Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach.
Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach.
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作者：
Floegel A;Stefan N;Yu Z;Mühlenbruch K;Drogan D;Joost HG;Fritsche A;Häring HU;Hrabě de Angelis M;Peters A;Roden M;Prehn C;Wang-Sattler R;Illig T;Schulze MB;Adamski J;Boeing H;Pischon T
2型糖尿病（T2 D）风险生物标志物的代谢组学发现可能揭示病因学途径，并有助于识别有疾病风险的个体。我们在欧洲癌症与营养前瞻性研究（EPIC）-波茨坦（27，548名成人）中前瞻性研究了通过靶向代谢组学测量的血清代谢物与T2 D风险之间的相关性，包括所有T2 D事件病例（n = 800，平均随访7年）和随机抽取的子队列（n = 2，282）。使用流动注射分析串联质谱法定量基线血清样本中的163种代谢物，包括酰基肉毒碱、氨基酸、己糖和磷脂。血清己糖;苯丙氨酸;二酰基磷脂酰胆碱C32：1、C36：1、C38：3和C40：5与T2 D和血清甘氨酸风险增加独立相关;鞘磷脂C16：1;酰基烷基磷脂酰胆碱C34：3、C40：6、C42：5、C44：4和C44：5;溶血磷脂酰胆碱C18：2与风险降低相关。代谢物的差异在很大程度上由两个具有相反风险关联的代谢物因素解释（极端五分位数中的因素1相对风险为0.31 [95% CI 0.21-0.44]，因素2为3.82 [2.64-5.52]）。与已确定的风险因素相比，代谢物显著改善了T2 D预测。在Tübingen家族研究中，它们进一步与胰岛素敏感性和分泌相关，并在独立KORA（奥格斯堡地区合作健康研究）队列中部分重复。这些数据表明，代谢改变，包括糖代谢物，氨基酸和含胆碱的磷脂，与早期T2 D的风险较高有关。
Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.
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影响因子：
4.8
作者：
Jacobs, RL;Devlin, C;Vance, DE
通讯作者：
Vance, DE
影响因子：
16.2
作者：
Ford, Earl S.;Schulze, Matthias B.;Boeing, Heiner
通讯作者：
Boeing, Heiner
DOI：
10.1016/s0197-2456(00)00104-5
发表时间：
2000-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Hsieh, FY;Lavori, PW
通讯作者：
Lavori, PW
影响因子：
105.7
作者：
Higgins, JPT;Thompson, SG;Altman, DG
通讯作者：
Altman, DG
影响因子：
3.9
作者：
Bergmann, MM;Bussas, U;Boeing, H
通讯作者：
Boeing, H