Non-Invasive Blood Glucose Estimation from Exhaled Breath: Patient-Level Validation of a Compact Electronic Nose Approach

Non-invasive blood glucose estimation from exhaled breath has been proposed as a painless alternative to repeated capillary measurements; however, performance evaluation remains challenging in small-sample settings. This study investigates the estimation of blood glucose from human breath using volatile organic compound (VOC) signals acquired with an electronic nose. Responses from three metal-oxide sensor channels sensitive to CO, alcohol, and acetone were collected from 58 individuals, with one measurement per subject, and analyzed using strictly patient-level five-fold cross-validation, in which test folds comprised only real subjects. Two experimental factors were examined. First, model performance was evaluated with and without an additional interpretable alcohol–acetone log-ratio capturing relative variation between compounds. Second, model training was performed using either real data only or fold-wise tabular synthetic augmentation generated via a Gaussian copula fitted exclusively on training subjects, while evaluation remained strictly real-only. Under real-only training, classical machine learning models achieved the lowest prediction errors (approximately 6–7 mg/dL), whereas under synthetic augmentation FTTransformer was the best-performing deep learning model. This findings should be understood as a constrained proof-of-concept analysis rather than as evidence of diagnostic capability or clinical readiness.