Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

Abstract

Summary Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49–76 years with a BMI (range of cohort means) of 23∙3–28∙4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0∙65, 95% CI 0∙60–0∙72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0∙96, 95% CI 0∙88–1∙05; p=0∙38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0∙13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funding Funders are shown in the appendix.

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

“…Our finding that a higher relative concentration of omega-6 fatty acids was associated with decreased diabetes risk, whereas higher MUFA levels were associated with increased diabetes risk is consistent with previous investigations (29,30). Consistent with our results in young adults, a recent large-scale study pooling data from 20 prospective cohorts reported that higher levels of linoleic acid, the predominant omega-6 fatty acid, has long-term benefits for the prevention of type 2 diabetes (30). These fatty acids are likely reflective of both dietary composition and endogenous metabolism (31).…”

Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

“…LA biosynthesis and metabolism requires some of the same enzymes used for EPA synthesis and metabolism, including the production of downstream metabolites 32,33 . Moreover, LA's consumption in the western diet is [14][15][16][17][18] times the amount required to prevent LA deficiency 22,46 and LA's effects on insulin sensitivity are strongly debated [46][47][48][49][50][51][52][53] .…”

Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: a prospective study in Chinese

“…However, in a recent meta-analysis that consisted of 39,740 adults, only higher levels of 18:2n-6, but not 20:4n-6, were associated with a lower risk of type 2 diabetes (7). Moreover, inconsistent associations of 22:4n-6 or 22:5n-6 with CHD or type 2 diabetes were also reported in cohort studies among European populations (30,32).…”