Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program
Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program
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DOI：
10.2337/db19-0236
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发表时间：
2019-12-01
期刊：
影响因子：
7.7
通讯作者：
Gerszten, Robert E.
中科院分区：
文献类型：
--
作者：
Chen, Zsu-Zsu;Liu, Jinxi;Gerszten, Robert E.
2型糖尿病（T2D）的新生物标志物和具有相似临床风险的个体对预防性治疗的反应可能突出在疾病发展中重要的代谢途径。我们分析了来自糖尿病预防计划（DPP）的2，015份基线血浆样本中的331种代谢物。使用考克斯模型确定代谢物与发生的T2 D之间的关联，以及关联是否因治疗组而异（即，生活方式[ILS]，二甲双胍[MET]或安慰剂[PLA]），平均随访3.2年。我们发现69种代谢物与T2D事件相关，无论治疗随机化如何。特别是胞嘧啶是新的，与最低的风险。在一项探索性分析中，35种基线代谢产物与T2D事件的相关性在治疗组间存在差异。根据这些代谢物中的几种（包括特定的磷脂和AMP）的基线水平进行分层，可以改变ILS或MET对糖尿病发展的影响。我们的研究结果强调了糖尿病风险的新标志物和临床高风险个体的预防性治疗效果，并激励进一步研究以验证这些相互作用。
Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.