The scholarly work of Rhee et al. (1) has provided a wealth of insights into the genetically predicted BMI and observed BMI (BMI-diff), which could reflect deviation from individual set points and may predict incident type 2 diabetes (T2D). We appreciate the study’s valuable contributions while also wishing to discuss areas for cautious interpretation and future investigation.
First, the authors demonstrate that an elevated BMI in excess of that genetically anticipated is associated with an increased risk of T2D. This finding underscores the pivotal role of obesity in the prevention and intervention strategies for metabolic disorders. However, it is suggested that future research could further explore the critical concept of metabolically healthy obesity (MHO) to enhance the depth and breadth of the investigation. Studies indicate that individuals categorized as MHO may still be at risk of latent chronic inflammation, even though their conventional metabolic profiles do not exhibit any deviations (2). Furthermore, Petersen et al. (3) provided a comprehensive comparison among individuals characterized as MHO, metabolically unhealthy obesity (MUO), and metabolically healthy lean (MHL) and highlighted the potential mechanisms that may contribute to the metabolic heterogeneity observed in obesity. Therefore, future research endeavors should consider integrating the analysis of MHO, MUO, and MHL into their analytical frameworks to provide a more holistic assessment of their influence on the risk of T2D.
Second, although the study controlled for potential confounding factors such as physical activity and smoking, key determinants known to influence an individual's BMI and risk of T2D, namely, dietary quality, sleep patterns, and stress levels, were not explicitly incorporated into the analysis. For instance, dietary quality is directly correlated with energy intake and nutritional balance, while sleep patterns are intimately linked with hormonal regulation and appetite control (4,5). Furthermore, elevated chronic stress levels impact psychological well-being, leading to weight gain and insulin resistance. These inadequately controlled confounding variables may have implications for the interpretation and extrapolation of the study's findings.
Third, the article's delineation of sex and racial disparities merits thorough investigation. The pronounced correlation between BMI differences and the risk of T2D in East Asian women warrants particular attention. What underlying sex-specific biological mechanisms might account for this association? Alternatively, could it be influenced by sociocultural determinants? It is imperative to discern these factors to inform prevention strategies that are inclusive and equitable, ensuring that they address these disparities and safeguard the health of all demographic groups effectively.
In conclusion, the work of Rhee et al. (1) offers crucial insights into the role of BMI in T2D risk, yet it highlights the need for more comprehensive research. Future studies should address the nuances of MHO, MUO, and MHL, consider broader lifestyle factors, and explore sex and racial disparities to develop prevention strategies that are truly inclusive and effective.
Article Information
Funding. This work was supported by the 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 Elizabeth Selvin and Jennifer E. Posey.
