Modeling risk of hypoglycemia during and following physical activity in people with type 1 diabetes using explainable mixed-effects machine learning.

BACKGROUND: Physical activity (PA) can cause increased hypoglycemia (glucose <70 mg/dL) risk in people with type 1 diabetes (T1D). We modeled the probability of hypoglycemia during and up to 24 h following PA and identified key factors associated with hypoglycemia risk. METHODS: We leveraged a free-living dataset from Tidepool comprised of glucose measurements, insulin doses, and PA data from 50 individuals with T1D (6448 sessions) for training and validating machine learning models. We also used data from the T1Dexi pilot study that contains glucose management and PA data from 20 individuals with T1D (139 session) for assessing the accuracy of the best performing model on an independent test dataset. We used mixed-effects logistic regression (MELR) and mixed-effects random forest (MERF) to model hypoglycemia risk around PA. We identified risk factors associated with hypoglycemia using odds ratio and partial dependence analysis for the MELR and MERF models, respectively. Prediction accuracy was measured using the area under the receiver operating characteristic curve (AUROC). RESULTS: The analysis identified risk factors significantly associated with hypoglycemia during and following PA in both MELR and MERF models including glucose and body exposure to insulin at the start of PA, low blood glucose index 24 h prior to PA, and PA intensity and timing. Both models showed overall hypoglycemia risk peaking 1 h after PA and again 5-10 h after PA, which is consistent with the hypoglycemia risk pattern observed in the training dataset. Time following PA impacted hypoglycemia risk differently across different PA types. Accuracy of hypoglycemia prediction using the fixed effects of the MERF model was highest when predicting hypoglycemia during the first hour following the start of PA (AUROCVALIDATION = 0.83 and AUROCTESTING = 0.86) and decreased when predicting hypoglycemia in the 24 h after PA (AUROCVALIDATION = 0.66 and AUROCTESTING = 0.68). CONCLUSION: Hypoglycemia risk after the start of PA can be modeled using mixed-effects machine learning to identify key risk factors that may be used within decision support and insulin delivery systems. We published the population-level MERF model online for others to use.

Combining uncertainty-aware predictive modeling and a bedtime Smart Snack intervention to prevent nocturnal hypoglycemia in people with type 1 diabetes on multiple daily injections.

OBJECTIVE: Nocturnal hypoglycemia is a known challenge for people with type 1 diabetes, especially for physically active individuals or those on multiple daily injections. We developed an evidential neural network (ENN) to predict at bedtime the probability and timing of nocturnal hypoglycemia (0-4 vs 4-8 h after bedtime) based on several glucose metrics and physical activity patterns. We utilized these predictions in silico to prescribe bedtime carbohydrates with a Smart Snack intervention specific to the predicted minimum nocturnal glucose and timing of nocturnal hypoglycemia. MATERIALS AND METHODS: We leveraged free-living datasets collected from 366 individuals from the T1DEXI Study and Glooko. Inputs to the ENN used to model nocturnal hypoglycemia were derived from demographic information, continuous glucose monitoring, and physical activity data. We assessed the accuracy of the ENN using area under the receiver operating curve, and the clinical impact of the Smart Snack intervention through simulations. RESULTS: The ENN achieved an area under the receiver operating curve of 0.80 and 0.71 to predict nocturnal hypoglycemic events during 0-4 and 4-8 h after bedtime, respectively, outperforming all evaluated baseline methods. Use of the Smart Snack intervention reduced probability of nocturnal hypoglycemia from 23.9 ± 14.1% to 14.0 ± 13.3% and duration from 7.4 ± 7.0% to 2.4 ± 3.3% in silico. DISCUSSION: Our findings indicate that the ENN-based Smart Snack intervention has the potential to significantly reduce the frequency and duration of nocturnal hypoglycemic events. CONCLUSION: A decision support system that combines prediction of minimum nocturnal glucose and proactive recommendations for bedtime carbohydrate intake might effectively prevent nocturnal hypoglycemia and reduce the burden of glycemic self-management.