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Association Between Homocysteine and Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis

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Abstract

Background

Several studies have been performed to assess the relationship between hyperhomocysteinemia and type 2 diabetes mellitus (T2DM). However, inconsistent results have been obtained. Therefore, we performed this meta-analysis to address this knowledge gap.

Methods

We searched PubMed, Cochrane library, and EMBASE database for studies that evaluated the relationship between blood homocysteine (HCY) level and T2DM from inception to Jun 2019. The quality of all included studies was assessed by the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research Quality (AHRQ). RevMan5.3 and Stata12.0 were used for data analyses.

Results

Twenty-five studies (including 1881 cases and 2868 controls) on blood HCY level in T2DM were pooled in our meta-analysis. The blood HCY level in the T2DM patients was significantly higher than in the healthy individuals (SMD = 0.63, 95% CI = 0.43–0.84, and p < 0.001, I2 = 89%, p < 0.001), ignores the effects of age, sex, cardiovascular and cerebrovascular disease conditions, and other comorbidity. Additionally, in T2DM patients with nephropathy or retinopathy, blood HCY level was also significantly higher than in those with only T2DM (SMD = 1.17, 95% CI = 0.76–1.58, p < 0.001; I2 = 90%, p < 0.001 and SMD = 0.91, 95% CI = 0.39–1.44, p <0.001; I2 = 82%, p <0.001, respectively).

Conclusion

Our meta-analysis revealed the HCY level in the blood of T2DM patients was significantly higher than those of the health subjects, especially in patients with diabetic nephropathy (DN) and diabetic retinopathy (DR).

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Funding

This study was supported by the National Natural Science Foundation of China (Grants No: 81760108, No: 81560099, and No: 81660545); the Applied Basic Research Key Projects of Yunnan Province (Grant No: 2018FA039); Yunnan Provincial Fund Project (Grant No: 2016ZZX096), and the Joint Special Fund Project of Applied Basic Research of Kunming Medical University, Department of Science and Technology of Yunnan Province (Grant No: 2017FE468 (-013)).

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Author notes

  1. Jin-Xiang Wang and Ding-Yun You contributed equally to this work.

Authors and Affiliations

  1. Department of Digestive Medicine, The First Affiliated Hospital, Kunming Medical University, 295 Xichang Rd, Kunming, 650032, Yunnan, China

    Jin-Xiang Wang, Dan Zhang, Ming-Ke Li, Chun-Mei Li, Jun-Yan Lv, Su-Feng Luo & Lan-Qing Ma

  2. Department of Public Health, Kunming Medical University, Kunming, 650500, Yunnan, China

    Ding-Yun You & Yan-Hong Yang

  3. University Library, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China

    Hua-Ping Wang & Rui Liao

  4. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, 650500, Yunnan, China

    Cheng-Gang Zou

  5. Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, 100730, China

    Xue Yu

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  1. Jin-Xiang Wang
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Contributions

Jin-Xiang Wang and Rui Liao designed the study, conducted the literature search and screening, as well the data extraction and analyses. Jin-Xiang Wang wrote the first draft of the manuscript. Ding-Yun You analyzed the statistical data. All the authors revised the subsequent drafts for important intellectual content, read, and approved the final version of the manuscript.

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Correspondence to Xue Yu, Rui Liao or Lan-Qing Ma.

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ESM 1

Fig. A1 Forest plot for HCY level in T2DM patients VS controls stratified by BMI. Fig. A2 Forest plot for HCY levels in T2DM patients VS controls stratified by ethnicity. Fig. A3 Begg’s funnel plot of the included studies. (DOCX 218 kb)

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Wang, JX., You, DY., Wang, HP. et al. Association Between Homocysteine and Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis. Int J Diabetes Dev Ctries 41, 553–562 (2021). https://doi.org/10.1007/s13410-021-00933-9

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