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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1406382
This article is part of the Research Topic New Insights on Vascular and Metabolic Diabetic Complications View all 3 articles

Polyunsaturated Fatty Acids and Diabetic Microvascular Complications: A Mendelian Randomization Study

Provisionally accepted
Bingyang Liu Bingyang Liu 1Ruiyan Liu Ruiyan Liu 2Yi Gu Yi Gu 1,3Xiaoying Shen Xiaoying Shen 1Jianqing Zhou Jianqing Zhou 1Chun Luo Chun Luo 1*
  • 1 Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang Province, China
  • 2 Renji College of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • 3 Ningbo Institute for Medicine & Biomedical Engineering Combined Innovation, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47–0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62–0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

    Keywords: Diabetic microvascular complications, polyunsaturated fatty acids, Mendelian randomization, Omega-6, omega-3, Diabetic neuropathy, Diabetic Retinopathy, Diabetic kidney disease

    Received: 25 Mar 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 Liu, Liu, Gu, Shen, Zhou and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chun Luo, Ningbo Medical Centre Lihuili Hospital, Ningbo, 315010, Zhejiang Province, China

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