Feasibility of Continuous Ketone Monitoring in Subcutaneous Tissue Using a Ketone Sensor.

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Metabolic Monitoring

Background:

• Continuous monitoring of β-hydroxybutyrate in interstitial fluid (ISF) is crucial for metabolic health management.
• Existing methods for ketone body measurement have limitations in continuous, real-time assessment.

Purpose of the Study:

• To evaluate the feasibility and performance of a novel continuous ketone monitoring (CKM) sensor for measuring β-hydroxybutyrate in ISF.
• To assess the sensor's stability and accuracy over a 14-day period with a single calibration.

Main Methods:

• Development of a CKM sensor utilizing wired enzyme technology and β-hydroxybutyrate dehydrogenase chemistry.
• In vitro characterization in phosphate-buffered saline at 37°C.
• In vivo evaluation in 12 healthy participants on low-carbohydrate diets over 14 days, with reference capillary ketone measurements.

Main Results:

• The CKM sensor exhibited stability over 14 days with a linear response (0-8 mM) and minimal signal change (2.1%).
• The sensor accurately tracked ketone levels continuously throughout the 14-day wear period.
• A single retrospective calibration achieved high agreement with capillary ketone references (82.4% within 0.225 mM/20% and 91.4% within 0.3 mM/30%).

Conclusions:

• Continuous measurement of β-hydroxybutyrate in ISF using the developed CKM sensor is feasible.
• The sensor demonstrates potential for reliable, long-term ketone monitoring with a single calibration.
• Further studies are needed to validate performance in patient populations experiencing ketosis or diabetic ketoacidosis.