Welcome to the ATTD 2023 Interactive Program
IS018 - Clinical need for continuous ketone monitoring integrated into CGM devices (i.e. CGM-CKM) (ID 210)
Abstract
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In people with type 1 diabetes, diabetic ketoacidosis (DKA) is a medical emergency and a major threat to life. While a failure in insulin delivery would also be signalled by increasing glucose levels, there are other causes of elevated glucose levels which are less likely to be associated with ketosis e.g. carbohydrate ingestion covered by an inadequate bolus, or emotional stress. In addition, DKA can also present without hyperglycaemia. Therefore, ketone levels should be checked in the face of significantly elevated glucose levels or if the person has nausea or vomiting. The current standard of care is measurement of capillary blood ketones using a ketone-capable meter. However, some people with type 1 diabetes may not check their ketones in a timely manner as not all meters have a ketone measuring function, and many people do not have in date ketone testing strips with them.
Continuous glucose monitors are now the standard of care for glucose monitoring in people with type 1 diabetes in advantaged countries. These devices currently sense a single analyte only (interstitial glucose). Evidence indicates that interstitial ketone levels closely mirror those in blood. Incorporating a ketone sensor as part of a multianalyte platform which also senses glucose would overcome some of the limitations associated with our current approach to the early detection and management of ketosis. An ideal device would not increase the user’s physical, emotional, or financial burden. The ketone component of the multianalyte sensor should act analogously to a car’s airbag, sitting unobtrusively in the background for most of the time, and becoming evident and lifesaving under those (hopefully exceptional) circumstances when needed. A continuous glucose/ ketone sensor would be relevant to the general type 1 diabetes population and of particular importance for those with recurrent DKA; during an acute illness; those who are pregnant; those on an SGLT2 inhibitor; those on a low carbohydrate diet; or those undertaking high intensity exercise.
IS019 - SGLT inhibitors in T1D: DKA risk and DKA risk mitigation strategies, especially CGM-CKM, to enable therapy use for heart and kidney health (ID 211)
Abstract
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Despite continous progress in the development and implementation of diabetes technologies (including automated insulin delivery systmes) into the clinical care for people with type 1 diabetes (T1D), only 20% T1D individuals meet the evidence-based A1c target shown to prevent chronic complications such as renal and cardiovascular disease (CVD). Additionally, a solley intensive insulin management regimen is associated with residual challenges such as overweight/ obesity, high disease self-management burden, substantial diabetes-related emotional distress, fear of hypoglycemia. Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) in the USA and developed world despite improvements in glycemia management and the use of renin-angiotensin system blockade, with incidence rates of 30-40% in T1D. Also, heart failure has emerged as the most prevalent CVD complication in people with T1D, while DKD markedly increases the risk of CVD and heart failure, leading causes of increased mortality in T1D. For people with type 2 diabetes, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emmerged to effectively prevent CVD and DKD progression and associated severe outcomes including death. Whether similar results can be achieved in T1D remains unknown because traditionally people with T1D were excluded from the larger CVD and CKD outcome trials. Add-on to insulin SGLTi therapy was shown to associate with significant glycemic, weight loss, and blood pressure benefits in several randomized clinical trials , and have been approved in Europe and in Japan for use in T1D. However, there are concerns about a causally increase in risk of diabetic ketoacidosis (DKA) with SGLT2i therapy in T1D. Background risk of DKA in the contemporary T1D population remains high, estimated at 5-7%. Furthermore, DKA is substantially more common in the underprivileged (lower socioeconomic class, certain ethnicities), among those struggling the most with self-management, younger age, and higher A1c. SGLTi is designated a component cause as it is neither necessary for the occurrence of DKA (the outcome is known to occur from other factors in the absence of SGLTi), nor sufficient (the outcome requires another precipitating factor in addition to the SGLTi such as illness, infection, starvation, or insulin pump malfunction). Mitigation strategies created by expert clinician and researcher panels have been published, though their implementation in clinical practice and their acceptatbility to patients and healthcare providers is not known. Data on the prevalence and risk of DKA in contemporary populations with T1D, the risk with SGLT2i as well optimal mitigation strategies will be dicussed.IS020 - Pre-clinical development of CGM-CKM (ID 212)
Abstract
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The unmet need for ketone monitoring in the diabetic population is underscored by the rising incidence of Diabetic Ketoacidosis (DKA). Current solutions for ketone monitoring are expensive and cumbersome, mostly involving serial measurements of capillary blood. These solutions are insufficient for real-time monitoring of ketone levels, which is required for reducing DKA incidence. Continuous Ketone Monitoring (CKM) wearable patches are under development by several groups, employing different approaches to measure levels of the most prominent ketone - beta-hydroxybutyrate (BHB) - in the interstitial fluid (ISF). Most of these approaches rely on the enzyme BHB-dehydrogenase to specifically oxidize BHB to pyruvate while generating the co-factor NADH in the process, which is then electrochemically sensed. QuLab Medical has developed a novel minimally-invasive intradermal patch platform for continuously monitoring multiple metabolites in parallel. We are in the process of developing a novel non-enzymatic sensor for BHB sensing. Combining this sensor with a CGM in a single patch device is expected to greatly benefit T1D patients, providing them with multiple additional treatment options and empowering them to better monitor their condition and improve their overall health and well-being.
IS021 - Feasibility and performance of a continuous ketone monitoring sensor (ID 213)
Abstract
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Current methods of ketone measurement using urine or blood ketones do not indicate the onset of ketosis or ketoacidosis, rather confirm if it is already in progress. In the case of diabetes ketoacidosis (DKA), alerting the patient about an impending DKA would reduce the complications of DKA, including hospitalization or even prevent it.Feasibility of a subcutaneous continuous ketone monitoring (CKM) sensor was demonstrated using β-hydroxybutyrate dehydrogenase enzyme with a proprietary mediation chemistry in a FreeStyle Libre 2 sensor form factor. The in vitro performance of the sensor has been demonstrated up to 8 mmol/L, showing that the sensor responds linearly to the change in the concentration of ketone and with minimal variation between sensors. The first human study with participants on low carbohydrate diet demonstrated that subcutaneous ketone can be measured with these sensors, which tracks the capillary ketone levels over a 14-day period with a single retrospective calibration. The ketone levels generated with low carbohydrate diet were limited to 2mmol/L.
For the CKM sensor to be viable, the sensor needs factory calibration, as the fingerstick calibration is impractical. Performance of a factory calibrated sensor in the FreeStyle Libre 2 form factor was evaluated in a clinical setting where the study participants (without diabetes) consumed exogenous ketone to generate elevated ketone levels. The sensor results were compared to venous blood ketone using Precision Xtra ketone test strips. The sensor responded quicky to the changing ketone concentrations and the lag time was about 4 minutes. The mean absolute difference between the sensor and the reference results was 0.3 mmol/L.
The integrated continuous glucose – ketone monitoring will leverage the FreeStyle Libre 3 form factor. This dual analyte sensor system is designed to continuously monitor glucose and ketones levels every minute, in one sensor.
Funding: This study was funded by Abbott Diabetes Care, Alameda, CA
Q&A (ID 753)