Atherosclerosis, Cardiovascular Diseases, Insulin Resistance, Type 2 Diabetes
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
Stanford University
Merck Sharp & Dohme LLC
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 in Adipose Tissue Depots to Measure Metabolic Flexibility | Time to collect tissue collected during surgery (up to 15 minutes) | The rate of lipolysis was measured under basal, isoproterenol-stimulated, and insulin-suppressed conditions in adipose tissue depots (epicardial, pericardial, and subcutaneous) treated with and without Ertugliflozin. Lipolysis was quantified using a colorimetric assay to determine metabolic flexibility. Cardiac adipose tissue explants cultured with ertugliflozin compared to mock condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine Secretion Profiles in Adipose Tissue Depots | Time to collect tissue collected during surgery (up to 15 minutes) | Levels of cytokines, including MCP1, TNF-β, IL-6, IFN-γ, and IL1-β, were measured in the culture medium of treated and untreated adipose tissue depots (epicardial, pericardial, and subcutaneous) using Luminex assays. Cytokine levels were used to characterize inflammation and response to Ertugliflozin treatment in cardiac adipose tissue explants) and isolated adipocytes after culture with Ertugliflozin vs mock condition. |
| Adipose Cell Size Distribution in Pericardial and Subcutaneous Tissue | Time to process tissue samples collected during surgery (up to 15 minutes). | Adipose cell size distribution was assessed in subcutaneous and pericardial adipose tissue samples using osmium fixation and cell diameter measurements. The relationship between cell size and Ertugliflozin treatment was analyzed. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTracey McLaughlin, MD
Stanford University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.93 years STANDARD_DEVIATION 16.76 |
| BMI | 33.4 kg/m² STANDARD_DEVIATION 7.38 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 61 |
| other Total, other adverse events | 0 / 61 |
| serious Total, serious adverse events | 0 / 61 |
Outcome results
None listed