Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study aims to understand the heart and blood sugar health benefits of using an adjunctive therapy to lower high insulin levels in people with type 1 diabetes. The investigators will also look at people with a specific type of diabetes called Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY) and those without diabetes to help interpret the results. The investigators will use a medication that helps the body get rid of sugar, called and SGLT2 inhibitor, with the goal to reduce the body's insulin requirements. The investigators believe this could lead to better heart and blood sugar health, including a better response to insulin and more available nitric oxide, a gas that helps blood vessels function well. The investigators will compare heart and blood sugar health risk factors in participants with type 1 diabetes, participants with Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), and non-diabetic healthy volunteers under two conditions: high insulin levels typical of type 1 diabetes and normal insulin levels typical of the other two groups.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High insulin | Experimental | Participants will receive a "high insulin infusion" (Hi-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to patients with type 1 diabetes for five hours. |
|
| Normal insulin | Active Comparator | Participants will receive a "normal insulin infusion" (Eu-Ins) prior to quantifying insulin resistance and endothelial function. This infusion will result in participants having insulin levels similar to people without diabetes and people with GCK-MODY for five hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Study Visit 1 | Procedure | Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. The study will randomize participants to first receive a five-hour intravenous insulin infusion to achieve normal plasma insulin concentrations (Eu-Ins) or higher plasma insulin concentrations (Hi-Ins) |
| Measure | Description | Time Frame |
|---|---|---|
| Aim 1: Tissue glucose disposal (TGD) | The primary outcome will be the difference in tissue glucose disposal (TGD) during a hyperinsulinemic, euglycemic clamp between Eu-Ins and Hi-Ins studies. | 8 hours |
| Aim 2: Nitric Oxide (NO) bioavailability | This study aims to determine the difference in hyperinsulinemia-mediated suppression of nitric oxide (NO) bioavailability between Eu-Ins and Hi-Ins studies, as measured by flow mediated dilation (FMD) of the brachial artery. | 8 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary outcome for Aim 1: Differences in endogenous glucose production | This study aims to determine the difference in endogenous glucose production at the end of euinsulinemic vs. hyperinsulinemic infusions | 8 hours |
| Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery |
Not provided
Inclusion Criteria:
Age: 18-60 years BMI: 18-28 kg/m² Weight: ≥ 50 kg
T1DM Participants:
Duration of T1DM: 1-30 years HbA1c: 5.7-7.5% Insulin Therapy: Using automated insulin delivery
GCK-MODY Participants:
HbA1c: 5.7-7.5% Genetic Confirmation: Positive GCK sequencing
Control Participants:
HbA1c: less than 5.5%
** Exclusion Criteria: Severe Hypoglycemia: ≥1 episode in the past 3 months
Comorbidities:
Medications:
Other:
T1DM Participants:
Medications: Any diabetes medication except insulin C-peptide: greater than 0.7 ng/mL (fasting)
GCK-MODY Participants:
None specific
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniel J Moore, MD, PhD | Contact | 615-322-7427 | metabolism@vumc.org |
| Name | Affiliation | Role |
|---|---|---|
| Daniel J Moore, MD, PhD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37232 | United States |
Individual participant data that underlie the results reported in a published article after deidentification (text, tables, figures, and appendices).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug |
|
|
| Study Visit 2 | Procedure | Hyperinsulinemic, euglycemic clamp and flow-mediated dilation (FMD) study. Insulin levels infused during the five-hour insulin infusion will be opposite of the first visit. |
|
| Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor | Drug | Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg). |
|
Through the use of flow mediated dilation (FMD), the study aims to determine nitroglycerin mediated vasodilation of the brachial artery. |
| 8 hours |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
Not provided
Not provided