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Association of carotid atherosclerosis markers with all-cause and cardiovascular disease–specific mortality in persons with type 2 diabetes: a causal mediation analysis with glucose variation

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Abstract

Aims

Glucose variation (GV) is independently associated with mortality in patients with diabetes. However, no study has examined the effects of carotid atherosclerosis markers on mortality after considering GV. Our purpose is to investigate the independent effects of carotid atherosclerosis markers in persons with type 2 diabetes (T2DM) after considering GV and the mediation effects of carotid atherosclerosis markers on associations between GV with cardiovascular disease (CVD) mortality.

Materials and methods

This study is a retrospective cohort study including 3628 persons with T2DM who were admitted to a medical center between January 01, 2001 and October 31, 2021. GV was defined as a coefficient of variation (CV) of repeated measurements within a year before the index date (date of first IMT assessment). Carotid atherosclerosis markers included intima–media thickness (IMT), plaque, and stenosis. The outcomes consisted of all-cause and expanded cardiovascular disease (CVD) mortality. Cox proportional hazards models were applied.

Results

Among the participants, 286 (7.9%) had IMT ≥ 2 mm, 2834 (78.1%) had carotid plaque, and 464 (12.8%) had carotid stenosis ≥ 50%. When GV was considered, IMT, carotid plaque, and carotid stenosis were significant factors for all-cause mortality (except IMT considering HbA1c-CV) and expanded CVD mortality. IMT was a significant mediator in the associations of fasting plasma glucose (FPG)-CV with all-cause and expanded CVD mortality (2 and 3.19%, respectively), and carotid stenosis was a significant mediator in the association between FPG-CV and expanded CVD mortality (3.83%).

Conclusions

Our statistical evaluations show suggests that carotid atherosclerosis markers are important predictors of CVD mortality in persons with T2DM if GV is considered. In addition, IMT and carotid stenosis were significant mediators in the association between GV and mortality.

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Abbreviations

DM:

Diabetes mellitus

ASCVD:

Atherosclerotic cardiovascular disease

MI:

Myocardial infarction

IMT:

Intima–media thickness

FPG:

Fasting plasma glucose

HbA1c:

Glycated hemoglobin

DCMP:

Diabetes Care Management Program

CMUH:

China Medical University Hospital

ICD-9-CM:

International Classification of Disease, 9th Revision, Clinical Modification

LDL-C:

Low-density lipoprotein − cholesterol

HDL-C:

High-density lipoprotein − cholesterol

TC:

Total cholesterol

TG:

Triglyceride

BMI:

Body mass index

uACR:

Urine albumin − creatinine ratio

CV:

Coefficient of variation

eGFR:

Estimated glomerular filtration rate

CCAs:

Common carotid arteries

ICAs:

Internal carotid arteries)

CVD:

Cardiovascular disease

ICD-10-CM:

International Classification of Disease, Tenth Revision, Clinical

HR:

Hazard ratio

CI:

Confidence interval

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Funding

This study was supported primarily by the Ministry of Science and Technology of Taiwan (MOST 109-2314-B-039-031-MY2, MOST 110-2314-B-039-021- & MOST 111-2314-B-039-018-), National Science and Technology Council (NSTC 112-2314-B-039-042-) and China Medical University (CMU111-MF-86).

Author information

Author notes

  1. Cheng-Chieh Lin and Chia-Ing Li have equally contributed to this work.

Authors and Affiliations

  1. School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan, R.O.C.

    Cheng-Chieh Lin, Chia-Ing Li, Chiu-Shong Liu & Chih-Hsueh Lin

  2. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.

    Cheng-Chieh Lin, Chiu-Shong Liu & Chih-Hsueh Lin

  3. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.

    Chia-Ing Li

  4. Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., 406040, Taichung, Taiwan, R.O.C.

    Shing-Yu Yang & Tsai-Chung Li

  5. Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan, R.O.C.

    Tsai-Chung Li

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Contributions

CCL, CIL and TCL were responsible for drafting the article, the conception and design of the study. CIL acquired data and analysed data. CSL, CHL and SSY interpreted data. All authors revised the manuscript and approved the final version. CCL and TCL are responsible for the integrity of the work as a whole.

Corresponding author

Correspondence to Tsai-Chung Li.

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Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

This study was approved by the Ethical Review Board of China Medical University Hospital (CMUH111-REC1-001).

Informed consent

Informed consent of the study participants was not required because the dataset used in this study consists of de-identifed secondary data released for research purposes.

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Lin, CC., Li, CI., Liu, CS. et al. Association of carotid atherosclerosis markers with all-cause and cardiovascular disease–specific mortality in persons with type 2 diabetes: a causal mediation analysis with glucose variation. Acta Diabetol 61, 657–669 (2024). https://doi.org/10.1007/s00592-024-02243-y

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