Circulating amino acids and Type 2 diabetes in a Latin American population-based cohort

Metabolomics enables the identification of circulating biomarkers for Type 2 diabetes (T2D). Most studies of circulating amino acids and T2D are from European and Asian, few from Latin America. We aimed to evaluate plasma amino acids and risk of T2D in an agricultural population from Molina County, Central Chile.

MAUCO is a population-based prospective cohort of 9462 participants aged 38 to 74 years at enrollment in 2014. From 2000 participants (47% women) selected for metabolomic analysis 1738 had enough serum sample for this study. We quantified circulating branched-chain amino acids (BCAAs), as well as phenylalanine, tyrosine, alanine, glutamine, glycine, and histidine using nuclear magnetic resonance, while T2D was diagnosed according to the American Diabetes Association guidelines at enrollment and follow-up. We analyzed the association of the circulating amino acids on T2D prevalence and incidence, using multiple logistic and Cox regression models adjusted by sex, age, education, body mass index, smoking, alcohol consumption, physical activity, and Mediterranean diet score.

In the cross-sectional analysis, plasma BCAAs (aOR 2.1; 95% CI 1.80-2.50), and plasma alanine (aOR 1.57; 95% CI 1.37-1.80) were associated with T2D, while histidine, glycine, and glutamine were inversely associated with T2D risk (aOR 0.80; 95% CI 0.69-0.91; 0.68; 95% CI 0.57-0.80, and 0.64; 95% CI 0.56-0.74, respectively). After a median follow-up of 4.3 years, we diagnosed 127 (10.5% incidence) new T2D cases. Prevalence and incidence analysis yielded a similar pattern, but only high isoleucine reached statistical significance in the incidence of T2D (aHR 1.31; 95% CI 1.10-1.56).

Elevated plasma BCAA concentrations in Chilean adults were significantly associated with the prevalence of T2D, while only high isoleucine was associated with the incidence of T2D. These findings could inform risk stratification by specific metabolic mechanisms and guide future research on targeted interventions.