Research from the Nutrition Research Institute (NRI) sheds new light on the connection between choline metabolism and diabetes risk, focusing on a critical age range—adults in their 30s and 40s—when metabolic changes begin to take shape. The study, led by NRI scientists Anju Lulla, PhD, Isis Trujillo-Gonzalez, PhD, and Katie Meyer, ScD, along with her doctoral student Jessica K. Sprinkles, examines how two key metabolites—betaine and trimethylamine-N-oxide (TMAO), both derived from the nutrient choline—influence the likelihood of developing diabetes over 15 years.
💡 What is a metabolite?
A metabolite is a substance produced when the body breaks down food, drugs, or other compounds during metabolism. In this study:
- Choline is the starting nutrient found in foods like eggs and meat.
- Betaine is produced when the liver and kidneys oxidize choline.
- TMAO is formed when gut bacteria break down choline into trimethylamine, which is then processed by the liver into TMAO.
Choline is an essential nutrient that plays several roles in the body, including serving as a precursor for the production of betaine and TMAO. These metabolites are involved in regulating blood sugar levels, and this study aimed to determine whether their levels in the body can predict diabetes risk and guide future prevention efforts.
Key Findings
- Betaine’s Protective Role: The research found that participants with higher levels of betaine were significantly less likely to develop diabetes over the 15-year study period. This suggests that betaine could serve as a useful biomarker—a measurable indicator of lower diabetes risk.
- TMAO’s Risky Role: While higher levels of TMAO were associated with increased diabetes risk, these findings were not consistent across all analyses, indicating the need for further study to confirm TMAO’s role.
- Choline’s Neutral Role: Choline itself showed no clear association with diabetes risk, suggesting it may not be a predictor of the disease.
Study Design
The research is part of the ongoing CARDIA study, which follows a diverse group of adults and focuses on investigating the determinants of cardiovascular disease and risk factors throughout life. For this analysis, researchers measured participants’ blood levels of choline, betaine, and TMAO and tracked new cases of diabetes over 15 years. They also accounted for lifestyle and health factors such as diet, physical activity, and kidney function.
NRI’s Collaborative Approach
The collaboration between Katie Meyer and Kevin Klatt, PhD from the University of California, Berkeley, originated from the Future Directions in Choline symposium hosted by the NRI in November 2023. This event brought together experts in the field, sparking discussions that led directly to this research. The study reflects the NRI’s ongoing efforts to foster interdisciplinary collaborations that advance the science of nutrition.
Implications for Prevention
The findings emphasize the value of preventive efforts during early middle age, when individuals often experience shifts in metabolic health. Checking betaine levels could become a way to identify people at higher risk of diabetes and provide opportunities for targeted lifestyle interventions.
While TMAO’s role remains uncertain, the results open doors for future studies to explore how modifying metabolite levels—through diet, supplements, or other means—might reduce diabetes risk. The NRI team looks forward to building on these findings and further investigating how nutrition and metabolism intersect to shape long-term health outcomes.
Sprinkles, Jessica K., et al. “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, vol. 47, no. 11, 2024, pp. 1985-1994, https://doi.org/10.2337/dc24-1033.
