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Healthy lifestyle, plasma metabolites, and risk of cardiovascular disease among individuals with diabetes

  • Qi Lu
    Affiliations
    Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Junxiang Chen
    Affiliations
    Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Rui Li
    Affiliations
    Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yi Wang
    Affiliations
    Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Zhouzheng Tu
    Affiliations
    Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Tingting Geng
    Affiliations
    Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Liegang Liu
    Affiliations
    Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally as corresponding authors.
    An Pan
    Correspondence
    Corresponding author.
    Footnotes
    1 These authors contributed equally as corresponding authors.
    Affiliations
    Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally as corresponding authors.
    Gang Liu
    Correspondence
    Corresponding author.
    Footnotes
    1 These authors contributed equally as corresponding authors.
    Affiliations
    Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally as corresponding authors.

      Highlights

      • Healthy lifestyle is associated with cardiovascular disease (CVD) risk among diabetic subjects.
      • Adherence to multiple healthy lifestyle factors was associated with improved nuclear magnetic resonance (NMR) metabolites from different pathways.
      • Fatty acids showed mediating effects in the association of multiple lifestyle factors with CVD risk.
      • Targeting shared mediators may facilitate effective CVD prevention strategies among people with diabetes.

      Abstract

      Background and aims

      Lifestyle management is a fundamental aspect of diabetes care to prevent cardiovascular disease (CVD); however, the underlying metabolic mechanism is not well established. We aimed to identify metabolites associated with different lifestyle factors, and estimate their mediating roles between lifestyle and CVD risk among people with diabetes.

      Methods

      Lifestyle and metabolomic data were available for 5072 participants with diabetes who were free of CVD at baseline in the UK Biobank. The healthy level of 5 lifestyle factors was defined as non-central obesity, non-current smoking, moderate alcohol intake, physically active, and healthy diet. A total of 44 biomarkers across 7 metabolic pathways including lipoprotein particles, fatty acids, amino acids, fluid balance, inflammation, ketone bodies, and glycolysis were quantified by nuclear magnetic resonance (NMR) spectroscopy.

      Results

      All 44 assayed metabolites were significantly associated with at least one lifestyle factor. Approximately half of metabolites, which were mostly lipoprotein particles and fatty acids, showed a mediating effect between at least one lifestyle factor and CVD risk. NMR metabolites jointly mediated 43.4%, 30.0%, 16.8%, 43.4%, and 65.5% of the association of non-central obesity, non-current smoking, moderate alcohol intake, physically active, and healthy diet with lower CVD risk, respectively. In general, though metabolites that significantly associated with lifestyle were mostly different across the 5 lifestyle factors, the pattern of association was consistent between fatty acids and all 5 lifestyle factors. Further, fatty acids showed significant mediating effects in the association between all 5 lifestyle factors and CVD risk with mediation proportion ranging from 12.2% to 26.8%.

      Conclusions

      There were large-scale differences in circulating NMR metabolites between individuals with diabetes who adhered to a healthy lifestyle and those did not. Differences in metabolites, especial fatty acids, could partially explain the association between adherence to multiple healthy lifestyle and lower CVD risk among people with diabetes.

      Graphical abstract

      Keywords

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