We appreciate the commentary by Zhao and Huang (1) on our recent work regarding the association between type 2 diabetes (T2D) risk and deviation from genetically predicted BMI (2). Their insights and suggestions underscore critical aspects that warrant further exploration in this field. We largely agree with the limitations and future research directions they have highlighted.
First, as described in our original study, we demonstrated that the association between T2D and deviations from genetically predicted BMI remained significant even after adjusting for individual BMI levels. This finding suggests that, regardless of BMI category (obese or lean), the profile of metabolic health may differ among individuals with similar BMI levels but varying genetically predicted BMI (3). Future research should investigate the extent to which metabolic heterogeneity contributes to T2D risk in individuals with such deviations.
Second, we acknowledge that factors such as dietary quality, sleep patterns, and stress levels were not explicitly included in our analysis. This limitation arose because the dietary questionnaire and sleep pattern data in UK Biobank were primarily collected via online follow-ups after baseline recruitment (4), making them challenging to integrate with our study population. Despite this, we endeavored to incorporate comprehensive socioeconomic and lifestyle factors, such as enrollment center, Townsend deprivation index, current smoking status, and physical activity, in addition to traditional risk factors and comorbidities.
Third, as noted by Zhao and Huang, the pronounced correlation between deviations from genetically predicted BMI and T2D risk in East Asian women is an intriguing finding that warrants further study. Future research should validate this observation using databases with diverse ethnic backgrounds and sex-stratified analyses. Such efforts could provide valuable insights into the underlying pathophysiological mechanisms of T2D and contribute to the advancement of personalized and precision medicine.
In conclusion, we thank Zhao and Huang for their constructive comments, which highlight the importance of further exploring metabolic health heterogeneity, detailed lifestyle factors, and ethnic and gender disparities. We believe that addressing these dimensions in future studies will enhance our understanding of T2D pathophysiology and improve prevention strategies.
Article Information
Duality of Interest. S.H.K. serves as a chief medical officer at a Seoul National University Hospital venture.
Handling Editors. The journal editors responsible for overseeing the review of the manuscript were Elizabeth Selvin and Jennifer E. Posey.
