Generalization of a Deep Learning Model for Continuous Glucose Monitoring-Based Hypoglycemia Prediction: Algorithm Development and Validation Study.

Background: Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. Objective: The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. Methods: We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Conclusions: Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.