Association between dairy-derived bioactive peptides and the risk of type 2 diabetes mellitus and cardiovascular diseases: Tehran lipid and glucose study.

Cardiometabolic diseases, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) are escalating globally, posing significant health challenges. While dairy products and their bioactive peptides (BPs) may influence chronic diseases risk, the evidence remains inconsistent. These peptides may act via modulation of gut microbiota, reducing inflammation, and regulating lipid metabolism. The current study aimed to investigate the possible association between dairy-derived BPs (DDBPs) and the risk of T2DM and CVDs in Iranian adult population within the framework of Tehran Lipid and Glucose Study (TLGS). In this population-based cohort study, 5,469 participants (T2DM analysis) and 4,980 participants (CVDs analysis) from the TLGS were followed for a mean follow-up period of 6 years. Dietary intake data were determined using a validated food-frequency-questionnaire. Various types of DDBPs were estimated via in-silico proteolysis simulations. The association of bioactive peptides with T2DM and CVDs risk were determined using Cox proportional hazards regression models. Higher intake of k-casein-derived peptides (HR:1.21;95% CI: 1.01-1.64), Hepta-peptides (HR:1.31;95% CI:1.02-1.67), peptides with glycosylated residues (HR:1.29;95%CI: 1.01-1.65), glycosylated residues (HR:1.39;95% CI: 1.07-1.80), and disulfide bond- containing peptides (HR:1.34;95% CI: 1.05-1.71) was associated with an elevated T2DM risk in the adjusted model. Dairy protein intake (highest vs. lowest tertile: HR:1.29;95% CI: 1.02-1.62) Also increased T2DM risk, while total dairy intake showed no association. No significant associations were found between DDBPs, dairy intake, or dairy protein intake and the risk of CVDs. Our results showed that specific DDBPs particularly k-casein-derived fragments and structurally modified peptides (including hepta-peptides, glycosylated peptides, and peptides with disulfide bonds), were associated with an increased risk of T2DM in Tehranian adults. Further studies are warranted to elucidate these associations.