Feasibility of Continuous Ketone Monitoring in Subcutaneous Tissue using a Ketone Sensor

Abstract

Background: The feasibility of measuring β-hydroxybutyrate in ISF using a continuous ketone monitoring (CKM) sensor using a single calibration without further adjustments over 14 days is described. Methods: A CKM sensor was developed using wired enzyme technology with β-hydroxybutyrate dehydrogenase chemistry. In vitro characterization of the sensor was performed in phosphate buffered saline at 37°C. In vivo performance was evaluated in 12 healthy participants on low carbohydrate diets, who wore 3 ketone sensors on the back of their upper arms to continuously measure ketone levels over 14 days. Reference capillary ketone measurements were performed using Precision Xtra® test strips at least 8 times a day. Results: The sensor is stable over 14 days and has a linear response over the 0-8 mM range. The operational stability of the sensor is very good with a 2.1% signal change over 14 days. The first human study of the CKM sensor demonstrated that the sensor can continuously track ketones well through the entire 14 days of wear. The performance with a single retrospective calibration of the sensor showed 82.4% of data pairs within 0.225 mM/20% and 91.4% within 0.3 mM/30% of the capillary ketone reference (presented as mM at <1.5 mM and as percentage at or above 1.5 mM). This suggests that the sensor can be used with a single calibration for the 14 days of use. Conclusions: Measuring ketones in ISF using a continuous ketone sensor is feasible. Additional studies are required to evaluate the performance in intended patient populations, including conditions of ketosis and diabetic ketoacidosis.

Continuous Ketone Monitoring Consensus Report 2021

“…Continuous ketone monitoring is a novel and evolving surveillance tool in the therapeutic portfolio that could potentially be useful for the management of T1D and other states that increase risks for ketosis, such as ketogenic diets, starvation, and sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy. A recent publication by Alva et al 1 provides important proof of concept of such a technique that could make this a clinical possibility in the near future.…”

“…In 2021 a major breakthrough in diabetes management was announced in an article by Alva et al that described the first-in-human results of a pilot study of a continuous ketone monitor (CKM). 1 The electrochemical sensor used wired enzyme technology to measure β-hydroxybutyrate (BHB), which is the major pathologic analyte in DKA. This sensor delivered good accuracy and stability, both in vitro and in vivo, for 14 days with a single retrospective calibration.…”

The Therapeutic Potential and Limitations of Ketones in Traumatic Brain Injury

“…One way to reduce the costs and improve the convivence of accurately measuring ketone levels is through developing a continuous ketone monitor, similar to that of continuous glucose monitoring systems. The first proof of concept of a continuous ketone monitor that can be placed within the subcutaneous tissue to measure ketone concentration for 14 days was recently completed ( 120 ). However, more research is needed to evaluate the performance of the device in various patient populations ( 120 ).…”

“…The first proof of concept of a continuous ketone monitor that can be placed within the subcutaneous tissue to measure ketone concentration for 14 days was recently completed ( 120 ). However, more research is needed to evaluate the performance of the device in various patient populations ( 120 ). Thus, to improve TBI treatment strategies in both intensive care and outpatient settings, it will be essential to establish technologies that can monitor ketone metabolism in accurate and minimally invasive ways.…”

The Evolution of Insulin Administration in Type 1 Diabetes

“…DH-closed loop systems discussed above show promise in mitigating early and late-onset exercise-induced hypoglycemia in T1D [157] [171] [172]. Incorporation of heart-rate detection, and lactate and ketone levels into closed-loop algorithms may also help overcome challenges associated with exercise and T1D [144] [173] [174] [175] [176].…”