Objective
The objectives of the study are basically to gain an understanding of the relationship between exhaled breath acetone and blood beta hydroxybutyrate as measured by a hand held meter during usual care, during insulin deficiency on day of testing in the research unit; then with the testing repeated while the patient takes an SGLT2i tablet, first for 2 weeks at home, then during insulin deficiency. The overarching objective is to determine whether measurements of breath ketones can provide information that is valuable to persons with T1D, either for day to day activities (exercise, missed meals), or for warning about impending DKA. Secondarily, we want to know whether persons with T1D find the breath analyzer device easy and convenient to use.
Background Rationale
The background for this study emerged with urgency as the new class of drugs called SGLT2 inhibitors were found to offer protection from progression of kidney and heart disease in persons with T2D. Because they cause the body to make more ketones, and rates of DKA went up when people with T1D took the drugs, they are not advised for persons with T1D currently. In order to reap the benefits of the drugs, they should be studied in T1D, but that requires improved strategies to identify and provide early management of high ketones. The current strategies of either fingerstick testing or urine testing are cumbersome for routine monitoring, so people only use them when they have symptoms, which is often too late. We propose to test a breath ketone analyzer that can be used routinely for monitoring of ketones. Whether it will provide the early warning of elevated ketones is unknown, but worth testing. It is certainly more convenient and/or cheaper than the other measurements.
Description of Project
Type 1 diabetes is a chronic illness that require life long insulin administration to avoid the devastating acute metabolic decompensation known as diabetic ketoacidosis or DKA. DKA is life-threatening and can result from simple omission of one or two injections of insulin or insulin pump malfunction. Currently, about 4% of persons with T1D develop DKA each year that require hospitalization, often in ICU. Avoidance of DKA is problematic because the symptoms are non-specific and occur too late, so ketone testing, if done, is often too little too late. Early detection of elevated ketones requires specific testing either in blood or urine. Currently there is not a good way to track ketone production with any frequency. The blood testing with a ketone meter requires a fingerstick, and is expensive. Urine testing may not identify lower levels of ketones and is highly inconvenient. Novel ways to test ketones are in development. One such method is through a breath ketone analyzer. The breath ketone analyzer measures acetone, which is a different ketone than is typically measured either at home or in the hospital in persons with T1D. Breath ketone analyzers are used by persons adopting a ketogenic diet, and levels of breath acetone reflect ketogenesis when used for this purpose. Whether breath acetone correlates, that is rises and falls in a similar manner, as the blood ketone called beta hydroxybutyrate is unknown. Whether measuring breath acetone will be useful for early identification of ketone generation in persons with T1D is entirely unknown. This study proposes to compare a breath ketone analyzer with the accepted blood beta hydroxybutyrate measurement when people with T1D are at home, and on one day in the research unit after withholding insulin. In the second part of the study, persons with T1D will take a pill in the class of SGLT2 inhibitors, which have been shown to offer protection from progression of kidney disease and heart failure. These drugs cause an increase in blood ketones, which is unnoticed in persons with type 2 diabetes, but can lead to DKA in persons with T1D. Only a few people with T1D developed DKA in studies where they took an SGLT2i, but the number was double compared to those taking a placebo. Volunteers for the study will take an SGLT2i pill daily and monitor their ketones closely with the breath ketone analyzer and the fingerstick testing device for 2 weeks, followed by a day on the research unit where insulin will be temporarily withheld and ketones monitored closely until they reach a threshold that can easily be reversed and does not cause symptoms.
Anticipated Outcome
The anticipated outcome is that testing breath acetone in persons with T1D will correlate modestly with blood beta hydroxybutyrate testing during day to day activities and during insulin deficiency. We also expect to see higher ketone levels as measured by both types of devices in persons taking SGLT2i drugs for 2 weeks, and when taking the drug plus experiencing insulin deficiency. We hope to find out whether measuring breath acetone provides and early warning for rising ketones that could be hazardous to persons with T1D.
Relevance to T1D
This study his highly relevant to persons with T1D for several reasons. If testing breath ketones is shown to provide early warning for impending DKA in time to allow persons with T1D to mitigate the risk by simple measures such as drinking extra fluid, adding carbohydrates and insulin at home, then hospitalizations for DKA will be reduced. If persons with T1D develop an understanding of their "ketone status" by frequent measurements of breath acetone that allows them to keep ketones to a minimum by modifying behaviors at home, then the risks of DKA while taking SGLT2i will be reduced. Persons with T1D may be able to realize the benefits of these important drugs without incurring risks of life-threatening illness.