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Thromb Haemost
DOI: 10.1055/a-2661-2537
Blood Cells, Inflammation and Infection

Diabetic Microvascular Disease and Risk of Peripheral Artery Disease, Foot Ulcer, Leg Infection, and Amputation

Fu-Shun Yen   *
1   Dr Yen's Clinic, Taoyuan, Taiwan
,
Yu-Hsin Yen   *
2   Duke-NUS Medical School, Singapore, Singapore
,
Yao-Min Hung
3   Department of Internal Medicine, Taitung Hospital, Ministry of Health and Welfare, Taitung, Taiwan
4   Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung, Taiwan
5   Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
6   College of Health and Nursing, Meiho University, Pingtung, Taiwan
,
James Cheng-Chung Wei
7   Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
8   Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
,
Fuu-Jen Tsai
9   School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
10   Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
11   Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan
12   Department of Medical Laboratory Science & Biotechnology, Asia University, Taichung, Taiwan
,
Yu-Tung Hung
13   Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
14   Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
,
Heng-Jun Lin
13   Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
14   Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
,
Chii-Min Hwu 
15   Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
16   Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
,
Chih-Cheng Hsu 
17   Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
18   Department of Health Services Administration, China Medical University, Taichung, Taiwan
19   Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
20   National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan
› Institutsangaben
Funding Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW112-TDU-B-212-144004), China Medical University Hospital (DMR-111-105; DMR-112-087), Taipei Veterans General Hospital (V113C-166, V114C-177), and the National Science and Technology Council, R.O.C. (NSTC113-2314-B-075-007-).
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Abstract

Background

Patients with diabetes are at risk for developing peripheral artery disease, foot ulcer, and amputation. We conducted this study to compare the risk of peripheral artery disease, foot ulcer, and amputation between patients with type 2 diabetes with and without microvascular disease.

Methods

We identified 1,013,154 patients aged 18 to 80 years and newly diagnosed with type 2 diabetes between January 1, 2008, and December 31, 2018, as the study participants. Cox proportional hazard models were used to compare the risk of diabetic foot disease between patients with and without diabetic kidney disease, diabetic retinopathy, and diabetic neuropathy.

Results

Patients with more types of microvascular disease were associated with a further increased risk of peripheral artery disease, foot ulcer, leg infection, and amputation compared to those without microvascular disease (p for trend <0.001). Patients with diabetic retinopathy were associated with a significantly increased risk of peripheral artery disease (aHR [95% CI] 1.12 [1.08, 1.16]), foot ulcer (1.50 [1.28, 1.75]), and amputation (2.53 [1.59, 4.01]) compared to those without microvascular disease. Individuals with diabetic neuropathy had a significantly higher risk of peripheral artery disease (1.27 [1.24, 1.29]), foot ulcer (1.27 [1.16, 1.40]), and leg infection (1.16 [1.12, 1.21]) compared to those without microvascular disease.

Conclusion

This nationwide cohort study showed that patients with type 2 diabetes and microvascular disease were associated with a higher risk of peripheral artery disease, foot ulcer, leg infection, and amputation than those without microvascular disease.

Keywords

diabetic kidney disease - diabetic neuropathy - diabetic retinopathy - leg infection - peripheral artery disease

Authors' Contribution

C.-C.H. and C.-M.H. contributed as guarantors of the study; F.-S.Y., Y.-H.Y., and C.-M.H. contributed to study design; Y.-M.H., J.C.-C.W., C.-C.H., H.-J.L., F.-J.T., and Y.-T.H. contributed to study coordination and data collection; C.-C.H., F.-J.T., H.-J.L., and Y.-T.H. contributed to data analysis; F.-S.Y., Y.-H.Y., Y.-M.H., J.C.-C.W., C.-C.H., and C.-M.H. contributed to manuscript writing. All authors participated in analysis and revising the manuscript. All authors contributed to the interpretation of the results and discussion.


Data Availability Statement

Data of this study are available from the National Health Insurance Research Database (NHIRD) published by Taiwan National Health Insurance (NHI) Administration. The data utilized in this study cannot be made available in the paper, the supplemental files, or in a public repository due to the “Personal Information Protection Act” enacted by Taiwan government starting from 2012. Requests for data can be sent as a formal proposal to the NHIRD Office (https://dep.mohw.gov.tw/DOS/cp-2516-3591-113.html) or by email to stsung@mohw.gov.tw.


* These authors contributed equally to this work.


Supplementary Material



Publikationsverlauf

Eingereicht: 22. Februar 2025

Angenommen: 18. Juli 2025

Artikel online veröffentlicht:
05. August 2025

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