Objective
In this proposal we will build and validate a new biosensor for the continuous measurement of ketone bodies and glucose simultaneously. Our biosensor will reduce the burden of diabetic patients to pierce their fingers to measure their ketone levels and provide a dynamic ketone monitoring.
The CGM-CKM device will integrate several components to enable continuous measurement. We will first develop a fully integrated prototype of the CGM-CKM device, and study the duration over which the measurement from our device is accurate. This will help determine the length of time a patient can wear the CGM-CKM device before it needs to be replaced. We will also determine if our device can be toxic for the wearer over the long term. Once these milestones are achieved, we will study how the CGM-CKM device performs for continuous measurement of ketones and glucose in diabetic rats and minipigs. The information that we collect from the study will inform us how to modify the device for testing with human patients. While human testing is not part of this proposal, it is the next step in the device development. We have already established a working relationship with an endocrinologist who will help us test the device and recruit patients in the future, and anticipate that patients with diabetes will be able to use the CGM-CKM device for continuous measurement in 5 years.
Background Rationale
Diabetic ketoacidosis (DKA) is a serious and fatal problem that affects people with diabetes. It occurs when the body starts breaking down fat at a rate that is much too fast. The liver processes the fat into a fuel called ketones, which causes the blood to become acidic.
DKA usually affects patients with type 1 diabetes (T1D) more than those with type 2, and it carries a high risk of death and illness, particularly increasing the risks of stroke, heart attacks and blood clotting, and the mortality rate increases with age in DKA. The number of patients who are hospitalized because of DKA is increasing. DKA, therefore, is an important disease to address to improve the wellbeing of patients with T1D. Treating DKA is also very costly for the health care system. Thus, to stop and treat DKA in a timely manner, before it causes serious illness and high health care costs, it is important to ensure that a diabetic patient is able to constantly track glucose and ketone bodies. Continuous, automatic tracking of these levels will alert patients with T1D of the risk, allowing them the opportunity to seek treatment as soon as possible to avoid further health complications.
Description of Project
Diabetes is a disease that causes serious illnesses and fatalities worldwide. Patients with type 1 diabetes (T1D) do not produce insulin, which puts them at risk of developing diabetic ketoacidosis (DKA). DKA occurs when blood sugar is high for a long time and the body starts producing high levels of blood acids known as ketone bodies. DKA is a serious condition that can lead to diabetic coma, stroke, heart attack, and even death. Thus, patients with T1D should track their levels of ketone bodies and glucose closely to prevent DKA.
While continuous glucose monitoring (CGM) devices have been developed to provide T1D patients with the ability to automatically and continuously measure their blood glucose without the need to draw blood for testing, there is no way to similarly monitor ketones: instead, ketone bodies can only be measured using blood or urine strips. Diabetic patients are encouraged to test for ketones if their glucose concentration is high, but this approach only measures a single ketone level at a single point in time, and does not provide continuous tracking. In addition, to use blood ketone meters, patients need to prick their fingers frequently to draw blood for testing, which is painful and can be challenging for children, critically ill, and elderly patients.
In this proposal, we will develop a new biosensor that is capable of continuously measuring blood ketones and glucose simultaneously. The biosensor will be easily worn by diabetic patients, without pain. Our device reaches interstitial fluid (the fluid under the skin) to measure ketones and glucose. Our device will change diabetes management by continuously monitoring both glucose and ketone bodies, in order to help prevent the risk of DKA.
Anticipated Outcome
The proposal seeks to generate a wearable device that can constantly and automatically measure the levels of ketone bodies and glucose without pain to the wearer. We anticipate that patients will be able to wear our device for at least 14 days. In this proposal, we will use diabetic animals (rats and minipigs) to test the performance of our device for the continuous measurement of ketone bodies and glucose. This will help to determine if our sensor can be applied for future human patient testing.
Relevance to T1D
This proposal is directly relevant to type 1 diabetes (T1D). Diabetic ketoacidosis (DKA) occurs when the body does not produce enough insulin, as is the case for patients with T1D. In DKA, the cells cannot use glucose as energy, so they use fat for fuel instead. Burning fat makes acids called ketones, making the blood acidic. DKA is sometimes the first sign of T1D in people who have not yet been diagnosed. It can also occur in someone who has already been diagnosed with T1D. Infection, injury, a serious illness, missing doses of insulin shots, or the stress of surgery can all lead to DKA in people with T1D. If it is not treated, DKA can cause low levels of potassium, swelling inside the brain, fluid inside the lungs, diabetic coma and even death.
Our goal is to build a wearable monitoring device that can continuously track the levels of these blood acids and glucose. Such a device will help patients with T1D to detect DKA as soon as possible and thus seek treatment for it. It is anticipated that in doing so, our device will improve the quality of life of patients with T1D.