Researchers from Mass General Brigham and Albert Einstein College of Medicine have identified patterns in circulating blood metabolites that may help identify individuals at risk of developing type 2 diabetes (T2D) well before clinical symptoms appear. The findings were published in Nature Medicine.
The study followed up to 23,634 initially diabetes-free individuals across diverse racial and ethnic backgrounds for up to 26 years. From 469 metabolites analysed, researchers identified 235, including 67 newly described, associated with future T2D risk. These associations held even after adjusting for conventional risk factors such as obesity, blood pressure, lipid levels, and lifestyle variables.
The team also examined genetic and lifestyle contributors to these metabolite profiles. Lifestyle factors, particularly physical activity, diet, and obesity, explained a greater share of variability in diabetes-associated metabolites than in those unlinked to the disease. Certain metabolites appeared to act as intermediaries connecting lifestyle behaviours, such as coffee consumption and physical activity, to future diabetes risk, though the study’s observational design means causality cannot be established.
In a final phase, researchers developed a 44-metabolite risk signature that improved long-term T2D prediction beyond standard clinical markers, including age, BMI, sex, and blood glucose. The signature was validated across multiple cohorts and showed consistent results.
The authors note that around 77% of participants were non-Hispanic White, limiting generalisability, and call for studies in more diverse populations. Randomised trials are also needed to test whether lifestyle interventions can meaningfully alter these metabolite patterns and reduce disease risk.
Mass General Brigham / Albert Einstein College of Medicine | Nature Medicine, 2026
