Plasma metabolomics identified novel metabolites associated with risk of type 2 diabetes in two prospective cohorts of Chinese adults.
Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults.



We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts.



We identified four metabolites consistently associated with an increased risk of developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95% confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32-2.42) for alanine, 1.91 (1.41-2.60) for phenylalanine, 1.85 (1.37-2.48) for tyrosine and 1.63 (1.21-2.20) for palmitoylcarnitine (all Ptrend≤ 0.01).



We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D.
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Gaokun
G
Qiu
Department of Nutrition and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Yan
Y
Zheng
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Hao
H
Wang
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Jie
J
Sun
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Hongxia
H
Ma
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Yang
Y
Xiao
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Yizhun
Y
Li
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Yu
Y
Yuan
Department of Cardiovascular Disease, Dongfeng Central Hospital, Hubei University of Medicine, Shiyan, China.
Handong
H
Yang
Department of Cardiovascular Disease, Dongfeng Central Hospital, Hubei University of Medicine, Shiyan, China.
Xiulou
X
Li
Department of Cardiovascular Disease, Dongfeng Central Hospital, Hubei University of Medicine, Shiyan, China.
Xinwen
X
Min
Department of Cardiovascular Disease, Dongfeng Central Hospital, Hubei University of Medicine, Shiyan, China.
Ce
C
Zhang
Department of Cardiovascular Disease, Dongfeng Central Hospital, Hubei University of Medicine, Shiyan, China.
Chengwei
C
Xu
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Yue
Y
Jiang
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Xiaomin
X
Zhang
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Meian
M
He
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
Ming
M
Yang
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Zhibin
Z
Hu
State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China and.|CAS Key Laboratory of Magnetic Resonance in Biological Systems, University of Chinese Academy of Sciences, Wuhan, China.
Huiru
H
Tang
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Hongbing
H
Shen
Department of Nutrition and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Frank B
FB
Hu
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China, wut@mails.tjmu.edu.cn panan@hust.edu.cn.
An
A
Pan
Department of Occupational and Environmental Health and Department of Epidemiology and Biostatistics, Ministry of Education and State Key Laboratory of Environmental Health, Huazhong University of Science and Technology, Wuhan, China, wut@mails.tjmu.edu.cn panan@hust.edu.cn.
Tangchun
T
Wu
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002853:Chromatography, Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010172:Palmitoylcarnitine / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors
D000596:Amino Acids; D015415:Biomarkers; D001786:Blood Glucose; D010172:Palmitoylcarnitine
Chinese population; Type 2 diabetes; nested case-control study; targeted metabolomics