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Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study

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Abstract

Aims

Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM).

Methods

After 1:1 matching by sex, age, body mass index, glycated haemoglobin A1c, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1 mm (abnormal C-IMT) and 231 patients with C-IMT of < 1 mm (normal C-IMT). C-IMT was assessed using ultrasonography. The serum metabolic profiling of fasting blood samples was performed using liquid chromatography-tandem triple quadrupole mass spectrometer coupled with the multivariate and univariate statistical analysis.

Results

Patients with abnormal C-IMT had significantly higher deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) levels, and lower levels of taurocholic acid (TCA) than those with normal C-IMT. Conditional logistic regression analysis revealed that per 1-standard deviation increase of DCA, TDCA and TCA were significantly associated with 64.7% (95% CI: 1.234–2.196) and 38.5% (95% CI: 1.124–1.706) higher, and 26.8% (95% CI: 0.597–0.897) lower risk of abnormal C-IMT, after adjustment of confounders. The addition of DCA, TCA, or DCA × TDCA/TCA ratio significantly improved the discrimination of abnormal C-IMT over traditional risk factors.

Conclusions

Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation.

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Availability of data and materials

The datasets used and/or analysed during the current study are not publicly available due to the individual privacy of the patients included in this study, but are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Abbreviations

ASCVD:

Atherosclerotic cardiovascular disease

AUC:

Areas under the curves

BMI:

Body mass index

CAD:

Coronary artery disease

C-IMT:

Carotid intima-media thickness

DBP:

Diastolic blood pressure

DCA:

Deoxycholic acid

EDC·HCl:

N-Ethyl-N’-(3-dimethylaminopropyl) carbodiimide hydrochloride

FC:

Fold change

FXR:

Farnesoid X receptor

HbA1c :

Glycated haemoglobin A1c

HDL-c:

High-density lipoprotein cholesterol

IMT:

Intima-media thickness

LC-TQMS:

Liquid chromatography-tandem triple quadrupole mass spectrometer

LDL-c:

Low-density lipoprotein cholesterol

OPLS-DA:

Orthogonal partial least squares-discriminant analysis

ROC:

Receiver operating characteristic

SBP:

Systolic blood pressure

SD:

Standard deviation

T2DM:

Type 2 diabetes mellitus

TC:

Total cholesterol

TCA:

Taurocholic acid

TDCA:

Taurodeoxycholic acid

TG:

Triglyceride

TGR5:

Takeda G protein-coupled receptor 5

VIP:

Variable importance in the projection

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Acknowledgements

We are very grateful to all the staff for helping with the present study. We are grateful to all participants for their dedication to data collection and laboratory measurements.

Funding

This work was funded by Natural Science Foundation of Shanghai (17ZR1421300).

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Author notes

  1. Jiaorong Su and Qing Zhao are contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai, 200233, China

    Jiaorong Su, Wei Zhu, Jingyi Lu & Xiaojing Ma

  2. Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Qing Zhao, Aihua Zhao & Wei Jia

  3. School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China

    Wei Jia

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  1. Jiaorong Su
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Contributions

XM and JL contributed to study design. JS contributed to data collection, data analysis, and writing the paper. QZ and AZ performed the data analysis and the LC-TQMS-based metabolomics. WZ contributed to the sample collection. AZ, WJ, JL, and XM revised the paper and contributed to the discussion. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jingyi Lu or Xiaojing Ma.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and was in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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All participants provided written informed consent prior to their inclusion in the study.

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Su, J., Zhao, Q., Zhao, A. et al. Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study. Acta Diabetol 58, 1217–1224 (2021). https://doi.org/10.1007/s00592-021-01717-7

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  • DOI: https://doi.org/10.1007/s00592-021-01717-7

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