A Prospective Pilot Study Demonstrating Noninvasive Calibration-Free Glucose Measurement.

Abstract

Background: Glucose is an essential molecule in energy metabolism. Dysregulated glucose metabolism, the defining feature of diabetes, requires active monitoring and treatment to prevent significant morbidity and mortality. Current technologies for intermittent and continuous glucose measurement are invasive. Noninvasive glucose measurement would eliminate this barrier toward making glucose monitoring more accessible, extending the benefits from people living with diabetes to prediabetes and the healthy.

Methods: A novel spectroscopy-based system for measuring glucose noninvasively was used in an exploratory, prospective, single-center clinical study (NCT06272136) to develop and test a machine learning-based computational model for continuous glucose monitoring without per-subject calibration. The study design blinded the development investigators to the validation analyses.

Results: Twenty subjects were enrolled. Fifteen were used for the development set, and five in the validation set. All study participants were adults with insulin-treated diabetes and median glycated hemoglobin (HbA_1c) of 7.3% (interquartile range [IQR] = 6.7-7.7). The computational model resulted in a mean absolute relative difference (MARD) of 14.5% and 96.5% of the paired glucose data points in the A plus B zones of the Diabetes Technology Society (DTS) error grid. The correlation between the average model sensitivity by wavelength and the spectrum of glucose was 0.45 (P < .001).

Conclusions: Our findings suggest that Raman spectroscopy coupled with advanced computational methods can enable continuous, noninvasive glucose measurement without per-subject invasive calibration.