Improved Detection of Decreased Glucose Handling Capacities via Novel Continuous Glucose Monitoring-Derived Indices: AC_Mean and AC_Var

BackgroundEfficiently detecting impaired glucose control abilities is a pivotal challenge in public health. This study assessed the utility of relatively easy-to-measure continuous glucose monitoring (CGM)-derived indices in estimating glucose handling capacities calculated from resource-intensive clamp tests. MethodsWe conducted a prospective, single-center, observational cohort study of 64 individuals without prior diabetes diagnosis. The study utilized CGM, oral glucose tolerance test, and hyperglycemic and hyperinsulinemic-euglycemic clamp tests. We validated CGM-derived indices characteristics using an independent dataset and mathematical model with simulated data. FindingsA novel CGM-derived index, AC_Var, was significantly correlated with insulin sensitivity (r = -0.31; 95% CI: -0.52 to -0.06), insulin clearance (r = -0.31; 95% CI: -0.54 to -0.06), and disposition index (DI) (r = -0.31; 95% CI: -0.52 to -0.07) calculated from clamp tests. AC_Var was also significantly correlated with insulin resistance (r = 0.48; 95% CI: 0.23 to 0.68) in an independent dataset. Multivariate analyses indicated AC_Vars contribution to predicting reduced blood glucose control abilities independent from conventional CGM-derived indices. The prediction models accuracy utilizing CGM-measured glucose standard deviation and AC_Var as input variables, with clamp-derived DI as the outcome, closely matched that of predicting clamp- from OGTT-derived DI. Mathematical simulations also underscored AC_Vars association with insulin clearance and DI. InterpretationCGM-derived indices, including AC_Var, can be useful for screening decreased blood glucose control ability. We developed a web application that calculates these indices (https://cgm-ac-mean-std.streamlit.app/). FundingThe Japan Society for the Promotion of Science KAKENHI, CREST, Japan Science and Technology Agency, and Uehara Memorial Foundation.