Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

Eligibility Criteria

• * History of type 1 diabetes, duration \> 5 years
• * Age 18-40 years
• * HbA1c \< 8.5%
• * BMI 19-34.9 kg/m2
• * Using insulin for diabetes treatment only (multiple daily injections or insulin pump with or without sensor augmentation)
• * On stable regimen of non-diabetic medications for the last 6 months
• * All screening labs within normal limits or not clinically significant
• * C-peptide \<0.6 ng/ml
• * Pregnancy or currently breastfeeding
• * Smoking history within 6 months
• * History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) as well as clinically significant cardiac arrhythmias or conduction disorders
• * Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers).
• * Known hypersensitivity to perflutren (contained in Definity© contrast)
• * Screening O2 saturation \<90%
• * Musculoskeletal condition preventing participation in exercise testing or exercise training
• * Acute or unstable disease other than T1D
• * Hypoglycemia unawareness (based on Clarke's questionnaire)
• * History of gastroparesis, severe gastroesophageal reflux, pancreatitis, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
• * Anemia (hemoglobin \<12 g/dL in women, hemoglobin \<13 g/dL in men), eosinophilia (absolute eosinophil count \>500 cells/microliter) leukopenia (total white blood cells \<4,000 cells/microliter)
• * Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days
• * Hospital admission for DKA within 1 year