Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications Among Individuals With Type 2 Diabetes

Objective To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among people with type 2 diabetes and to further explore the potential mediating role of metabolism-related biomarkers.Research Design and Methods This study included 20 338 participants with type 2 diabetes from the UK Biobank. Diabetic complications were identified through hospital inpatient records.Results During 13.2 years of follow-up, 5396 people developed macrovascular complications, and 4868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD, and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammatory markers collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD.Conclusion Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.