Objective
Continuous Ketone Monitors (CKM) are a new technology that provide automatic alerts when ketones are elevated. This technology has the potential to substantially reduce risk for diabetic ketoacidosis (DKA). However, to realize this potential, patients will need guidance on how to translate the ketone data into action to prevent DKA. In this project we will develop and evaluate a digital health system – with on-demand treatment guidance via a smartphone app – to support the use of continuous ketone monitoring (CKM) in diabetes care. To achieve this goal, we will collaborate with a user-centered designer to develop customized patient educational and clinical guidance tools to support the effective use of CKM. The design process will include direct evaluation of the usability of the dosing decision-making tools in people with diabetes, including individuals with limited health literacy. We will conduct clinical trials to evaluate the efficacy of CKM coupled with this smartphone-delivered treatment guidance to reduce the risk for DKA. Finally, we will explore patient experience using CKM and the treatment guidance tools – using patient-reported outcome surveys, ecological momentary assessment, and individual interviews – and will apply the learnings from this investigation to optimize the tools for future dissemination. Our goal is to increase the likelihood that all patients with T1D, including individuals who do not receive care from expert diabetes clinicians, will be able to use CKM effectively to prevent DKA.
Background Rationale
Over the past decade, improvements in the care and health outcomes for individuals living with T1D has been notable. However, these improvements in treatments and technologies have not significantly reduced the risk individuals face for DKA. In part, this remaining risk for DKA is a result of the current methods available for ketone testing (fingerstick blood monitors or urine strips). Data shows that following clinical guidelines for ketone monitoring is poor. In fact, survey data from the T1D exchange clinic registry indicates that adults are generally not attentive to clinical guidelines for ketone monitoring, with only 9% of adults aged over 26 years self-testing for ketones when nauseated and/or vomiting. In contrast, almost 90% of children with T1D aged less than 6 years will have ketones checked by their caregivers in the context of these symptoms. Even when patients are in possession of urine ketone strips utilization rates are low. In a multicenter study from Germany 21% of adults presenting with DKA possessed ketone strips but only 6% performed ketone testing. In the subset of this cohort with recurrent DKA 85% had ketone strips, yet only 7% checked ketones. The development of CKM systems offers a fundamental shift in the opportunities to prevent DKA, improve health outcomes, and save health care dollars.
However, the potential challenges with use of this technology are not yet known. In addition, since DKA is fairly infrequent, patients rarely remember what they need to do when ketones levels are increased. While some diabetes self-care tasks (such as the treatment of hypoglycemia) become automatic from repeated episodes and reinforcement learning, less common practices related to ketone testing (such as “sick-day” diabetes management and trouble-shooting insulin pump non-delivery) do not become ingrained behaviors. Moreover, with the exception of clinical trials, few patients have 24/7 access to expert guidance during these low-frequency emergency situations. In this project we will develop customized patient educational and clinical guidance tools to support the effective use of CKM and reduce the risk for DKA.
Description of Project
Despite recent advances in the treatment of type 1 diabetes (T1D), interventions to prevent diabetic ketoacidosis (DKA) remain a major gap in diabetes care. Current methods for ketone testing with fingerstick blood monitors or urine strips require patient engagement, and adherence is poor. Continuous Ketone Monitors (CKM) are a new technology that provide automatic alerts when ketones are elevated. This technology has the potential to substantially reduce the risk for DKA.
In this project we will investigate and address key potential gaps and barriers to the widespread and effective use of CKM. Specifically:
- To realize the potential of CKM as a tool to prevent DKA, the introduction of this technology will need to coupled with customized diabetes self-management guidance to ensure that patients can effectively act on the ketone data to prevent DKA. To achieve this goal, in Specific Aim 1 we will collaborate with a user-centered designer to transform treatment guidelines for treating high ketones into intuitive action steps that can readily be followed on a smartphone.
- The shortage of expert diabetes clinicians needed to support patients in the effective use of CKM could limit uptake of this technology. To address this gap, we will evaluate and optimize a digital health model for remote implementation of CKM and smartphone-based DKA prevention guidance that could support the widespread use of this technology by individuals with T1D who do not have acces to specialized diabetes care. In Specific Aim 2 we will conduct clinical trials to evaluate use of this digital model for CKM and patient guidance.
- To have a substantial impact CKM will need to used by T1D patient groups at high risk for DKA. This includes individuals with higher A1c (A1c > 9% associated with 10-14-fold increased DKA risk), individuals from minority communities (DKA hospital admissions in Blacks are 2-fold higher than Whites), and individuals with lower socio-economic status. Each DKA event is an independent risk factor for recurrence (DKA admission risk is 10-fold higher in patients with an episode in the preceding year, with 30-day all-cause DKA readmission rates of 19% in adults with T1D).
In Specific Aim 2 we will be conducting two separate trials at Boston Medical Center (BMC) targeting high risk populations:
1) Post-DKA Hospital Implementation. Patients hospitalized with DKA will be started on CKM with digital treatment guidance (developed in Specific Aim 1). We will compare DKA rates in 52-week period post-hospitalization (while patients are using CKM) with the period pre-hospitalization (no CKM).
2) Outpatient Implementation. This trial will enroll adults with T1D, and will involve 13 weeks with real-time CKM with digital treatment guidance, and 13 weeks blinded CKM (ketone data not visible to the participants). Trial participants will be representative of the lower income and ethnic/minority population who receive care at BMC, which is the largest safety net hospital in New England. We will target enrollment of at least 30% of trial participants with A1c >9%.
- Past experience with continuous glucose monitoring has highlighted the importance of behavioral research to identify potential barriers to the sustained and effective use of technology. In Specific Aim 3 we will conduct extensive mixed methods research – with validated PRO surveys, ecological momentary assessment, and semi-structured interviews – of patient experience with CKM and the digital ketosis management guidance tools in the trial. The learnings from this investigation will drive the development of improved patient training tools to overcome potential barriers to the effective use of CKM, and will provide foundational data for the development of a psychometrically valid and CKM-specific PRO instrument to evaluate patient experience in future clinical trials.
Anticipated Outcome
The digital ketosis management guidance tools to be developed in this project will enable all patients with T1D – including individuals from medically underserved communities who are at high risk for DKA and do not have access to specialized diabetes care – to receive the expert clinical guidance needed for effective use of CKM to prevent DKA.
Evidence from the planned trials that use of CKM reduces high ketones and DKA will provide the foundation for future large-scale multi-center trials to drive changes in the standard-of-care guidelines and insurance coverage for CKM.
The comprehensive mixed methods evaluation of patient experience will identify potential barriers to the sustained and effective use of CKM that need to be addressed to ensure successful adoption of this technology into diabetes care. In addition, the learnings from this investigation will provide foundational data for the development of a psychometrically valid and reliable CKM-specific PRO instrument to evaluate patient experience in future clinical trials.
Relevance to T1D
DKA is an acute, life-threatening complication of diabetes. Despite recent advances in the management of T1D, including continuous glucose monitoring and automated insulin delivery, and the associated substantial reduction in the risk for long term complications and dangerous severe hypoglycemic events, there has not been any improvement in risk for DKA. In fact, over recent decades there has been an alarming surge in DKA rates. US data shows an increase from 2003 to 2017 of DKA incidence from 32 to 61.6 per 10,000 hospital admissions. DKA also adds significantly to overall health care expenditures. US-based studies report hospital charges for DKA admissions ranging from $21,215 to $36,600 per admission. New interventions to reduce the risk for DKA could change this trajectory, improving health outcomes for individuals living with T1D and providing cost savings to the health care system.