 3621 例疑似稳定型心绞痛的非糖尿病个体之间的风险关联，其中 3242 例提供了尿液样本。根据连续净重新分类改善（NRI>0）对患者进行重新分类。
中位（25 至 75 百分位数）随访 7.5（6.4-8.7）年后，233 例患者（6.4%）被确诊患有 2 型糖尿病。在调整年龄、性别和空腹状态的模型中，血浆甜菜碱与新发疾病呈负相关[每 1 SD 的比值比（OR），0.72；95%置信区间，0.62-0.83；P < 0.00001]，而尿液甜菜碱（1.25；1.09-1.43；P = 0.001）、二甲基甘氨酸（1.22；1.06-1.40；P = 0.007）和肌氨酸（1.30；1.13-1.49；P < 0.001）呈正相关。在调整体重指数、糖化血红蛋白、尿白蛋白与肌酐比值、估计肾小球滤过率、C 反应蛋白、高密度脂蛋白胆固醇和药物的多变量模型中，这些关联仍然存在。与 2 型糖尿病发病最相关的血浆甜菜碱和尿液肌氨酸改善了重新分类[NRI >0（95%CI）0.33（0.19-0.47）和 0.16（0.01-0.31）]，并显示出良好的个体内可重复性。
几种胆碱代谢物的系统和尿液浓度与 2 型糖尿病发病风险相关，相关生物标志物可能改善风险预测。
