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HbA1c and the Risk of Lower Limb Ulcers Among Diabetic Patients: An Observational and Genetics Study

Guojun Guo1, Yunlong Guan2, Yuhuan Chen2

  • 1Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Journal of Diabetes Research
|April 7, 2025
PubMed

Insights

High blood sugar, measured by glycated hemoglobin (HbA1c), significantly increases the risk of developing lower limb ulcers in diabetic patients. Maintaining HbA1c below 53 mmol/mol is recommended to reduce ulcer incidence.

Area of Science:

  • Endocrinology
  • Diabetology
  • Vascular Medicine

Background:

  • Lower limb ulcers are a severe complication of diabetes mellitus.
  • The precise relationship between glycated hemoglobin (HbA1c) and lower limb ulceration requires further investigation.

Purpose of the Study:

  • To comprehensively assess the association between HbA1c levels and the risk of lower limb ulcers in diabetic individuals.
  • To explore potential causal links using observational and Mendelian randomization (MR) methods.

Main Methods:

  • A prospective cohort study involving 23,434 diabetic patients from the UK Biobank.
  • Utilized Cox proportional hazard models and one-sample Mendelian randomization analyses to evaluate HbA1c-ulcer risk association.

Main Results:

  • Over 290,677 person-years, 1101 lower limb ulcer cases were recorded.
  • Higher HbA1c levels demonstrated a dose-dependent increase in lower limb ulcer risk, particularly above 53 mmol/mol.
  • Mendelian randomization analyses indicated a positive, though not statistically significant, association.

Conclusions:

  • Elevated HbA1c levels are a significant risk factor for lower limb ulcers in the diabetic population.
  • An HbA1c target below 53 mmol/mol is suggested to mitigate the incidence of diabetic foot ulcers.

Keywords:
HbA1cMendelian randomizationcohort studydiabeteslower limb ulcer

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