LAUSR

Puerto Ricans are the second-largest Hispanic sub-group and have high rates of type 2 diabetes (T2D). Yet, there is limited understanding of the molecular pathways that contribute to cardiometabolic risk in this high-risk group. We hypothesized that circulating gut microbiota metabolites, which have been linked to T2D risk in non-Hispanic whites, are associated with a higher T2D likelihood and cardiometabolic risk markers among older Puerto Ricans. We developed a case-control study within the Boston Puerto Rican Health Study (BPRHS) with 275 prevalent T2D cases and 275 age and sex matched controls (mean age = 58.1 y, 71% female). We used LC/MS to measure baseline plasma gut microbiota metabolites (L-carnitine, betaine, choline, trimethylamine oxide [TMAO], and betaine: choline). We used conditional logistic regression to model the likelihood of prevalent T2D for each standard deviation (SD) increase in metabolites. Among controls free of T2D, we examined cross-sectional and prospective (2-year) linear associations (β [SD]) between metabolites and glycemia and dyslipidemia measures. After multivariable adjustment, significant differences in T2D likelihood [OR (95% CI)] were observed for each SD increase in L-carnitine [0.78 (0.62–0.99)], choline [1.33 (1.05–1.68)], betaine: choline [0.69 (0.54–0.88)], and TMAO [1.32 (1.04–1.67)]. We replicated findings for L-carnitine and betaine: choline in the WHI metabolomics study. Among BPRHS controls, cross-sectionally, higher betaine was associated with lower HOMA-IR (−9.97 [3.02]), insulin (−9.78 [2.83]), triglycerides (−11.4 [2.54]), and higher HDL-C (2.05 [0.65]). Prospectively, higher betaine and betaine: choline were associated with lower HOMA-IR (betaine −11.5 [3.63], betaine: choline −9.57 [3.68]), insulin (betaine −9.21 [3.27], betaine: choline −8.01 [3.31]), and glucose (betaine −2.17 [0.74], betaine: choline −1.58 [0.76]) concentrations, while higher choline was prospectively associated with higher triglycerides (5.17 [2.09]). No associations were seen between L-carnitine, TMAO, and cardiometabolic markers among controls. Plasma betaine, choline, and betaine: choline may be markers of cardiometabolic risk in this high-risk population. Future research should examine dietary and lifestyle correlates of betaine and choline. NIH.