Hypertension and the Risk of Diabetic Foot Ulcers: A Mendelian Randomization Analysis

Jiaxing Xin

doi:10.54097/8kbvja86

Authors

Jiaxing Xin

DOI:

https://doi.org/10.54097/8kbvja86

Keywords:

Hypertension, Diabetic Foot Ulcer, Mendelian Randomization

Abstract

Objective: This study utilized a two-sample Mendelian randomization (MR) approach to explore whether hypertension (HBP) has a causal influence on the development of diabetic foot ulcers (DFU). Methods: Summary statistics from genome-wide association studies (GWAS) involving European populations were analyzed. Genetic variants linked to hypertension were extracted from the FinnGen consortium, whereas diabetic foot ulcer data were obtained from the UK Biobank (UKBB). The primary analysis relied on the inverse variance weighted (IVW) method, supplemented by weighted median (WM) and MR-Egger regression to assess robustness. Results: The IVW analysis indicated a statistically significant association between hypertension and diabetic foot ulcers (OR = 2.107, 95% CI = 1.2028–3.692, P = 0.009). Sensitivity analyses confirmed the stability of these findings, with no significant heterogeneity (Cochran’s Q test) or evidence of horizontal pleiotropy detected. Conclusion: These findings suggest that hypertension may contribute to an elevated risk of diabetic foot ulcers, supporting a potential causal relationship between the two conditions.

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References

[1] Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †. Ann Med. 2017 Mar;49(2):106-116. doi: 10.1080/07853890.2016.1231932. Epub 2016 Nov 3. PMID: 27585063.

[2] Armstrong DG, Tan TW, Boulton AJM, Bus SA. Diabetic Foot Ulcers: A Review. JAMA. 2023 Jul 3;330(1):62-75. doi: 10.1001/jama.2023.10578. PMID: 37395769; PMCID: PMC10723802.

[3] Xia F. Effect of Traditional Chinese Medicine Fumigation on Patients with Diabetic Foot. Chin J Min Health Med. 2022;34(17):96-99.

[4] Wang XY. Study on Quality of Life and Its Influencing Factors Among Caregivers of Patients with Diabetic Foot Ulcer Amputation [D]. Qingdao University, 2023. DOI:10.27262/d. cnki.gqdau.2023.000058.

[5] Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. Diabetes Care. 1999 Jul;22 (7):1036-42. doi: 10.2337/diacare.22.7.1036. PMID: 10388963.

[6] Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12;293(2):217-28. doi: 10.1001/jama.293.2.217. PMID: 15644549.

[7] Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. doi: 10.1016/S0140-6736(05)17741-1. PMID: 15652604.

[8] Guidelines for the Prevention and Treatment of Diabetic Foot in China (2019). Chin J Diabetes. 2019;11(2):92-108.

[9] Wei HR, Ma L. Research Progress on Risk Factors of Diabetic Foot Ulcer. J Tradit Chin Med. 2024;42(02):145-148.

[10] Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004 Feb;33(1):30-42. doi: 10.1093/ije/dyh132. PMID: 15075143.

[11] Sekula P, Del Greco M F, Pattaro C, Köttgen A. Mendelian Randomization as an Approach to Assess Causality Using Observational Data. J Am Soc Nephrol. 2016 Nov;27 (11): 3253-3265. doi: 10.1681/ASN.2016010098. Epub 2016 Aug 2. PMID: 27486138; PMCID: PMC5084898.

[12] Yin K, Qiao T, Zhang Y, Liu J, Wang Y, Qi F, Deng J, Zhao C, Xu Y, Cao Y. Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis. BMJ Open Diabetes Res Care. 2023 Nov;11(6):e003523. doi: 10.1136/bmjdrc-2023-003523. PMID: 37989345; PMCID: PMC10660165.

[13] Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, VanderWeele TJ, Higgins JPT, Timpson NJ, Dimou N, Langenberg C, Golub RM, Loder EW, Gallo V, Tybjaerg-Hansen A, Davey Smith G, Egger M, Richards JB. Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement. JAMA. 2021 Oct 26;326 (16): 1614-1621. doi: 10.1001/jama.2021.18236. PMID: 34698778.

[14] Ma J, Li J, Jin C, Yang J, Zheng C, Chen K, Xie Y, Yang Y, Bo Z, Wang J, Su Q, Wang J, Chen G, Wang Y. Association of gut microbiome and primary liver cancer: A two-sample Mendelian randomization and case-control study. Liver Int. 2023 Jan;43(1):221-233. doi: 10.1111/liv.15466. Epub 2022 Nov 8. PMID: 36300678.

[15] Ru X, Huang L, Su Z, Ye C, Guo Y. Exploring the causal relationship between asthma in the metabolic syndrome: a Mendelian randomization study. J Asthma. 2024 Aug 20:1-38. doi: 10.1080/02770903.2024.2394143. Epub ahead of print. PMID: 39163002.

[16] Wang YZ, Shen HB. [Challenges and factors that influencing causal inference and interpretation, based on Mendelian randomization studies]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Aug 10;41(8):1231-1236. Chinese. doi: 10.3760/ cma.j. cn 112338-20200521-00749. PMID: 32867428.

[17] Zhu X, Huang S, Kang W, Chen P, Liu J. Association Between Polyunsaturated Fatty Acids and Parkinson's Disease: A Two-Sample Mendelian Randomization Study. Front Aging Neurosci. 2023 Feb 22;15:1123239. doi: 10.3389/fnagi. 2023. 1123239. PMID: 36909950; PMCID: PMC9992541.

[18] Chinese Diabetes Society. Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition, Part II). Chin J Pract Intern Med. 2021;41(9):757-784.

[19] Zaki SM, El Karsh DS, Faden TM, Almghamsi LT, Fathaldin JO, Alhazmi OA. Diabetic Foot Complications in Saudi Arabia: A Retrospective Study. Cureus. 2024 Feb 3;16(2):e53531. doi: 10. 7759/cureus.53531. PMID: 38445149; PMCID: PMC 1091 2821.

[20] Luo Y, Liu C, Li C, Jin M, Pi L, Jin Z. The incidence of lower extremity amputation and its associated risk factors in patients with diabetic foot ulcers: A meta-analysis. Int Wound J. 2024 Jul;21(7):e14931. doi: 10.1111/iwj.14931. PMID: 38972836; PMCID: PMC11227953.

[21] La salut a Barcelona 2019. Agència de Salut Pública de Barcelona. 2020. [consultado 22 Mar 2022]. Disponible en: https://www.aspb.cat/noticies/informe-salut-barcelona-2019/.

[22] Jeon BJ, Choi HJ, Kang JS, Tak MS, Park ES. Comparison of five systems of classification of diabetic foot ulcers and predictive factors for amputation. Int Wound J. 2017 Jun;14 (3): 537-545. doi: 10.1111/iwj.12642. Epub 2016 Oct 10. PMID: 27723246; PMCID: PMC7949506.

[23] Chen ZJ, Pan XY, Deng P, et al. Advances and Prospects in Local Wound Treatment for Diabetic Foot Ulcers. Chin J Foot Ankle Surg (Electronic Edition). 2022;9(04):95-100.

[24] Wang L, Zeng N, Xie WP, et al. Effects of Intensive Glycemic and Blood Pressure Control on Exosomal microRNAs in Patients with Diabetic Foot. Youjiang Med J. 2021;49(02):97-102.

[25] Zhang Y, Zhou DM, Li W, et al. Risk Factors of Diabetic Foot and the Impact of Ulcer Severity on Prognosis. Chin J Gerontol. 2021;41(22):4911-4914.