Cardiovascular Diseases, Atherosclerosis, Type 2 Diabetes, Insulin Resistance
Conditions
Keywords
Epicardial Adipose Tissue, SGLT2 Inhibitor
Brief summary
The purpose of this study is to learn if Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) medications enhance beneficial properties of epicardial adipose tissue including metabolic flexibility, insulin sensitivity, decreased cell size and reduced inflammation.
Interventions
DRUGErtugliflozin
Adipose tissue samples collected from participants were treated with Ertugliflozin at a concentration of 25 µM in vitro. This treatment was applied in a laboratory setting to assess the effects of Ertugliflozin on lipolysis, inflammatory cytokine release, and gene expression in epicardial, pericardial, and subcutaneous adipose tissue
Sponsors
Merck Sharp & Dohme LLC
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
in vitro experimental study with treated and control tissue samples
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* patient at Stanford Cardiovascular Surgery clinic who is scheduled for cardiac bypass surgery or vascular surgery * history of Diabetes Mellitus Type 2 currently diet controlled, or on metformin or dpp4 inhibitors
Exclusion criteria
* allergy or intolerance to interventional medication * currently taking insulin, glp-1 inhibitors, or sulfonylureas
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of isoproterenol-stimulated lipolysis to measure metabolic flexibility in epicardial adipose tissue samples. | Time to collect tissue collected during surgery (up to 15 minutes) | Analysis will be performed using Lipolysis Colorimetric Assay and measured by glycerol content on standard curve. Indirect effects of SGLT2i in vivo in epicardial adipose tissue will be compared to Glipizide by measuring rate of lipolysis, or breakdown of adipose in to free fatty acids. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average insulin mediated glucose uptake (IMGU) to measure insulin sensitivity in epicardial adipose tissue samples. | Time to collect tissue collected during surgery (up to 15 minutes) | Mature adipocytes will be isolated, cultured, and treated with 2-NBDG, a fluorescently-labeled deoxyglucose analog, as a probe for the detection of glucose uptake measured by excitation/emission of florescence in the mature cells. |
| Characterization of the inflammatory cytokine expression profile in epicardial adipose tissue samples. | Time to collect tissue collected during surgery (up to 15 minutes) | Analysis will be performed using Luminex to measure levels of inflammatory cytokines on the human adipocyte panel. |
| Distribution of adipose cell size in epicardial tissue. | Time to collect tissue collected during surgery (up to 15 minutes) | After tissue collection and osmium fixation, adipose cell size will be determined by Beckman Coulter Multisizer III, and described via a mathematical model to estimate peak diameter, fat storage capacity, size variability, and % small cells. |
Countries
United States
Outcome results
None listed