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Relationship between plasma growth differentiation factor 15 levels and complications of type 2 diabetes mellitus: a cross-sectional study

  • Author Footnotes
    # These authors contributed equally to this article.
    Xiaoyan Zhu
    Footnotes
    # These authors contributed equally to this article.
    Affiliations
    Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, 215004, China

    Institute of Suzhou Biobank, Suzhou, Jiangsu, 215004, China

    School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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  • Author Footnotes
    # These authors contributed equally to this article.
    Yue Zhang
    Footnotes
    # These authors contributed equally to this article.
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Author Footnotes
    # These authors contributed equally to this article.
    Fei Liang
    Footnotes
    # These authors contributed equally to this article.
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Jieyun Yin
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Lai Jiang
    Affiliations
    Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, 215004, China

    Institute of Suzhou Biobank, Suzhou, Jiangsu, 215004, China
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  • Wenyan Cai
    Affiliations
    The Affiliated Suzhou Hospital of Nanjing Medical University, Jiangsu, 215000, China
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  • Jianan Lu
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Chen Zhang
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Yue Xiao
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Haoyue Teng
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Wenxin Ge
    Affiliations
    Department Of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
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  • Yihe Hu
    Affiliations
    Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, 215004, China
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  • Yan Lu
    Affiliations
    Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, 215004, China
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  • Jian Su
    Affiliations
    Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, 210009, China
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  • Jun Zhang
    Correspondence
    Correspondence to: Jun Zhang, MD, Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, China 215004. Tel/fax: +86 0512 68633786 /
    Affiliations
    Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu, 215004, China
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  • Ming Wu
    Correspondence
    Correspondence to: Ming Wu, PhD, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China 210009. Tel/fax: +86 025 83759981 /
    Affiliations
    Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, 210009, China
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  • Author Footnotes
    # These authors contributed equally to this article.
Published:September 13, 2022DOI:https://doi.org/10.1016/j.jcjd.2022.09.116
Relationship between plasma growth differentiation factor 15 levels and complications of type 2 diabetes mellitus: a cross-sectional study
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      Abstract

      Objective

      To investigate the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in Chinese community-based population.

      Methods

      Based on a cross-sectional study registered in National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and further tested for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular complications [diabetic kidney disease (DKD), diabetic retinopathy and neuropathy] were evaluated. Logistic regressions were conducted to explore the associations of GDF15 with risk of diabetic complications, while linear regressions were used to assess the relationship of GDF15 with other clinical features.

      Results

      Overall, 459 (27.18%) of T2DM patients had complications. GDF15 levels were significantly higher in patients with any type of complication compared to their counterparts. With each SD increase of base 10 logarithms of GDF15 (lg-GDF15), risks of overall complications elevated to 1.17 times [95% confidence interval (95%CI)=1.03-1.32]. In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger [adjusted odds ratio (OR) (95%CI)=1.24 (1.08-1.43)], especially for DKD [adjusted OR (95%CI)=1.51 (1.19-1.93)]. Subgroup analyses showed that association strength between GDF15 and complications varied in distinct age and T2DM duration subgroups. Besides, patients with two or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices.

      Conclusion

      Our study showed that higher GDF15 levels were associated with T2DM complications, especially DKD.

      Keywords

      Abbreviations:

      T2DM (type 2 diabetes mellitus), GDF15 (growth differentiation factor-15), SD (standard deviation), OR (odds ratio), 95%CI (95% confidence interval), IDF (International Diabetes Federation), MIC-1 (macrophage inhibitory cytokine), TGF-β (transforming growth factor-β), BMI (body mass index), CVD (cardiovascular disease), DKD (diabetic kidney disease), SBP (systolic blood pressure), DBP (diastolic blood pressure), HbA1c (glycated hemoglobin), GGT (gamma-glutamyl transpeptidase), ALT (alanine transaminase), AST (aspartate aminotransferase), TC (total cholesterol), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol)
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      Article Info

      Publication History

      Accepted: September 3, 2022
      Received in revised form: September 1, 2022
      Received: March 26, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Key Messages:

      1. Higher GDF15 levels were associated with T2DM complications.

      2. Patients with two or more types of complications had higher levels of GDF15 than those with fewer types of complications.

      Author Disclosures: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Funding statement

      This work was supported by the Youth Program of Reinvigorating the Health through Science and Education in Suzhou, China (granted number KJXW2020054), Jiangsu Province Medical Innovation Team Program (K201105), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China, and a Project Funded by Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

      Data availability statement

      The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

      Identification

      DOI: https://doi.org/10.1016/j.jcjd.2022.09.116

      Copyright

      © 2022 Canadian Diabetes Association.

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