Avoiding DKA With Continuous Ketone Monitoring
Might there be a way to detect and prevent the serious complication of diabetic ketoacidosis (DKA) before it happens?
As people with diabetes may know, diabetic ketoacidosis (DKA) is a short-term complication of diabetes that can happen when the body does not have enough insulin. When the body does not have enough insulin, the body can break down fats for energy, which produces ketones. The body can handle the breakdown of a small amount of ketones, but not large amounts which can make the blood acidic. During diabetic ketocidosis—which is very different from ketosis—high levels of ketones, even for a few hours, can cause serious illness affecting the brain, other organs, and can be potentially life-threatening.
One of the key topics discussed at the Advanced Technologies and Treatments for Diabetes (ATTD) 2023 conference in Berlin was the need for continuous ketone monitoring (CKM), and concerns about the lack of awareness about when and how to measure ketones among people with diabetes.
“There is great interest in the clinical and scientific community about the future of CKM technology,” said Dr. Rodica Busui, associate director of clinical research at the Caswell Diabetes Institute at the University of Michigan.
According to Dr. David O’Neal, director and founder of the Diabetes Technology Research Group at the University of Melbourne, Australia, a significant portion of people with diabetes do not have the equipment to test ketone levels. In a study of 205 people with diabetes conducted by his group in several Melbourne clinics, more than 30% of people with type 1 did not own a ketone test kit, and many of those who did were not testing regularly or did not know when to do so.
O’Neal said that continuous ketone sensing could be especially useful for people with diabetes:
With recurring DKA
On very low carb/weight loss diets
On ‘sick days’
Taking medications like SGLT-2 inhibitors that can increase DKA risk
O’Neal described ketone monitoring, and an ideal CKM device, to be like an airbag. “You might never need it, but it could save your life,” he said.
He continued, “It should be accurate at low ranges, durable and integrated with other sensors, and should not be an additional cost burden to the user.” His group has suggested that for the technology to have a widespread effect on people with diabetes, glucose and ketones should be measured by the same sensor. Ketone sensing would run in the background, alerting the user at a level that allows them to seek medical advice, adjust insulin, and possibly prevent a visit to the hospital.
DKA and SGLT-2 Inhibitors
A relatively new class of glucose-lowering medications called SGLT-2 inhibitors have also been shown to protect against kidney disease and heart failure in people with type 2 diabetes. While many people with type 1 diabetes – who face similar risks for these complications – could potentially benefit from these drugs, studies have shown that SGLT-2 inhibitors increase the risk of DKA—even DKA without high blood sugars.
Some people with T1D have been prescribed these drugs “off-label” by their health care providers, but they have not been approved by the FDA for type 1 diabetes because of the risk of DKA. A combined continuous glucose and ketone monitor offers a potential solution to this issue. If a sensor could detect increasing ketone levels in time for people to address it on their own and avoid DKA, more people with type 1 could safely take SGLT-2 inhibitors to protect against kidney disease and heart failure.
“DKA exists with SGLT-2 inhibitors, but we are now in a position to apply strategies and develop new technologies to mitigate this risk so that we can start getting more information on reducing risk for [kidney and heart complications] in all people with diabetes,” Busui said.
Where are we with continuous ketone monitoring?
Many companies are looking to develop a sensor that monitors glucose, ketones, and other molecules in the body all at once; the furthest along in development is a combined CGM-CKM by Abbott.
Shridhara Alva, divisional vice president, clinical affairs at Abbott Diabetes Care, discussed some additional details about the technology.
The first human study, which involved a Freestyle Libre 2 combined continuous glucose and ketone monitor, included 12 people without diabetes on a low-carb diet and showed that the sensor was able to accurately track ketone levels, as compared to measurements done with test strips.
“We can measure [ketones] with a good correlation to [reference] ketone values, measurement is stable over the 14-day wear time, and it can be factory calibrated effectively,” Alva said. “The sensor also responds quickly to changing ketone levels, as would be needed to detect an oncoming episode of DKA.”
More data and larger studies are needed to test the new technology. However, the device has received FDA breakthrough designation status, meaning that the FDA will accelerate its path toward future approval. The device is currently in smaller trials, with plans for additional trials later in 2023.