In the fast‑paced modern life, chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have quietly become “invisible killers” threatening our health. Faced with such a severe situation, in addition to weight control, regular exercise, and dietary intervention, the scientific community is turning its attention to a potential intervention strategy—dietary regulation, especially those little‑known “bioactive components” in daily foods that may play key roles.
Recently, a large‑scale cohort study from Tehran, Iran, lasting nearly 20 years and covering tens of thousands of people, titled Association between dairy‑derived bioactive peptides and the risk of type 2 diabetes mellitus and cardiovascular diseases: Tehran Lipid and Glucose Study (TLGS), explored the complex relationship between specific “bioactive peptides” in milk and dairy products and the risk of chronic diseases.
The Tehran Lipid and Glucose Study (TLGS) is one of the most influential long‑term cohort studies in the Middle East. Initiated in 1999, it covers more than 15,000 residents in Tehran with a mean follow‑up of 16.3 years, aiming to evaluate risk factors for chronic diseases among urban residents in Tehran. The present study included participants with complete dietary data from the third phase of TLGS and newly enrolled participants in the fourth phase (as baseline data), and each participant was followed up to the fifth and sixth phases of TLGS.
Analytic sample for T2DM:From 7,761 participants aged ≥18 years, those with pre‑existing T2DM, CVD, cancer, abnormal energy intake (<800 or >4,200 kcal/day), pregnancy/lactation, or missing data were excluded. Finally, 5,469 individuals were included (follow‑up rate: 92.96%).
Analytic sample for CVD:From 5,752 participants aged ≥30 years, those with pre‑existing CVD, cancer, abnormal energy intake, or pregnancy/lactation were excluded. Finally, 4,980 individuals were included (follow‑up rate: 99.88%).
Main findings:Analysis by tertiles of total dairy‑derived bioactive peptide intake showed that participants in the highest tertile were generally older, with higher body mass index (BMI) and high‑density lipoprotein cholesterol (HDL‑C). Meanwhile, their intakes of protein, total fat, potassium, calcium, total dietary fiber, and total dairy products were significantly higher than those in the lowest tertile.
When comparing T2DM vs. non‑T2DM and CVD vs. non‑CVD populations, there were no significant differences in dairy intake or levels of various dairy‑derived bioactive peptides (including antidiabetic, antihypertensive, and antioxidant subclasses). However, participants with T2DM differed significantly from those without in metabolic indicators such as BMI, waist circumference, triglycerides, fasting blood glucose, and HDL‑C. Similar differences in metabolic characteristics were observed between CVD and non‑CVD participants.
After adjusting for potential confounders including age, sex, BMI, physical activity, smoking, visceral adiposity index (VAI), energy, and other nutrients, high intake of κ‑casein‑derived peptides was significantly associated with an increased risk of T2DM (HR = 1.29, 95% CI: 1.01–1.64). No significant associations with T2DM risk were found for intake of total digestion‑resistant bioactive peptides (TDRBP), αs1‑casein, αs2‑casein, β‑casein, α‑lactalbumin, or β‑lactoglobulin‑derived peptides. Furthermore, no statistically significant associations were observed between any dairy‑derived bioactive peptides and the risk of incident CVD.
In conclusion, the findings suggest that although total intake of dairy bioactive peptides has little effect on CVD risk, certain specific peptides (such as heptapeptides, peptides with glycosylated residues, peptides with disulfide bonds, and κ‑casein‑derived peptides) may increase the risk of T2DM. These findings highlight the complex and diverse biological effects of dairy‑derived bioactive peptides.
To further understand these associations, further research including clinical trials and mechanistic studies is crucial to uncover potential pathways and guide dietary recommendations. In addition, exploring the interactions between dairy peptides, gut microbiota, and individual metabolic characteristics may provide important clues for revealing their mechanisms in health and disease.