Department of Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China.
Wenzhou Medical University Renji College, Wenzhou, China.
Front Endocrinol (Lausanne). 2024 Aug 7;15:1406382. doi: 10.3389/fendo.2024.1406382. eCollection 2024.
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, = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, = 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.
背景：观察性研究和临床试验表明，多不饱和脂肪酸（PUFAs）可能有助于预防糖尿病微血管并发症。然而，由于研究结果存在冲突，这些关系的因果性质仍然不清楚。本研究采用孟德尔随机化（MR）来评估 PUFAs 对糖尿病微血管并发症的因果影响。
方法：我们使用英国生物库（UK Biobank）的数据确定了 PUFAs（特别是 omega-3 和 omega-6 脂肪酸）的工具变量。糖尿病微血管并发症的结果数据来自芬兰遗传研究（FinnGen Study）。我们的分析涵盖了 1 型和 2 型糖尿病的微血管结局，即糖尿病神经病变（DN）、糖尿病视网膜病变（DR）和糖尿病肾病（DKD）。进行了逆孟德尔随机分析，以检查糖尿病微血管并发症对 PUFAs 的影响。进行了敏感性分析以验证结果的稳健性。最后，进行了多变量孟德尔随机化（MVMR）分析，以确定 PUFAs 是否对糖尿病微血管并发症有直接影响。
结果：研究表明，遗传预测的 omega-6 脂肪酸水平升高可显著降低 2 型糖尿病中 DN 的风险（优势比（OR）：0.62，95%置信区间（CI）：0.47-0.82， = 0.001）。还提示 2 型糖尿病中对 DR 有保护作用（OR：0.75，95% CI：0.62-0.92， = 0.005）。MVMR 分析在调整潜在混杂因素后证实了这些结果的稳定性。在 2 型糖尿病中，omega-6 脂肪酸对 DKD 或 1 型糖尿病的任何并发症均无显著影响。相比之下，omega-3 脂肪酸与评估的任何糖尿病微血管并发症均无显著因果关系。
结论：我们的 MR 分析揭示了 omega-6 脂肪酸与 2 型糖尿病中某些糖尿病微血管并发症之间的因果关系，为进一步研究糖尿病微血管并发症的机制和临床治疗提供了新的思路。
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