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

Background Efficiently 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. Methods We 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. Findings A 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\_Var’s contribution to predicting reduced blood glucose control abilities independent from conventional CGM-derived indices. The prediction model’s 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\_Var’s association with insulin clearance and DI. Interpretation CGM-derived indices, including AC_Var, can be useful for screening decreased blood glucose control ability. We developed a web application that calculates these indices (). Funding The Japan Society for the Promotion of Science KAKENHI, CREST, Japan Science and Technology Agency, and Uehara Memorial Foundation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (JP21H04759), CREST, the Japan Science and Technology Agency (JST) (JPMJCR2123), and The Uehara Memorial Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted in accordance with the Declaration of Helsinki and its amendments, and was approved by the ethics committee of Kobe University Hospital (Approval No. 1834; Kobe, Japan). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The CGM data that support the findings of this study are available from the GitHub repository (https://github.com/HikaruSugimoto/CGM\_AC). The code that calculates AC\_Mean and AC\_Var is also available from the repository (https://github.com/HikaruSugimoto/CGM\_AC) and the web application (https://cgm-ac-mean-std.streamlit.app/).