Dietary n-3 fatty acids intake and all-cause and cardiovascular mortality in patients with pre-diabetes and diabetes

Background: While the association between n-3 polyunsaturated fatty acids (PUFA) and
cardiovascular events has been thoroughly examined, there is still a scarcity of research
regarding their impact on the long-term prognosis in diabetic patients. Method: Herein, a total of
16,539 eligible individuals were enrolled from the National Health and Nutrition Examination
Survey (NHANES) 2003-2018, 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, 3,010 individuals died, with 989 deaths attributed to cardiovascular diseases.
Significantly lower risk of all-cause [T2: 0.81 (0.71, 0.92), T3: 0.77 (0.64, 0.94)] and
cardiovascular [T2: 0.75 (0.61, 0.93)] mortality was observed after adjusting for multivariable
compared to the reference (T1). Meanwhile, the RCS curve revealed a negative non-linear
association between the n-3 PUFA and mortality. None of the interactions in any subgroup
analysis were statistically significant except for BMI (p for interaction = 0.049). Finally, the WQS
analysis demonstrated alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) as the main
contributors to the n-3 PUFA benefits against mortality. Conclusions: Increased dietary intake of n-3 PUFA, particularly ALA and DPA, was associated with a reduced risk of all-cause and
cardiovascular mortality among Americans with prediabetes and diabetes.