The scholarly work of Sprinkles et al. (1) has provided a treasure trove of insights into the intricate nexus between choline-derived metabolites, specifically betaine and trimethylamine N-oxide (TMAO), and the predisposition to diabetes. We appreciate the study’s valuable contributions. This letter aims to highlight areas meriting further elucidation and investigation.
First, the negative correlation between betaine and the risk of diabetes, as mentioned in the article, aligns with current mechanistic research suggesting that betaine may prevent diabetes by improving insulin resistance and reducing blood glucose levels (2). However, the ambiguity of this association in women warrants attention. Sex differences might be attributed to the impact of sex hormones on choline metabolism. It is recommended that future studies consider including measurements of sex hormone levels and explore their interplay with choline metabolite levels. Of course, beyond prevention, investigating the role of choline metabolites in the treatment of diabetes is also a field worthy of attention. For instance, exploring whether betaine could enhance the efficacy of existing diabetes medications is a line of inquiry that merits exploration.
Second, while the study has accounted for a variety of potential confounding factors, the influence of disparate dietary patterns, genetic factors, early life experiences, long-term environmental exposures, and more nuanced lifestyle elements (such as sleep patterns, stress levels, and symptoms of depression and anxiety) remains insufficiently explored (3,4). A thorough analysis of these factors is essential to discern their impact on the efficacy of the intervention.
Third, the nexus between TMAO and the susceptibility to diabetes, as delineated in the research, is notably intricate. Considering the potential influence of renal function on TMAO levels, it is imperative that forthcoming studies account for the modulatory role of renal health in the relationship between choline metabolites and the propensity for diabetes (5). Furthermore, investigating the interplay between TMAO and other metabolic pathways, including its association with markers of inflammation or indices of oxidative stress, could substantially enhance our understanding of TMAO’s role in the etiology of diabetes. Such insights may, in turn, inform the development of innovative preventative and therapeutic approaches for the management of diabetes.
In summary, the complexity of choline metabolites’ role in diabetes highlights a research imperative. Future endeavors should integrate a multidimensional perspective to illuminate diabetes management's future horizons.
Article Information
Funding. This work was supported by the Shanghai Natural Science Foundation of China (no. 23ZR1447800), Shanghai Xuhui District’s Key Medical Disciplines (no. SHXHZDXK202319), and Feng Xian District Science and Technology Commission Project (no. 20211838).
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editors responsible for overseeing the review of the manuscript were Steven E. Kahn and Csaba P. Kovesdy.
