Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning
Eslam Montaser, Marc D. Breton, Sue A. Brown, Mark D. DeBoer, Boris Kovatchev, Leon S. Farhy
Abstract
Background: Predicting the risk for type 1 diabetes (T1D) is a significant challenge. We use a 1-week continuous glucose monitoring (CGM) home test to characterize differences in glycemia in at-risk healthy individuals based on autoantibody presence and develop a machine-learning technology for CGM-based islet autoantibody classification. Methods: Sixty healthy relatives of people with T1D with mean ± standard deviation age of 23.7 ± 10.7 years, HbA1c of 5.3% ± 0.3%, and body mass index of 23.8 ± 5.6 kg/m 2 with zero ( n = 21), one ( n = 18), and ≥2 ( n = 21) autoantibodies were enrolled in an National Institutes of Health TrialNet ancillary study. Participants wore a CGM for a week and consumed three standardized liquid mixed meals (SLMM) instead of three breakfasts. Glycemic outcomes were computed from weekly, overnight (12:00–06:00), and post-SLMM CGM traces, compared across groups, and used in four supervised machine-learning autoantibody status classifiers. Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. Results: Among all computed glycemia metrics, only three were different across the autoantibodies groups: percent time >180 mg/dL (T180) weekly ( P = 0.04), overnight CGM incremental AUC ( P = 0.005), and T180 for 75 min post-SLMM CGM traces ( P = 0.004). Once overnight and post-SLMM features are incorporated in machine-learning classifiers, a linear support vector machine model achieved the best performance of classifying autoantibody positive versus autoantibody negative participants with AUC-ROC ≥0.81. Conclusion: A new technology combining machine learning with a potentially self-administered 1-week CGM home test can help improve T1D risk detection without the need to visit a hospital or use a medical laboratory. Trial registration: ClinicalTrials.gov registration no. NCT02663661.