Vanderbilt Clinical Trials

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 Sex: 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.	Procedure: Study Visit 1 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) Drug: Placebo - T1DM participants in the Hi-Ins study will receive an oral placebo. During the Eu-Ins study they will receive an SGLT2i. - CGK-MODY participants and healthy volunteers will receive placebo in both studies. Procedure: Study Visit 2 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.
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.	Procedure: Study Visit 1 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) Drug: Placebo - T1DM participants in the Hi-Ins study will receive an oral placebo. During the Eu-Ins study they will receive an SGLT2i. - CGK-MODY participants and healthy volunteers will receive placebo in both studies. Procedure: Study Visit 2 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. Drug: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg).

Recruiting Locations

Vanderbilt University medical Center
Nashville, Tennessee 37232

Contact:
Justin M Gregory, MD, MSCI
615-322-7427
metabolism@vumc.org

More Details

Status: Recruiting
Sponsor: Vanderbilt University Medical Center

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.