Fig. 3: Mediation analysis.

A Adjusted effect estimates (beta coefficients) of red meat on T2D-related (dh)ceramides (direction of associations consistent with mediation hypothesis; p-values < 0.05, one-sided t-test). B Attenuation of the putative effect of red meat on T2D risk after adjustment for red meat- and T2D-related (dh)ceramides. C Adjusted effect estimate (beta coefficient) of coffee on T2D-related dhCer22:2 (direction of the association consistent with the mediation hypothesis; p-value < 0.05, one-sided t-test). D Attenuation of the putative effect of coffee on T2D risk after adjustment for coffee- and T2D-related dhCer22:2. All models were extensively adjusted for potential confounders (age, sex, fasting status, total energy intake, leisure-time physical activity, medication, smoking, alcohol consumption, and education). Blue indicates inverse association (i.e., lower ceramide concentration or T2D risk), orange: positive association (i.e., higher ceramide concentration or T2D risk). Total effect is the confounder-adjusted hazard ratio (95% CI) per exposure unit: red meat, 2 SD (~1 portion per day); coffee, two cups (300 mL) per day. PE Proportion explainable, i.e., relative attenuation of the total effect through mediator-adjustment. Cer ceramide, dhCer dihydroceramide.