BackgroundAlterations in glucose metabolism, especially the postprandial glucose response (PPGR), are crucial contributors to metabolic dysfunction, which underlies the pathogenesis of metabolic syndrome (MetSyn). Personalized low-glycemic diets (PLGD) have shown promise in reducing postprandial glucose spikes. However, current methods such as invasive continuous glucose monitoring (CGM) or multi-omics data integration to assess PPGR come with limitations, including cost and invasiveness, hindering widespread adoption in primary disease prevention. Our aim is to assess machine-learning algorithms for predicting individual PPGR using non-invasive wearable data, thereby circumventing the limitations associated with existing approaches. By identifying the most accurate model, we seek to provide a more accessible and efficient method for managing glucose metabolism. MethodsThis data-driven analysis utilized the experimental dataset from the SENSE (”Systemische Ernährungsmedizin”) study. Healthy participants used an Empatica E4 wristband and Abbott Freestyle Libre 3 CGM for ten days. Blood volume pulse (BVP), electrodermal activity (EDA), heart rate (HR), skin temperature (TEMP), and the corresponding CGM values were measured. Subsequently, four data-driven deep learning (DL) model-convolutional neural network (CNN), lightweight transformer (LTF), long short-term memory with attention (LSTM-A), and Bi-directional LSTM (BiLSTM)-were implemented and compared to determine the potential of DL in predicting interstitial glucose levels without involving food and activity logs. ResultsThe proposed BiLSTM achieved the best interstitial glucose prediction performance, with an average root mean squared error (RMSE) of 13.42 mg/dL, an average mean absolute percentage error (MAPE) of 0.12, and only 3.01% values falling within area D in Clarke error grid analysis (CEGA), incorporating the leave-one-out cross-validation (LOOCV) strategy for a five-minute prediction horizon. ConclusionThe findings of this study may demonstrate the feasibility of transferring knowledge gained from invasive glucose monitoring devices to non-invasive approaches. Furthermore, it emphasizes the promising prospects of combining deep learning with wearable technologies to predict glucose levels in healthy individuals.