Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program.
Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program.
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DOI：
10.2337/db15-1063
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发表时间：
2016-05
期刊：
影响因子：
7.7
通讯作者：
Diabetes Prevention Program Research Group
中科院分区：
文献类型：
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作者：
Walford GA;Ma Y;Clish C;Florez JC;Wang TJ;Gerszten RE;Diabetes Prevention Program Research Group
识别2型糖尿病风险的新生物标志物可能会改善疾病高风险个体的预测和预防，并阐明与糖尿病发展相关的新生物学途径。我们在糖尿病预防计划（DPP）中进行了血浆代谢物分析，这是一项已完成的试验，将高危人群随机分为生活方式、二甲双胍或安慰剂干预组。以前报道的标记物，支链和芳香族氨基酸和谷氨酰胺/谷氨酸，与糖尿病的发生有关（所有P < 0.05），但这些关联在调整临床和生化指标后减弱。相比之下，基线水平的甜菜碱，也被称为甘氨酸甜菜碱（风险比0.84每SD对数代谢物水平，P = 0.02），和其他三种代谢物与事件糖尿病，即使在调整后。此外，甜菜碱增加的生活方式干预，这是最有效的方法来预防糖尿病，增加甜菜碱在2年也与较低的糖尿病发病率（P = 0.01）。我们的研究结果表明，甜菜碱是高风险个体在基线和预防性干预期间糖尿病风险的标志物，它们补充了动物模型，证明甜菜碱在调节代谢健康中的直接作用。
Identifying novel biomarkers of type 2 diabetes risk may improve prediction and prevention among individuals at high risk of the disease and elucidate new biological pathways relevant to diabetes development. We performed plasma metabolite profiling in the Diabetes Prevention Program (DPP), a completed trial that randomized high-risk individuals to lifestyle, metformin, or placebo interventions. Previously reported markers, branched-chain and aromatic amino acids and glutamine/glutamate, were associated with incident diabetes (P < 0.05 for all), but these associations were attenuated upon adjustment for clinical and biochemical measures. By contrast, baseline levels of betaine, also known as glycine betaine (hazard ratio 0.84 per SD log metabolite level, P = 0.02), and three other metabolites were associated with incident diabetes even after adjustment. Moreover, betaine was increased by the lifestyle intervention, which was the most effective approach to preventing diabetes, and increases in betaine at 2 years were also associated with lower diabetes incidence (P = 0.01). Our findings indicate betaine is a marker of diabetes risk among high-risk individuals both at baseline and during preventive interventions and they complement animal models demonstrating a direct role for betaine in modulating metabolic health.