Early Detection of Elevated Ketone Bodies in Type 1 Diabetes Using Insulin and Glucose Dynamics Across Age Groups: Model Development Study.

Abstract

Background: Diabetic ketoacidosis represents a significant and potentially life-threatening complication of diabetes, predominantly observed in individuals with type 1 diabetes (T1D). Studies have documented suboptimal adherence to diabetes management among children and adolescents, as evidenced by deficient ketone monitoring practices.

Objective: The aim of the study was to explore the potential for prediction of elevated ketone bodies from continuous glucose monitoring (CGM) and insulin data in pediatric and adult patients with T1D using a closed-loop system.

Methods: Participants used the Dexcom G6 CGM system and the iLet Bionic Pancreas system for insulin administration for up to 13 weeks. We used supervised binary classification machine learning, incorporating feature engineering to identify elevated ketone bodies (>0.6 mmol/L). Features were derived from CGM, insulin delivery data, and self-monitoring of blood glucose to develop an extreme gradient boosting-based prediction model. A total of 259 participants aged 6-79 years with over 49,000 days of full-time monitoring were included in the study.

Results: Among the participants, 1768 ketone samples were eligible for modeling, including 383 event samples with elevated ketone bodies (≥0.6 mmol/L). Insulin, self-monitoring of blood glucose, and current glucose measurements provided discriminative information on elevated ketone bodies (receiver operating characteristic area under the curve [ROC-AUC] 0.64-0.69). The CGM-derived features exhibited stronger discrimination (ROC-AUC 0.75-0.76). Integration of all feature types resulted in an ROC-AUC estimate of 0.82 (SD 0.01) and a precision recall-AUC of 0.53 (SD 0.03).

Conclusions: CGM and insulin data present a valuable avenue for early prediction of patients at risk of elevated ketone bodies. Furthermore, our findings indicate the potential application of such predictive models in both pediatric and adult populations with T1D.