Yilin Zhu, Y F He, Shusheng Fang, Hong Chen, Jingshan Jiang, Yunxiang Ming, Song Leng
Background: To evaluate the associations of cardiometabolic indices with prediabetes progression and reversal and to identify noninvasive markers with relatively better discriminatory performance for risk stratification. Methods: We analyzed 35,525 adults (aged ≥18 years) with prediabetes from the Dalian Health Management Cohort. Associations of cardiometabolic indices with prediabetes progression and reversal were assessed using Cox proportional hazards models and restricted cubic splines (RCS). Relative discriminatory performance was compared using time-dependent receiver operating characteristic (ROC) curves, and mediation and subgroup analyses were subsequently performed. Results: Over 90,810.98 person-years, 3,125 (8.8%) participants progressed to diabetes, and 13,605 (38.8%) reverted to normoglycemia. After multivariable adjustment and standardization, triglyceride glucose-waist height ratio (TyG-WHtR) exhibited the strongest associations among the evaluated indicators (progression: HR = 2.15, 95% CI: 2.06-2.24; reversal: HR = 0.60, 95% CI: 0.59-0.62) and relatively better discriminatory performance, as supported by time-dependent ROC analysis and the calculation of C-index, NRI, and IDI. Mediation analysis indicated that gamma-glutamyl transpeptidase (GGT) and neutrophil count accounted for modest proportions of the associations with prediabetes progression (8.26 and 3.88%, respectively) and reversal (4.05 and 0.80%, respectively) through potential indirect pathways. Conclusion: Cardiometabolic indices are associated with prediabetes progression to diabetes and reversal to normoglycemia, with TyG-WHtR showing relatively better discriminatory performance in this cohort. Inflammation and oxidative stress may represent potential pathways underlying the aforementioned associations.