Repeated OGTT Versus Continuous Glucose Monitoring for Predicting Development of Stage 3 Type 1 Diabetes: A Longitudinal Analysis
Aster K. Desouter, Bart Keymeulen, Ursule Van de Velde, Annelien Van Dalem, Bruno Lapauw, Christophe De Block, Pieter Gillard, Nicole Seret, Eric V. Balti, Elena R. Van Vooren, Willem Staels, Sara Van Aken, Marieke den Brinker, Sylvia Depoorter, Joke Marlier, Hasan Kahya, Frans Gorus
Abstract
OBJECTIVE: Evidence for using continuous glucose monitoring (CGM) as an alternative to oral glucose tolerance tests (OGTTs) in presymptomatic type 1 diabetes is primarily cross-sectional. We used longitudinal data to compare the diagnostic performance of repeated CGM, HbA1c, and OGTT metrics to predict progression to stage 3 type 1 diabetes. RESEARCH DESIGN AND METHODS: Thirty-four multiple autoantibody-positive first-degree relatives (FDRs) (BMI SD score [SDS] <2) were followed in a multicenter study with semiannual 5-day CGM recordings, HbA1c, and OGTT for a median of 3.5 (interquartile range [IQR] 2.0-7.5) years. Longitudinal patterns were compared based on progression status. Prediction of rapid (<3 years) and overall progression to stage 3 was assessed using receiver operating characteristic (ROC) areas under the curve (AUCs), Kaplan-Meier method, baseline Cox proportional hazards models (concordance), and extended Cox proportional hazards models with time-varying covariates in multiple record data (n = 197 OGTTs and concomitant CGM recordings), adjusted for intraindividual correlations (corrected Akaike information criterion [AICc]). RESULTS: After a median of 40 (IQR 20-91) months, 17 of 34 FDRs (baseline median age 16.6 years) developed stage 3 type 1 diabetes. CGM metrics increased close to onset, paralleling changes in OGTT, both with substantial intra- and interindividual variability. Cross-sectionally, the best OGTT and CGM metrics similarly predicted rapid (ROC AUC = 0.86-0.92) and overall progression (concordance = 0.73-0.78). In longitudinal models, OGTT-derived AUC glucose (AICc = 71) outperformed the best CGM metric (AICc = 75) and HbA1c (AICc = 80) (all P < 0.001). HbA1c complemented repeated CGM metrics (AICc = 68), though OGTT-based multivariable models remained superior (AICc = 59). CONCLUSIONS: In longitudinal models, repeated CGM and HbA1c were nearly as effective as OGTT in predicting stage 3 type 1 diabetes and may be more convenient for long-term clinical monitoring.