Discussion
To the best of our knowledge, this is the initial large-scale cohort analysis in the UK to investigate the link between BRI and the development of T2D, incorporating the impact of longitudinal BRI changes. Our study identified significant associations between BRI and new-onset T2D. A J-shaped non-linear correlation of BRI and T2D risk was detected through RCS modeling, with an inflection point observed at a BRI of 3.93. Specifically, individuals with a grade increase in the low baseline BRI group demonstrated a raised risk of developing T2D in comparison with those in the stable-low BRI groups. Statistically significant associations were also observed between both the grade-decreasing and grade-increasing BRI and the risk of T2D in the middle baseline BRI population, relative to the stable-middle BRI group. Furthermore, individuals with high baseline BRI in the grade-decreasing group corresponded with a reduced risk of T2D relative to the stable-high BRI group, indicating their potential protective role. Using the RCS model, a non-linear connection was discovered between the AARC of BRI and the risk of T2D. When the AARC of BRI was less than zero, it was negatively associated with T2D risk, whereas a positive correlation was found when the AARC of BRI exceeded zero, suggesting an increased risk of T2D. Specifically, an AARC below −11.37% suggested to be strongly negatively correlated with risk of T2D, while an AARC exceeding 25.70% showed a significantly strong positive association with T2D risk. The results of the sensitivity analysis were generally consistent with the main analysis. Notably, in the population with three or more BRI measurements, the sensitivity analysis revealed that each tertile increase in the SD of BRI was associated with an 88% increase in the risk of T2D. This suggests that the main analysis, which showed a significant association between BRI change and T2D, remains valid even when accounting for the variability in BRI over time.
Previous studies have provided supporting evidence for the connection between the BRI and the risk of diabetes, particularly T2D. Data from 15 310 subjects of health examination programs in a retrospective study at Murakami Memorial Hospital revealed that elevated baseline BRI was an independent risk marker for T2D. Furthermore, BRI exhibited a sex-specific non-linear association with T2D risk, with a J-shaped relationship noted in males and inflection points at 3.146 for males and 4.137 for females.29 Analogously, a prospective study based on 10 785 subjects from the China Health and Retirement Longitudinal Study (CHARLS) identified a notable positive link between elevated BRI and greater risk of T2D.30 Moreover, the analysis indicated a non-linear association, showing an inflection at a BRI of 3.96, which aligns closely with our findings. Qiu et al reported a significant non-linear positive association was found between BRI and the occurrence of diabetes and pre-diabetes in US adults.31 Based on a cross-sectional analysis of 11 980 adults aged 20 years and older from the National Health and Nutrition Examination Survey, the results indicate that BRI could be an effective predictor for diabetes and pre-diabetes. An additional cross-sectional investigation carried out in rural northeastern China, which included 5253 men and 6092 women, reported that BRI displayed potential as an alternative anthropometric measure for assessing diabetes risk.32 Given the limited sample sizes of previous studies, our findings further support the correlation between BRI and T2D risk in a substantially larger population-based cohort.
However, to our knowledge, there was limited research on the long-term changes of BRI changes and their association with T2D, although studies on other common chronic diseases had been conducted. In recent years, a prospective study based on the Tehran Lipid and Glucose Study cohort investigated 1681 initially healthy women, among whom 320 developed diabetes during follow-up.33 The findings revealed that higher trajectories of BRI showed a significant positive correlation with diabetes risk compared with lower BRI trajectories. Furthermore, two studies from the Kailuan Cohort found that higher BRI trajectories (moderate stable, moderate-high stable, and high stable) were associated with increased CVD risk34 and that a high-stable BRI trajectory was significantly linked to cancer incidence.35 These findings were highly consistent with those from a study involving 9935 participants from the CHARLS, which also found that a higher BRI trajectory was related to an increased likelihood of CVD, suggesting that BRI had potential as a predictive marker for CVD incidence.36 These findings highlighted the importance of dynamic changes in BRI when assessing chronic disease risk. Furthermore, our more granular classification captures trajectories, offering improved risk stratification beyond traditional stable-group categorizations.
Although the underlying pathophysiological mechanisms linking BRI to T2D development require additional research, the observed association may be partially explained by the following potential biological mechanisms. Middle or high BRI levels typically reflect greater accumulation of visceral fat, which is metabolically active and releases pro-inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, promoting chronic low-grade inflammation. This inflammatory condition impairs insulin signaling pathways, leading to increased insulin resistance.37 38 Indeed, visceral adipose tissue is fundamental to the development of insulin resistance.39 Furthermore, excess visceral fat can directly impair insulin sensitivity in the liver, skeletal muscle, and adipose tissue, all of which are critical target organs for glucose metabolism, causing worsened insulin resistance and a higher risk of T2D.40 Nonetheless, additional research is required to clarify these mechanisms and establish causality.
Our study not only investigated the association between baseline BRI and the risk of T2D but also extended the analysis to measure the correlation between long-term BRI change and T2D incidence. By incorporating repeated BRI measurements over time, we were able to identify subgroups characterized by distinct longitudinal changes. Importantly, BRI serves as a simple yet robust anthropometric indicator that better reflects visceral fat accumulation and cardiometabolic risk as opposed to conventional metrics such as BMI and WC. Continuous monitoring of BRI may facilitate early identification of individuals at elevated risk, enabling timely and targeted interventions. Additionally, our findings highlight the public health value of sustained visceral fat reduction through long-term lifestyle modifications to mitigate the growing burden of T2D.
Nonetheless, several limitations should be noted. First, the study population is composed exclusively of European individuals, which may restrict the applicability of our results to other ethnic populations. Second, the relatively short follow-up duration in the BRI change analysis may have led to an underestimation of incident cases and attenuated the observed associations. Third, due to data limitations, changes in BRI were assessed using only two time points, and the timing of the last BRI measurement varied considerably across individuals. However, the timing of the last BRI measurement has already been accounted for in the quantitative assessment of change using the AARC metric. This approach helps to mitigate potential bias arising from variations in follow-up duration across individuals and enhances the accuracy of longitudinal evaluations. Furthermore, covariates were adjusted only at baseline due to incomplete follow-up data, possibly overlooking time-varying confounders. Therefore, further studies with extended follow-up periods, more repeated assessments, and more diverse ethnic groups are necessary to validate and extend these findings.
In conclusion, this research offers a novel understanding of the link between BRI and T2D. We found that a higher BRI at baseline was strongly associated with an increased risk of developing T2D, with a significant non-linear relationship observed. Furthermore, long-term increases in BRI change were associated with a higher risk of T2D, whereas decreases were linked to a lower risk. These findings point to the value of both the level and longitudinal pattern of BRI as predictive indicators of T2D risk. Continuous monitoring of BRI changes over time could aid in the early detection of individuals at elevated risk and inform targeted interventions aimed at reducing BRI to help prevent the onset of T2D.
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