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组织金属蛋白酶抑制剂1与中国人群2型糖尿病风险

Tissue inhibitor matrix metalloproteinase 1 and risk of type 2 diabetes in a Chinese population.

作者信息

Wang Yeli, Yuan Jian-Min, Pan An, Koh Woon-Puay

机构信息

Health Services and Systems Research, Duke-NUS Medical School, Singapore.

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

出版信息

BMJ Open Diabetes Res Care. 2020 Apr;8(1). doi: 10.1136/bmjdrc-2019-001051.

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.

摘要

引言

无创性增强肝纤维化(ELF)评分由基质金属蛋白酶-1组织抑制剂(TIMP1)、透明质酸(HA)和III型前胶原氨基端前肽(PIIINP)组成,已被证明能准确预测非酒精性脂肪性肝病(NAFLD)患者的纤维化阶段。然而,尚无研究探讨ELF评分或其组成部分是否也能预测2型糖尿病,2型糖尿病通常与NAFLD共存且具有相同的致病异常。因此,我们首次前瞻性地研究了它们与2型糖尿病风险的关联。

研究设计与方法

在新加坡华人健康前瞻性研究中,对254例2型糖尿病患者和254例年龄及性别匹配的对照者进行了ELF评分测定。病例在采血时(1999 - 2004年)血红蛋白A1c(HbA1c)水平<6.5%,并在随访II期(2006 - 2010年)报告患有糖尿病。对照者在采血时HbA1c水平<6.0%,且在随访II期未患糖尿病。采用多变量条件逻辑回归模型评估ELF与糖尿病的关联。

结果

较高的TIMP1水平与2型糖尿病风险增加相关,最高四分位数与最低四分位数相比的比值比为2.56(95%可信区间1.23至5.34;p趋势 = 0.035)。然而,ELF评分、PIIINP和HA与2型糖尿病风险无显著关联。

结论

较高的TIMP1水平而非ELF评分、PIIIMP和HA与中国成年人2型糖尿病风险增加相关。我们的结果表明,TIMP1水平升高可能通过肝纤维化以外其他途径促成2型糖尿病的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e1/7199153/7a8256fc5725/bmjdrc-2019-001051f01.jpg

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