title: Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study.
abstract: Acylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach.
  
  
  
  A population-based prospective study was conducted among 2,103 community-living Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry.
  
  
  
  Over the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents.
  
  
  
  A panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Pang
authors.initials: P
authors.lastname: Yao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Feijie
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qianlu
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rongxia
authors.initials: R
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Department of Life Sciences and Technology, ShanghaiTech University, Shanghai, China zr@sibs.ac.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China xlin@sibs.ac.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Department of Life Sciences and Technology, ShanghaiTech University, Shanghai, China Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China wujr@sibs.ac.cn.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Wu
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood*; D002681:China; D002853:Chromatography, Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin; D050356:Lipid Metabolism; D016015:Logistic Models; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002331:Carnitine; D006442:Glycated Hemoglobin; D007328:Insulin; C116917:acylcarnitine; C517652:hemoglobin A1c protein, human; C103930:3-dehydrocarnitine