Background: Type 2 diabetes (T2D) is a complex disease driven by lifestyle and genetic factors. The extent to which dietary fat quality may modify T2D genetic burden on the incidence of T2D is unknown.

Methods: We used Cox proportional-hazards models to calculate adjusted hazard ratios (HRs) for T2D among 103,2participants of European descent from 15 prospective cohort studies. T2D genetic risk profile was characterized by a 68-variant genetic risk score (GRS) weighted by published effect sizes. Diet was recorded using validated cohort-specific dietary assessment tools.

Findings: During a median follow-up of 12 years, 20,451 participants developed T2D. The relative risk of T2D per increment of 10 risk alleles in the GRS was 1.68 (95% confidence interval [CI] 1.62-1.74). Increasing monounsaturated fat intake in place of carbohydrates was associated with a higher risk of T2D (HR per 5% of energy 1.08, 95% CI 1.02-1.15), while increasing polyunsaturated or total ω-3 fat intake in place of carbohydrates was associated with a lower risk of T2D (HR per 5% of energy 0.92, 95% CI 0.85-1.00; and HR per increment of 1g/d 0.95, 95% CI, 0.92-0.99, respectively). We did not observe evidence of significant interactions between dietary fat subtypes and GRS on the risk of T2D.

Interpretation: In the present long-term prospective study including 103,2participants, our results support that genetic risk profile and monounsaturated fat intake were each associated with a higher risk of T2D, whereas polyunsaturated fat intake was associated with a lower risk of T2D. Findings from this study suggest that dietary fat recommendations do not need to be tailored to individual T2D genetic risk profile for the primary prevention of T2D, and that dietary fat subtypes associate with the risk of T2D across the spectrum of T2D genetic risk.


J. Merino: None. H.S. Dashti: None. M. Guasch: None. C. Ellervik: None. C. Smith: None. T.O. Kilpelainen: None. D. Chasman: None. J.C. Florez: Consultant; Self; Intarcia Therapeutics, Inc.. Consultant; Spouse/Partner; Santen.

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