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Association of SIRT6 circulating levels with urinary and glycometabolic markers in pre-diabetes and diabetes

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Abstract

Aim

The study is aimed to detect the expression of serum Sirtuin 6 (SIRT6) with different severities and urinary albumin creatinine ratios (UACR) in type 2 diabetes mellitus (T2DM) patients, thus exploring the association of SIRT6 together with glycolipid metabolism and urinary protein in the cross-sectional study.

Methods

T2DM patients (313 cases), pre-diabetic patients (102 cases), and healthy volunteers (100 cases) were selected. T2DM patients were divided into the normal albuminuria (103 cases, UACR < 30 mg/g), micro-albuminuria (106 cases, UACR 30–300 mg/g), and large amount of albuminuria group (104 cases, UACR > 300 mg/g) based on different UACR levels. The medical history was asked, biochemical indicators were detected, hematuria samples were taken, serum SIRT6 levels were detected, and detailed statistical analysis was conducted.

Results

FPG, 2 h-PG, HOMA-IR, HbA1c, and LDL-C increased, while ISI and HDL-C decreased with the aggravation of diabetic status (P < 0.05). HbA1c, UACR, TNFα, HIF1α, and SIRT6 increased with UACR in T2DM patients (P < 0.05). Correlation analysis demonstrated that SIRT6 was significantly positively correlated with glycolipid metabolism in the whole samples, and correlated with UACR, TNFα, and HIF1α in T2DM patients (P < 0.05). Ridge regression analysis showed that SIRT6 was a risk factor for both glycolipid metabolism and urinary protein (P < 0.05).

Conclusion

SIRT6 increases with biomarkers in glycolipid metabolism and urinary protein in different severities of diabetes and UACR, which is expected to be a potential biomarker for early prediction and diagnosis related to glycolipid metabolism disorders and related nephropathy.

Trial number: ChiCTR2000039808.

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Acknowledgements

Our team would like to thank the Clinical and Central Laboratory of the Fourth Affiliated Hospital of China Medical University, Laboratory of Nuclear Receptor and Major Metabolic Disease, and the Kidney Disease Center of Dalian Medical University for technical assistance and equipment support. This study was supported by the Doctoral Research Initiation Fund Project of Liaoning Province applied by HR.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of China Medical University, Shenyang, China

    Che Bian, Yuxia Wang & Jia Li

  2. Department of Gerontology, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Jing Gao

  3. Advanced Institute for Medical Sciences, Dalian Medical University, Lvshun South Road west 9, Dalian, 116044, Liaoning, China

    Zhilin Luan, Heyuan Lu & Huiwen Ren

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  1. Che Bian
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  2. Jing Gao
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  3. Yuxia Wang
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  4. Jia Li
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  5. Zhilin Luan
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  6. Heyuan Lu
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  7. Huiwen Ren
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Contributions

CB was involved in conceptualization, methodology, software, validation, formal analysis, investigation, resources, data curation, writing-original draft, visualization, project administration, and funding acquisition. JG helped in methodology, validation, formal analysis, resources, data curation, and writing—review & editing. YW, JL, ZL, and HL contributed to formal analysis, resources, and data curation. HR was involved in conceptualization, methodology, software, validation, formal analysis, investigation, data curation, writing-original draft, writing—review & editing, visualization, supervision, and funding acquisition. Details of the author's contribution are listed in Supplemental Table 1.

Corresponding author

Correspondence to Huiwen Ren.

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The authors declare that they have no conflicts of interest.

Human and animal rights

All human studies have been reviewed and approved by the Medical Ethics Committee of the Fourth Affiliated Hospital of China Medical University (Approval Number: EC-2020-KS-036) and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study, and details that might disclose the identity of the subjects under study were omitted.

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Bian, C., Gao, J., Wang, Y. et al. Association of SIRT6 circulating levels with urinary and glycometabolic markers in pre-diabetes and diabetes. Acta Diabetol 58, 1551–1562 (2021). https://doi.org/10.1007/s00592-021-01759-x

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