Artificial Pancreas Technology to Reduce Glycemic Variability and Improve Cardiovascular Health in Type 1 Diabetes

This study will examine the potential cardiovascular effect(s) of artificial pancreas (AP) technology in patients with type 1 diabetes. AP technology is a system of devices that closely mimics the glucose-regulating function of a healthy human pancreas. It includes an insulin pump and a continuous glucose monitor (CGM). In this study, the investigators will research whether improvements in blood glucose levels and blood glucose variability will in turn decrease biomarkers of inflammation and endothelial dysfunction while improving cardiovascular function.

Inclusion Criteria:Clinical diagnosis, based on World Health Organization criteria, of type 1 diabetes for at least one yearCurrently using insulin for at least six monthsAges 18-≤40 yearsHemoglobin A1c <10.5%Body mass index 18-30 kg/m2Blood pressure <140/90 mmHgFor females, not currently known to be pregnant or breastfeedingIf female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of childbearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinuedBoth pump and MDI users will use insulin parameters such as carbohydrate ratio and correction factors consistently in order to dose insulin for meals or corrections; pump users will have history of entering this information into their pumpWillingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in useAccess to internet and willingness to upload data during the study as needed, including data generated prior to the start of the studyCurrent use of a glucometer that is downloadable; or willingness to use a study glucometerInvestigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocolWillingness to use personal lispro (Humalog) or aspart (Novolog) and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the studyTotal daily insulin dose (TDD) at least 10 U/day.Willingness not to start any new non-insulin glucose-lowering agent during the trialExclusion Criteria:Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollmentDiagnosis of diabetic ketoacidosis in the 12 months prior to enrollmentPrior diagnosis of cardiac disease (e.g. myocardial infarction, congestive heart failure)Cerebrovascular accident in the 12 months prior to enrollmentConditions that would make use of a CGM difficult (e.g., blindness, severe arthritis, immobility)Current use of oral/inhaled glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the studyConcurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas)Hemophilia or any other bleeding disorderCurrently being treated for a seizure disorderA medical condition or medication, which in the opinion of the investigator or designee, would put the participant or study at riskCurrent use of an automated insulin delivery system (besides LGS and PLGS) such as Medtronic 670G, Control-IQ or DIY system (or unwillingness to discontinue automated insulin delivery for three months before enrollment and the duration of the trial)Current smokers or those who have quit smoking <2 years agoScreening Electrocardiogram (ECG) findings indicative of arrhythmia, sinus node disease, or ischemic heart diseaseDiagnosis of peripheral neuropathy (assessed by monofilament examination), macroalbuminuria (urine albumin:creatinine >300 mg per g), or retinopathy beyond mild, nonproliferative retinopathyUnstable (i.e., dose adjustment less than 4 weeks prior to study enrollment) doses of vasoactive medications (e.g., calcium channel blockers, statins, nitrates, alpha-blockers, beta-blockers, ACE inhibitors, etc.)Uncontrolled resting arterial hypertensionHistory of hypersensitivity or prior adverse reaction to Definity Microbubble InfusionHistory of hypersensitivity or prior adverse reaction to regadenoson InfusionCurrent enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial