Choline Metabolites Linked to 15-Year Diabetes Risk in Diverse Middle-Aged Adults, CARDIA Study Reveals

According to the study, the findings align with existing research highlighting choline metabolism's role in diabetes. However, the study expands on the current literature by examining a racially diverse, population-based cohort of early middle-aged adults, a group for whom preventive measures could be particularly impactful.

There has been growing interest in the potential role of choline metabolism in the development of diabetes. Most previous studies examining circulating choline metabolites and their link to diabetes risk have focused on older adults, often with a high prevalence of risk factors. Considering this, Katie A. Meyer, Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, and colleagues aimed to explore the association between choline metabolism and the risk of developing diabetes in a diverse cohort of early middle-aged adults, a population where preventive measures may be especially effective.

For this purpose, the researchers used data from year 15 of follow-up (2000-2001) in the CARDIA Study, which included 3,133 participants aged 33–45 years. Plasma levels of choline metabolites (choline, betaine, and trimethylamine N-oxide [TMAO]) were measured. The researchers quantified the associations between these metabolites and the 15-year risk of incident diabetes (n = 387) among participants who were free of diabetes at baseline.

Cox proportional hazards regression models were used to adjust for sociodemographic factors, health behaviors, and clinical variables in the analysis.

The findings of the study are as follows:

• Betaine was inversely associated with the 15-year risk of incident diabetes, with a hazard ratio of 0.76 per 1-SD increase in betaine levels.
• TMAO was positively associated with the 15-year risk of incident diabetes, with a hazard ratio of 1.11 per 1-SD increase in TMAO levels.
• Choline was not significantly associated with the 15-year risk of incident diabetes, with a hazard ratio of 1.05 per 1-SD increase in choline levels.

"Given existing literature and findings from the population-based study in early middle-aged adults, further research is needed to identify factors that may influence the link between plasma betaine and diabetes risk. Notably, the inverse association between betaine and diabetes risk in men but not women requires validation in larger samples. Additionally, studies like Mendelian randomization and larger trials are needed to assess causality and explore whether dietary modifications of betaine could reduce diabetes risk," the researchers wrote.

"These results suggest that higher levels of circulating betaine may help reduce the risk of diabetes, potentially through the adoption of recommended healthy lifestyle changes," they concluded.

Reference:

Jessica K. Sprinkles, Anju Lulla, Autumn G. Hullings, Isis Trujillo-Gonzalez, Kevin C. Klatt, David R. Jacobs, Ravi V. Shah, Venkatesh L. Murthy, Annie Green Howard, Penny Gordon-Larsen, Katie A. Meyer; Choline Metabolites and 15-Year Risk of Incident Diabetes in a Prospective Cohort of Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study. Diabetes Care 21 October 2024; 47 (11): 1985–1994. https://doi.org/10.2337/dc24-1033