Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes
Purpose
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.
Conditions
- Type 1 Diabetes Mellitus
- Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY)
- MODY2 Diabetes
- Healthy Volunteer
Eligibility
- Eligible Ages
- Between 18 Years and 60 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
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: - Any hospital admissions for diabetic ketoacidosis in the past 6 months - SBP greater than 140 mmHg and DBP greater than 100 mmHg - eGFR by MDRD equation of less than 60 mL/min/1.73 m² - AST or ALT greater than 2.5 times ULN - Hct less than 35% Medications: - Any antioxidant vitamin supplement within 2 weeks before the study - Any systemic glucocorticoid - Antipsychotics - Atenolol, Metoprolol, Propranolol - Niacin - Any thiazide diuretic - Any oral contraceptive pill with greater than 35 mcg ethinyl estradiol - Growth hormone - Any immunosuppressant - Antihypertensive - Any antihyperlipidemic Other: - Pregnancy - Tanner stage less than 5 - Peri- or post-menopausal women - Active smoker T1DM Participants: Medications: Any diabetes medication except insulin C-peptide: greater than 0.7 ng/mL (fasting) GCK-MODY Participants: None specific
Study Design
- Phase
- Early Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental High insulin |
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. |
|
Active Comparator Normal insulin |
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. |
|
Recruiting Locations
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Vanderbilt University Medical Center