Could circulating amino acids help refine risk assessment for type 2 diabetes mellitus (T2DM) in diverse populations? A population-based prospective cohort analysis from the MAUCO study, published in Cardiovascular Diabetology, examined associations between plasma amino acids and T2DM in 1,738 adults from Molina County, Central Chile. These participants were drawn from a larger cohort of 9,462 individuals aged 38 to 74 years enrolled in 2014, with a median follow-up of 4.3 years.

Circulating branched-chain amino acids (BCAAs), phenylalanine, tyrosine, alanine, glutamine, glycine, and histidine were measured using nuclear magnetic resonance. T2DM status was determined according to American Diabetes Association criteria at baseline and during follow-up. Associations between T2DM prevalence and incidence and demographic, lifestyle, and dietary factors were evaluated using multivariable logistic and Cox regression models, adjusted for these factors.

Cross-sectional analysis showed that higher plasma BCAAs were associated with T2DM (adjusted odds ratio [aOR] 2.1; 95% CI 1.80-2.50), along with alanine (aOR 1.57; 95% CI 1.37-1.80). In contrast, histidine (aOR 0.80; 95% CI 0.69-0.91), glycine (aOR 0.68; 95% CI 0.57-0.80), and glutamine (aOR 0.64; 95% CI 0.56-0.74) showed inverse associations.

During follow-up, 127 participants developed T2DM, corresponding to an incidence of 10.5%. Longitudinal analysis showed a similar overall pattern, although only higher isoleucine remained associated with incident T2DM (adjusted hazard ratio [aHR] 1.31; 95% CI 1.10-1.56). Elevated plasma BCAA concentrations were associated with T2DM prevalence, while only isoleucine was associated with incident T2DM.