Insulin Sensitivity, Type2 Diabetes
Conditions
Brief summary
The aim is to test in T2DM patients, whether, compared to placebo, 12 weeks of SGLT-2 inhibitor improves post-absorptive, post-insulin infusion or postprandial insulin action to enhance Cardiac Muscle vascular function and whether changes correlate with improved GV or postprandial hyperglycemia
Detailed description
The investigators will study 32 T2DM subjects measuring cardiac muscle vascular function before and after a 4 hour insulin clamp ( protocol A) and before and after a mixed meal (protocol B). Then subjects will be randomized into 2 groups: Group 1 will undergo a 12 week intervention of Empagliflozin, and Group 2 will do 12 weeks of Placebo. The intervention will be single blinded. At the end of the 12 week intervention subjects will repeat protocol A and B. The study's primary objective is to assess whether, compared to placebo, 12 weeks of Empagliflozin improves post-absorptive or postprandial insulin action to enhance myocardial perfusion (MP) and whether changes of MP correlate with improved glucose variability or postprandial hyperglycemia
Interventions
DRUGEmpagliflozin 25 MG
SGLT-2 inhibitor
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* A1C \> 6.5 and \<9% * Never on SGLT-2i (eg: Jardiance, Invokana, Farxiga, Steglatro) * On stable dose of oral hypoglycemic agents \>3 months * On stable dose of other medications for \>3 months * BMI-\<35
Exclusion criteria
* • Smoking presently or in the past 6 months * Taking insulin * BP \>160/90 * BMI \>35 * History of congestive heart failure, ischemic heart disease, severe pulmonary disease, liver or kidney disease. * Any vascular disease such as myocardial infarction, stroke, peripheral vascular disease * History of cancer or psychiatric disease * Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI). * Pregnant or breastfeeding. * Known hypersensitivity to perflutren (contained in Definity) * Screening O2 saturation \<90% * History of recurrent UTI/bladder/kidney infections-eGFR is below 45 mL/min/1.73.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial microvascular perfusion | Between baseline and 12 weeks treatment | Vascular measure of myocardial perfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Dilation (FMD) Vascular measure of conduit artery stiffness Change in Flow Mediated Dilation (FMD) between baseline and after 2 hour insulin clamp Vascular measure of conduit artery stiffness Flow Mediated Dilation ( FMD) | Between baseline and 12 weeks of treatment. | Vascular measure of conduit artery stiffness |
| Augmentation Index ( AI) | Between baseline and 12 weeks of treatment. | Measurement of central artery stiffness |
| Pulse Wave Velocity ( PWV) | Between baseline and 12 weeks of treatment | Measurement of central artery stiffness |
Countries
United States
Contacts
Primary ContactEugene J Barrett, MD PhD
Backup ContactLee Hartline, MEd
Outcome results
None listed