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Repeated OGTT vs. continuous glucose monitoring for predicting development of stage 3 type 1 diabetes: a longitudinal analysis

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posted on 2025-02-04, 16:16 authored by 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 K. Gorus

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.

Funding

Medtronic provided the iPro2 devices and Enlite sensors free of charge, and the Contour Link glucometers were donated by Bayer. This study was supported by grants from the Research Foundation Flanders (FWO; project G.0868.11 and junior research fellowships for A.K.D. [1SD8122N] and A.V.D. [11D1214N]) and the Flemish government (IWT 130 138, Strategic Research Programs SRP42-Growth and SRP55 Spearhead). The Belgian Diabetes Registry received funding by the Center for Medical Innovation Flanders and by the Wetenschappelijk Fonds Willy Gepts (Scientific Fund Willy Gepts) of the UZ Brussel. W.S. holds an FWO senior clinical investigator grant (1806421N) and a BreakthroughT1D career development award (CDA-2024-1491-S-B).

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