Abstract Context While the association between n-3 polyunsaturated fatty acids (PUFAs) and cardiovascular (CV) events has been thoroughly examined, there is still a scarcity of research regarding their effect on the long-term prognosis in diabetic patients. Objective We aimed to explore the effects of n-3 PUFA on all-cause and cardiovascular mortality in patients with pre-diabetes and diabetes. Method Herein, a total of 16 539 eligible individuals were enrolled from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2018, and categorized into T1, T2, and T3 based on the tertiles of n-3 PUFA. The Cox proportional risk regression models, Kaplan-Meier curve, and subgroup analysis were conducted to evaluate the association between n-3 PUFA and mortality. Restricted cubic spline (RCS) curves graphically demonstrated the dose-response relationship. Additionally, weighted quantile sum (WQS) models were adopted to measure the mixed and individual effects of n-3 PUFA on mortality. Results Following a median follow-up period of 8.42 years, 3010 individuals died, with 989 deaths attributed to CV diseases. Significantly lower risk of all-cause (T2: 0.81 [0.71-0.92], T3: 0.77 [0.64-0.94]) and CV (T2: 0.75 [0.61-0.93]) mortality was observed after adjusting for multivariables compared to the reference (T1). Meanwhile, the RCS curve revealed a negative nonlinear association between n-3 PUFA and mortality. None of the interactions in any subgroup analysis were statistically significant except for BMI (P for interaction = .049). Finally, the WQS analysis demonstrated alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) as the main contributors to n-3 PUFAs’ benefits against mortality. Conclusion Increased dietary intake of n-3 PUFAs, particularly ALA and DPA, was associated with a reduced risk of all-cause and CV mortality among Americans with prediabetes and diabetes.
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