Repeated OGTT vs. continuous glucose monitoring for predicting development of stage 3 type 1 diabetes: a longitudinal analysis
OBJECTIVE Evidence for using continuous glucose monitoring (CGM) as an alternative to oral glucose tolerance tests (OGTT) 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 METHOD Thirty-four multiple autoantibody-positive first-degree relatives (FDRs) (BMI-SDS<2) were followed in a multicenter study with semi-annual 5-day CGM recordings, HbA1c, and OGTT for a median (IQR) of 3.5 (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) AUCs, Kaplan-Meier, baseline Cox models (concordance [C]) and extended Cox 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 (IQR) of 40 (20‑91) months, 17/34 FDRs (baseline median age: 16.6 years) developed stage 3. 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 (C=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 and may be more convenient for long-term clinical monitoring.