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.
Level 3 - non-randomized controlled study
Pooled individual-participant meta-analysis of prospective observational cohort studies
PubMed 29032079 · doi:10.1016/S2213-8587(17)30307-8
What was done
This was a pooled meta-analysis of harmonized individual-level data from 20 prospective cohort studies across 10 countries (sampling baseline biomarkers between 1970 and 2010). The study evaluated 39,740 adults aged 49–76 years (cohort mean BMI 23.3–28.4 kg/m²) who were free of type 2 diabetes at baseline. Baseline proportions of linoleic acid and arachidonic acid biomarkers were measured across lipid compartments (phospholipids, plasma, cholesterol esters, and adipose tissue). The primary outcome was incident type 2 diabetes assessed prospectively over 366,073 person-years of follow-up, pooled using multivariable-adjusted inverse-variance weighted models.
What was found
Across follow-up, 4,347 incident cases of type 2 diabetes occurred. Higher circulating/tissue linoleic acid was associated with a lower risk of type 2 diabetes (multivariable RR per interquintile range 0.65, 95% CI 0.60–0.72, p < 0.0001; I² = 53.9%, p heterogeneity = 0.002). This inverse association was consistent across all measured lipid compartments. In contrast, arachidonic acid biomarkers were not significantly associated with diabetes risk (RR per interquintile range 0.96, 95% CI 0.88–1.05, p = 0.38; I² = 63.0%). Associations were not significantly modified by age, sex, BMI, race, aspirin use, omega-3 levels, or FADS gene variants (all p heterogeneity ≥ 0.13).
Why it matters
These findings challenge hypotheses that omega-6 polyunsaturated fatty acids promote metabolic dysfunction, showing instead that higher objective biomarkers of linoleic acid correlate strongly with reduced risk of type 2 diabetes.
Limits
Observational study design cannot prove causality or eliminate residual confounding from lifestyle factors. Biomarkers were assessed only at baseline and may not capture dietary changes over long follow-up intervals. Moderate-to-high statistical heterogeneity was observed across cohorts (I² = 53.9% for linoleic acid, I² = 63.0% for arachidonic acid).
Cited by
- supports In a pooled cohort consortium study, higher blood biomarker levels of linoleic acid were associated with a lower risk of developing type 2 diabetes.