Peripheral artery disease mediating the effect of metabolic syndrome related diseases on lower limb ulcers: Mendelian randomization analysis

Front Endocrinol (Lausanne). 2024 Feb 15:15:1345605. doi: 10.3389/fendo.2024.1345605. eCollection 2024.

Abstract

Background: Previous observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored.

Method: This research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD.

Results: Univariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD.

Conclusion: Hypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.

Keywords: Mendelian randomization; body mass index; hypertension; hyperuricemia; peripheral artery disease; type 2 diabetes; ulcers of lower limb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / genetics
  • Humans
  • Hypertension*
  • Hyperuricemia* / complications
  • Hyperuricemia* / epidemiology
  • Hyperuricemia* / genetics
  • Lower Extremity
  • Mendelian Randomization Analysis
  • Metabolic Diseases*
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / epidemiology
  • Metabolic Syndrome* / genetics
  • Obesity
  • Peripheral Arterial Disease* / complications
  • Peripheral Arterial Disease* / epidemiology
  • Peripheral Arterial Disease* / genetics
  • Ulcer

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Natural Science Foundation of Liaoning Province (2021-BS-215), Liaoning Revitalization Talents Program (XLYC1802014), Liaoning Key Research and Development Planning Project (2017226015), Liaoning BaiQianWan Talents Program, Distinguished Professor Project of Liaoning Province, Dalian outstanding youth science and technology talent project (2015R003) and Dalian Medical Science Research Program (20Z12001, 2112013).