Diabetes, a metabolic disease, is on the rise worldwide, and over 90 percent of cases are type 2 diabetes, in which the body does not effectively respond to insulin. Researchers from Mass General Brigham and Albert Einstein College of Medicine identified metabolites (small molecules found in blood generated through metabolism) associated with risk of developing type 2 diabetes in the future and revealed genetic and lifestyle factors that may influence these metabolites. They also developed a metabolomic signature that predicts future risk of type 2 diabetes beyond traditional risk factors. Their results are published in Nature Medicine.
In this study, researchers tracked 23,634 individuals with diverse ethnic backgrounds across 10 prospective cohorts with up to 26 years of follow-up. These individuals were initially free of type 2 diabetes. The team analyzed 469 metabolites in blood samples, as well as genetic, diet, and lifestyle data, to see how they relate to risk of developing type 2 diabetes. Of the metabolites examined, 235 were found to be associated with a higher or lower risk of developing type 2 diabetes, 67 of which were new discoveries.
“Interestingly, we found that diet and lifestyle factors may have a stronger influence on metabolites linked to type 2 diabetes than on metabolites not associated with the disease,” said first and co-corresponding author Jun Li, MD, PhDan assistant professor of Medicine and associate epidemiologist in the Mass General Brigham Department of Medicine. Li is also an assistant professor in the Department of Nutrition at Harvard T.H. Chan School of Public Health. “This is especially true for obesity, physical activity, and intake of certain foods and beverages such as red meat, vegetables, sugary drinks, and coffee or tea. Increasing evidence suggests that these dietary and lifestyle factors are associated with greater or lower risk of type 2 diabetes. Our study revealed that specific metabolites may act as potential mediators, linking these factors with type 2 diabetes risk.”
The metabolites associated with type 2 diabetes were also found to be genetically linked to clinical traits and tissue types that are relevant to the disease. Furthermore, the team developed a unique signature of 44 metabolites that improved prediction of future risk of type 2 diabetes.
“Our study is the largest and most comprehensive investigation of blood metabolic profiles associated with the risk of type 2 diabetes that integrates genomic and diet and lifestyle data from a wide range of people, and lays important groundwork for future studies,” said senior and co-corresponding author Qibin Qi, PhD, professor in the Department of Epidemiology & Population Health and associate director of that department’s Center for Population Cohorts at Albert Einstein College of Medicine.
Reference: Li J, Hu J, Yun H, et al. Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes. Night With. 2026. doi: 10.1038/s41591-025-04105-8
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