Objective
Diabetes affects the overall metabolic health and sometimes requires a host of drugs including sodium-glucose cotransporter-2 inhibitors (SGLT2) to improve metabolic health. However sometimes these SGLT drugs, improper insulin administration, or imbalanced food intake can lead to excess metabolism of ketone leading to Diabetes Ketoacidosis (DKA) which causes more than 200,000 hospitalizations and leads to excess care cost of $5.1 Billion in the US. More and more clinicians ask their patients to monitor ketone levels in addition to blood glucose. Currently, the standard methods for at-home ketone monitoring include self-measurements using ketone test strips, either using fingerstick for blood or urine. Therefore, some blood glucose meters now are capable of measuring ketone as well (e.g. Freestyle Optium Neo) using separate strips for glucose and ketone. However, fingerpicking is painful and sporadic and hence can miss important changes in real-time ketone level leading to less patient compliance and missed early identification of DKA, leading to later complications including hospitalization and death. Similarly, urine measurements also add burden to the patient and are prone to compliance and accuracy issues. Therefore, a continuous and less painful method (like CGM) is required for automatic continuous ketone monitoring (CKM) to alarm for an impending DKA event. Although some progress has been shown in continuous ketone monitoring by others, these CKM systems are designed to measure ketone using a separate device, thus requiring the patient to wear a separate CGM and a separate CKM device. This increases cost, complexity, patient burden, and hence is a less optimal solution. The ideal solution would enable continuous measurement of ketone and glucose using a single device. Development of such a device is the objective of this proposal.
Background Rationale
Current CGMs suffer from low accuracy in the hypoglycemic region and slow response to rapid glucose variations due to device design and manufacturing challenges. Furthermore, these CGMs are limited to a single glucose sensor whereas sensing more metabolic health markers can improve the reliability of an artificial pancreas. For example, It is highly desired to include ketone sensing with glucose sensing for complete diabetes monitoring. This can decrease occurrence of Diabetes Ketoacidosis and save billions of dollars in costs and reduce adverse outcomes including hospitalizations and deaths. Owing to its semiconductor design, the IMS technology is well-suited to enable sensing multiple health markers using a single device. Moreover, the semiconductor-based design enables customization required to detect health markers other than glucose more easily as compared with other sensors that don't use a semiconductor-based sensor. Without the semiconductor technology, packaging two sensors on a small size scale requires packing many small wires into a small area, making it a complicated manufacturing and signal processing problem.
Some companies are pursuing a separate Continuous Ketone Monitor (CKM) that could be used like current leading CGM products. This would require the user to insert, wear, monitor, remove, and replace two different devices; something that could have user adoption, compliance, and cost issues. The semiconductor based design of the IMS platform enables measurement of both glucose and ketone using a single sensor. The repeatable and tightly controllable semiconductor manufacturing can enable factory calibration for longer duration as compared to current products . An 8 inch semiconductor wafer contains more than 50,000 IMS sensors , resulting in an extremely scalable and affordable manufacturing process. Additionally, since most of the signal processing is done on-chip, this simplifies the external transmitter design and decreases its size and weight. This can also help in achieving the longer wear time.
Thus, the IMS technology can enable a more accurate, faster, sensing solution with longer wear time, better user experience, and lesser cost compared to the competitor technologies.
Description of Project
Integrated Medical Sensors Inc. has been developing a novel continuous glucose monitor (CGM) using modern semiconductor and nanotechnologies. The system leverages the power of modern semiconductor technology to develop world's smallest CGM with exceptional reliability, accuracy, and speed. The system uses an electronic circuit with small metal electrodes to measure concentration of glucose in the tissue fluid just under the skin. It uses simple enzyme chemistry similar to other CGM systems to make accurate readings of glucose. The difference is the metal electrodes and the electronic circuit are made together as a single device. This brings the electronic circuit right next to the metal electrodes that are used to measure glucose. This proximity increases the quality of signal and hence reduces the inaccuracies and delays faced by other CGM devices in which the metal electrodes and the electronic circuit are further apart. Moreover, the electronic circuit is capable of measuring more than just glucose. It can be used to monitor glucose and ketone in the tissue fluid under the skin using a single user-insertable and user-removable device. This can greatly help many patients who are at-risk from high ketone levels in blood and tissue fluid at times which can lead to hospitalization or death.
Anticipated Outcome
The anticipated outcome of this program is to provide a technology prototype for our next-gen continuous diabetes monitoring (CDM) system. This product is intended to be a patient-insertable and patient-removable subdermal sensor capable of continuous glucose and ketone measurements for >14 (target 30) days. The sensor would be read using a “smart transmitter” that communicates with a smart “reader” for data analysis. The system would also interface with an insulin pump via a Bluetooth link. This can help use this information by itself or as part of an Artificial Pancreas (A). The simultaneous and continuous glucose and ketone sensing can further help identify risks like insulin line failure, and insulin deficiency. Hence, there is significant value of the work proposed here.
Relevance to T1D
Type 1 Diabetes can some time lead to imperfect ketone metabolism leading to dangerously high ketone levels in the body. This can cause an effect known diabetes ketoacidosis or DKA. This effect can be dangerous for many patients and result in more than 200,000 known hospitalization in the US every year. Therefore, continuous monitoring of ketones can help Type-1 diabetes community in early detection of DKA that can enable corrective measures to avoid serious complications. Beyond reducing the risk of Diabetes Ketoacidosis, continuous monitoring of ketone can further improve the ability to develop a safe and effective Artificial Pancreas. The IMS system is inherently fast due to fast settling time owing to better integration between a thin and flexible sensor and the surrounding tissue. This will make the proposed system well-suited for a best-in-class AP solution.