Higher intake of dietary dicarbonyl compounds is associated with lower incidence of type 2 diabetes: European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study

Purpose: Dicarbonyls are reactive precursors of advanced glycation end-products. They are formed during food processing, and endogenously in humans during glycolysis and lipid peroxidation. Higher plasma dicarbonyls, particularly methylglyoxal (MGO), promote insulin resistance and type 2 diabetes, but the association between dietary dicarbonyls intake and type 2 diabetes is unknown. This study examined the associations between dietary dicarbonyls and type 2 diabetes incidence. Methods: 11,995 incident type 2 diabetes cases and a sub-cohort of 15,797 controls from the prospective multi-center European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct cohort were included. Intakes of three major dicarbonyls MGO, glyoxal [GO], and 3-deoxyglucosone [3-DG] were estimated at baseline using dietary questionnaires. Type 2 diabetes risk according to dietary dicarbonyl intake was estimated by multivariable-adjusted hazard ratios from Prentice-weighted Cox-regression analyses. Results: Higher intakes of MGO (sample-specific mean intake 3.4 ± 1.3 mg/d) and 3-DG (13.8 ± 10.5) were associated with lower incidence of type 2 diabetes (HR 0.92 [95% CI 0.90–0.95] for 1 SD higher MGO intake and 0.93 [0.90–0.95] for 1 SD higher 3-DG intake). No associations were observed for dietary GO. Conclusion: Participants who consumed more dietary dicarbonyls MGO and 3-DG had a lower risk to develop type 2 diabetes. This protective association contrasts with the harmful effects on type 2 diabetes risk reported for endogenously formed dicarbonyls. Supplementary information: The online version contains supplementary material available at 10.1007/s00394-026-03904-0.