Clin Nutr. , 2018., Sep 26. pii: S0261-5614(18)32456-7. doi: 10.1016/j.clnu.2018.09.018.

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.

Zheng JS, Lin JS, Dong HL, Zeng FF, et al.

BACKGROUND & AIMS: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. METHODS: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. RESULTS: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). CONCLUSIONS: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.

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Prospective associations between dietary n-3 polyunsaturated fatty acids (PUFA) and type 2 diabetes (T2D) have been inconsistent in the published literature. Several prior meta-analyses have suggested that overall dietary intake of marine n-3 PUFA (including docosahexaenoic acid [DHA, C22:6n-3], docosapentaenoic acid [DPA, C22:5n-3] and eicosapentaenoic acid [EPA, C20:5n-3]) was not associated with incident T2D, but reflected substantial heterogeneity by geographic region. Using objectively measured circulating biomarkers of n-3 PUFA to examine the association with T2D could overcome the above limitations of dietary measurement. The aim of the present study was to investigate the association between objectively measured individual n-3 PUFA in red blood cells (erythrocytes) and incident T2D in a community-based prospective cohort study in southern China. It was hypothesized that erythrocyte marine n-3 PUFA were inversely associated with incident type 2 diabetes in the Chinese population.

 

The results of the present prospective cohort study among a community-based Chinese population suggest that levels of erythrocyte marine n-3 PUFA: DPA and EPA were inversely associated with risk of incident T2D, while there was no association for erythrocyte DHA or ALA. However, the effect size of the present study was very similar to that of the Shanghai Women’s Health study and suggested an inverse association of dietary marine n-3 PUFA with T2D risk. Objective measurements of n-3 PUFA in blood (including erythrocyte, plasma, serum and whole blood, or related lipid fractions) have been widely adopted by the scientific community as biomarkers of dietary n-3 PUFA intake. However, due to the high cost and time-consuming nature of blood fatty acid measurement, only a few prospective studies have reported the associations between blood n-3 PUFA biomarkers and T2D incidence. Most studies have focused on Western populations. Meanwhile the prospective evidence from Asia is rare, with only one nested case-control study (336 T2D cases) in Japan published very recently, reporting a null association. The reason for the inconsistencies between the results from our cohort and Western cohorts might be because levels of marine n-3 PUFA (median: DPA 1.54% and EPA 0.55%) in this cohort were lower than those found in Western cohorts using measurement of erythrocyte or erythrocyte phospholipid fatty acids (median: DPA >2.2%, EPA>0.75%). Though a potential threshold effect/non-linear association might exist, it was not observed in this study.

 

The study did not find a significant association between T2D and erythrocyte ALA. This result conflicts with previous findings from the EPIC-InterAct and its comparative meta-analysis that circulating ALA was inversely associated with T2D. The reason for this inconsistency is unclear. The study shows that erythrocyte EPA and DPA, as biomarkers of dietary marine n-3 PUFA intake, are associated with lower incidence of T2D. The current results regarding erythrocyte biomarkers add to the evidence that dietary intake of marine n-3 PUFA is associated with lower risk of T2D in Asian populations. Detailed investigation of the potential causality of total and individual marine n-3 PUFA in T2D etiology is warranted, using a Mendelian randomization approach in observational studies or randomized controlled trials, especially among Asian participants.