The prognostic value of eGDR in prediabetes outcomes: a sex-stratified prospective cohort study

Abstract

Prediabetes is a critical phase that precedes the development of diabetes, characterized by insulin resistance as a key driver of its advancement. The estimated glucose disposal rate (eGDR) reflects insulin sensitivity, but its sex-specific prognostic value is uncertain. We analyzed a prospective cohort of 2,630 Chinese adults with prediabetes from the China Health and Retirement Longitudinal Study (CHARLS), evaluating baseline eGDR and reassessing glycemic status (diabetes, prediabetes, or normoglycemia [NFG]) after 4 years. Sex-stratified associations with diabetes progression or NFG reversion were examined using multinomial logistic regression, and lipid mediation assessed via mediation analysis. During 4-year follow-up, 1,631 remained prediabetic, 382 progressed to diabetes, and 617 reverted to NFG. Sex-stratified analyses revealed associations between eGDR and glycemic outcomes in women, but not in men. Higher eGDR in women correlated with reduced diabetes risk (RRR: 0.837; 95% CI: 0.775–0.906) and increased NFG reversion (RRR: 1.099; 95% CI: 1.018–1.187); RCS models indicated linear relationships. No associations emerged in men. Lipid profiles showed partial statistical mediation in females: HDL and TG accounted for a statistically mediated proportion of 9.48% and 4.41% for progression, respectively, while LDL and TC accounted for 5.56% and 7.22% for reversion. eGDR is associated with prediabetes outcomes in a sex-specific manner, evident only in women and partially mediated by lipids. These findings suggest that eGDR may have sex-related prognostic value, with lipid parameters potentially playing a role in the statistical mediation of these associations. However, given the borderline interaction P value ( P  = 0.071), these findings should be interpreted cautiously and warrant further validation.