Abstract

Objective: Data from animal models supports a role for metabolites in the choline pathway in glycemic control and diabetes. Cross-sectional and case-control studies have documented positive associations between trimethylamine N-oxide (TMAO) and prevalent diabetes, but these findings have not been replicated in prospective analysis. Circulating choline has been positively, and betaine negatively, associated with diabetes in some, but not all, prospective data. We tested associations between three metabolites in the choline pathway (TMAO, choline, betaine) and 15-year incident diabetes in a diverse cohort of early-middle-aged adults. Methods: Study participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter cohort of Black and White Americans established in 1985/86 (baseline n=5,115; ages 18-30). Plasma concentrations of TMAO, choline, and betaine were measured from Year 15 (2000-01) stored plasma (-70°C) with liquid chromatography mass spectrometry (LC-MS). Logistic regression was used to quantify associations between plasma metabolites and diabetes, adjusting for sociodemographic, behavioral, and clinical covariates. Results: Among 3,317 participants without diabetes at Year 15, n=373 developed diabetes over 15 years of follow-up (2000-2016). Plasma TMAO and choline were not significantly associated with incident diabetes in all multivariable-adjusted models, while betaine was negatively associated with incident diabetes in all models (Table). Conclusion: In this population-based cohort of early-middle-aged US adults, plasma TMAO and choline were not associated with incident diabetes over 15 years of follow-up, while plasma betaine was negatively associated with incident diabetes.

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