Continuous ketone monitoring: Exciting implications for clinical practice

Abstract

Diabetic ketoacidosis (DKA) is a life-threatening complication usually affecting people with type 1 diabetes (T1D) and, less commonly, people with type 2 diabetes. Early identification of ketosis is a cornerstone in DKA prevention and management. Current methods for ketone measurement by people with diabetes include capillary blood or urine testing. These approaches have limitations, including the need to carry testing strips that have a limited shelf life and a requirement for the user to initiate a test. Recent studies have shown the feasibility of continuous ketone monitoring (CKM) via interstitial fluid with a sensor inserted subcutaneously employing an enzymatic electrochemical reaction. Ketone readings can be updated every 5 minutes. In the future, one would expect that commercialized devices will incorporate alarms linked with standardized thresholds and trend arrows. Ideally, to minimize the burden on users, CKM functionality should be integrated with other devices used to implement glucose management, including continuous glucose monitors and insulin pumps. We suggest CKM provision to all at risk of DKA and recommend that the devices should be worn continuously. Those who may particularly benefit are individuals who have T1D, are pregnant, on medications such as sodium-glucose linked transporter (SGLT) inhibitors that increase DKA, people with recurrent DKA, those with T1D undertaking high intensity exercise, are socially or geographically isolated, or those on low carbohydrate diets. The provision of ketone profiles will provide important clinical insights that have previously been unavailable to people living with diabetes and their healthcare professionals.

Keywords: clinical physiology; continuous glucose monitoring; glycaemic control; type 1 diabetes.

FIGURE 1

An overview of ketone body metabolism (adapted from ³ )

FIGURE 2

Prototype PercuSense (Valencia, CA) CKM tested in a rat model with streptozotocin‐induced DKA followed by insulin rescue. Blue dots = raw CKM data. Solid blue line = filtered data. Green dots = reference capillary blood ketone measurements (Abbott Freestyle Precision Neo meter). CKM, continuous ketone monitor; DKA, diabetic ketoacidosis.

FIGURE 3

Proposed display of continuous ketone data on the same screen as continuous glucose data in an ambulatory setting. The screen on the left shows a glucose level of 6.3 mmol/L, which is stable, and a ketone level of less than 0.6 mmol/L where no values or trend arrows are displayed. The screen on the right shows a glucose level of 11.3 mmol/L that is trending downward and ketone levels of 1.3 mmol/L, which are also trending downward.

FIGURE 4

Proposed example of 14 days of continuous ketone data that have been uploaded and processed. The upper panel shows a bar graph displaying time spent in acceptable (< 1.0 mmol/L), elevated (1.0‐1.5 mmol/L), high (1.6‐3.0 mmol/L) and very high ranges (> 3.0 mmol/L). The lower panel displays a proposed ambulatory ketone profile report profiling 14 days of data according to the time of day. CKM, continuous ketone monitor.