Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes

Summary

The investigators will test the hypothesis that, in adults with type 1 diabetes (T1D), glucagon-like peptide-1 receptor agonism (GLP-1RA, i.e. dulaglutide) enhances insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.

Eligibility

Inclusion 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 - English or Spanish speaking

Exclusion criteria:

* 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
* 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

Conditions3

Interventions1

Locations1 site

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• A Study of Dulaglutide (LY2189265) 3.0 mg and 4.5 mg in Pediatric Participants With Type 2 Diabetes Mellitus (AWARD-PEDS PLUS) — Eli Lilly and Company

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