Ketone Monitoring in T1D: Effect of SGLT2i During Usual Care and With Insulin Deficiency

Prior treatment

• Unwilling to avoid alcohol during the active study periods, specifically to avoid alcohol for 4 hours prior to any breath ketone measurement
• Use of oral or injected corticosteroids within the past 30 days or planned during the study period
• Pre-menopausal women not using acceptable birth control defined as abstinence, surgical sterilization, hysterectomy, hormonal contraception, IUD or proven effective barrier methods

Other illness

• History of DKA in the past 6 months, or more than 1 episode of DKA in the past 2 years
• Unstable heart disease, including hospitalization for any cardiac or vascular event in the past 6 months.
• Cancer that has been under treatment in the past 6 months, or treatment is likely in the 3 months after signing the consent, not including skin cancer or cancers under long-term hormonal reduction treatment (breast or prostate, no other active treatment)
• Psychiatric condition that interferes with daily activities or diabetes self-care, including substance abuse
• Any illness or condition that may interfere with study measurements, or contraindications for use of SGLT2i, based on investigator discretion (hemoglobinopathy, orthostatic hypotension)
• History of vomiting episodes for any reason in the past 30 days, or hospitalization for cyclic vomiting in the past year
• History of urinary tract infection in the past 3 months

Lab values

• eGFR \<30 ml/min/1.73m2 or hemoglobin \<11.0 g/dL measured in the past year

Other

• Use of insulin degludec, insulin glargine U300 or insulin detemir as basal insulin and unwilling to transition to glargine given in the morning for at least 48 hours before the insulin withdrawal visits
• Use of an SGLT2i in the past 30 days or intolerance to SGLT2i use in the past for any reason
• Currently following or planning to adopt a diet that is low in carbohydrates (defined as \<90 grams of carbohydrate per day) or is expected to be ketogenic
• Taking disulfiram (due to interference with breath ketone measurements)
• Pregnancy, breast-feeding or intention of becoming pregnant during the study time period and up to 30 days after study completion

• Type 1 diabetes for \>1 year
• Age 18 - 75, any gender, race or ethnicity
• HbA1c \<10%
• Stable insulin delivery method for the past 30 days
• Vision of 20/40 or better, including ability to read all device instructions and insulin pump settings
• Use of an insulin pump and ability to make adjustments to pump settings
• Insulin delivery by MDI with basal insulin (glargine U100) given in the morning OR willingness to transition to basal glargine given in the morning for at least 48 hours prior to insulin withdrawal visits
• Use of personal CGM, only Dexcom G6 will be permitted for data consistency
• Use of cellular phone (iOS11 and above or Android) with data capability with connectivity to Dexcom Clarity app and Biosense Ketone Monitoring app
• Willing to share CGM, capillary ketone results and BrACE data with the study group
• Able to understand the study requirements, risks and benefits and able to provide written informed consent
• Able to schedule the visits and perform study related tasks