Background: Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain
and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited
evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with
heterogeneity of dietary intake.
Methodology/Principal Findings: A case-cohort study was nested within the European Prospective Investigation into
Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident
diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy
(kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prenticeweighted
Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects
meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort
members, varying across countries (range 1.4–1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol
intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and
T2D (HR 1.02 (95% CI: 0.93–1.13), which was consistent across countries (I
2 = 2.9%).
Conclusions/Significance: In this large European case-cohort study no association between DED of solid and semi-solid
foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an
association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current
WHO recommendations to prevent chronic diseases