THURSDAY, Jan. 22, 2026 (HealthDay News) -- A total of 235 metabolites are associated with incident type 2 diabetes (T2D), with a signature of 44 metabolites improving prediction of T2D, according to a study published online Jan. 14 in Nature Medicine.Jun Li, M.D., Ph.D., from Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues integrated blood metabolomic, genomic, and lifestyle data from up to 23,634 initially T2D-free participants from 10 cohorts to characterize metabolites associated with T2D risk.During up to 26 years of follow-up, the researchers found that 235 of the 469 metabolites examined were associated with incident T2D, including 67 associations that had not been reported previously across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine, and histidine pathways. These metabolites were linked to signaling pathways and clinical traits central to T2D pathophysiology in genetic analyses, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation, and liver function. Greater variations in T2D-associated versus nonassociated metabolites were explained by lifestyle factors, particularly physical activity, obesity, and diet, with specific metabolites revealed as potential mediators. A 44-metabolite signature improved risk prediction of T2D beyond conventional factors."A better understanding of the biological pathways behind disease can help drive the development of new treatments," Li said in a statement. "Our findings lay the groundwork for a deeper understanding of type 2 diabetes and may help inform the development of precision preventive strategies targeting specific metabolic pathways."One author disclosed ties to Westat.Abstract/Full Text.Sign up for our weekly HealthDay newsletter