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Epidemiology/Health Services Research
Tissue inhibitor matrix metalloproteinase 1 and risk of type 2 diabetes in a Chinese population
  1. Yeli Wang1,
  2. Jian-Min Yuan2,3,
  3. An Pan4,
  4. Woon-Puay Koh1,5
  1. 1Health Services and Systems Research, Duke-NUS Medical School, Singapore
  2. 2UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  3. 3Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  4. 4Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  5. 5Saw Swee Hock School of Public Health, National University of Singapore, Singapore
  1. Correspondence to Professor An Pan; panan{at}hust.edu.cn; Professor Woon-Puay Koh; woonpuay.koh{at}duke-nus.edu.sg

Abstract

Introduction The non-invasive enhanced liver fibrosis (ELF) score—comprising tissue inhibitor of matrix metalloproteinases-1 (TIMP1), hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PIIINP)—has been shown to accurately predict fibrosis stages among patients with non-alcoholic fatty liver disease (NAFLD). However, no study has examined whether the ELF score or its components would also be predictive of type 2 diabetes, which commonly coexists and shares the same pathogenic abnormalities with NAFLD. Therefore, we prospectively investigated their associations with type 2 diabetes risks for the first time.

Research design and methods The ELF score was measured among 254 type 2 diabetes cases and 254 age-matched and sex-matched controls nested within the prospective Singapore Chinese Health Study. Cases had hemoglobin A1c (HbA1c) levels <6.5% at blood collection (1999–2004) and reported to have diabetes during follow-up II (2006–2010). Controls had HbA1c levels <6.0% at blood-taking and remained free of diabetes at follow-up II. Multivariable conditional logistic regression models were used to assess the ELF-diabetes association.

Results Higher TIMP1 levels were associated with increased type 2 diabetes risk, and the OR comparing the highest versus lowest quartiles was 2.56 (95% CI 1.23 to 5.34; p trend=0.035). However, ELF score, PIIINP and HA were not significantly associated with type 2 diabetes risks.

Conclusions Higher TIMP1 levels, but not ELF score, PIIIMP and HA, were associated with increased type 2 diabetes risk in Chinese adults. Our results suggested that elevated TIMP1 levels may contribute to the type 2 diabetes development through pathways other than liver fibrosis.

  • epidemiology
  • type 2 diabetes
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-001051

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    Footnotes

    • AP and W-PK are joint senior authors.

    • Contributors AP and W-PK conceived the study, interpreted the data and critically revised the reports. YW did the search, analyzed and interpreted the data, drafted and critically revised the reports. J-MY contributed to the acquisition of study materials and critically revised the reports. All authors revised and approved the final report.

    • Funding This work was supported by the National Medical Research Council, Singapore (NMRC/CIRG/1354/2013) and National Institutes of Health, USA (RO1 CA144034 and UM1 CA182876). AP is supported by the National Key Research and Development Program of China (2017YFC0907504).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study protocol was approved by the Institutional Review Boards at the National University of Singapore and the University of Pittsburgh (NUS-IRB Ref Code: 06–027).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request from corresponding author.