Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis

Abstract

The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.

Plasma fatty acids as predictors of glycaemia and type 2 diabetes

“…In agreement with previous studies, n-3 fatty acids were not associated with the worsening of glycaemia or the risk of incident type 2 diabetes [15,25,37]. The DHA sufficiency index (ratio of 22:6n-3 to 22:5n-6) was associated with improved insulin sensitivity.…”

Influence of Ascorbic Acid Supplementation on Type 2 Diabetes Mellitus in Observational and Randomized Controlled Trials; A Systematic Review with Meta-Analysis

“…We could not see the beneficial effects of other antioxidants; eicosapentaenoic acid (59), or VE (63,65) with/without AA on FBS, this finding was similar to results obtained by previous metaanalysis in diabetics (13,101).…”

Serum Omega-3 Polyunsaturated Fatty Acids and Risk of Incident Type 2 Diabetes in Men: The Kuopio Ischemic Heart Disease Risk Factor Study

“…However, none of these studies found an association with incident type 2 diabetes either (7). Interestingly, these studies did not find an increased risk with higher concentrations in the studies from the U.S., suggesting that the higher risk could at least partly be related to the dietary assessment method (7).…”

“…In animal models, the long-chain omega-3 PUFAs have also been shown to decrease insulin resistance (4), but the results from randomized controlled trials in humans have generally found little benefits on glucose-insulin homeostasis (5,6). In prospective studies, the association between fish or EPA + DHA intake and risk of incident type 2 diabetes has been mixed (7)(8)(9)(10); in studies in the U.S., the association has even been positive (7,8). The random error inherited in dietary assessment methods can attenuate associations in dietary studies and thus could explain the null findings.…”

“…The random error inherited in dietary assessment methods can attenuate associations in dietary studies and thus could explain the null findings. Only a few studies have used an objective biomarker, circulating long-chain omega-3 PUFA concentration, as the exposure (7). However, none of these studies found an association with incident type 2 diabetes either (7).…”