Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes

Early Phase 1

Not yet recruiting

• Conditions: Type 1 Diabetes Mellitus; Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY); MODY2 Diabetes; Healthy Volunteer
• Interventions: Procedure: Study Visit 1; Drug: Placebo; Procedure: Study Visit 2; Drug: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

• Registration Number: NCT06609356
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-20
• Study First Submitted QC: 2024-09-20
• Study First Posted: 2024-09-24
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-17
• Study Start: 2025-06-01
• Primary Completion: 2027-07
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 27

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%

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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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High insulin	Study Visit 1	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.
High insulin	Placebo	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.
High insulin	Study Visit 2	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	Study Visit 1	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.
Normal insulin	Placebo	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.
Normal insulin	Study Visit 2	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.
Normal insulin	Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor	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.

Primary Outcome Measures

Name	Time	Method
Aim 1: Tissue glucose disposal (TGD)	8 hours	The primary outcome will be the difference in tissue glucose disposal (TGD) during a hyperinsulinemic, euglycemic clamp between Eu-Ins and Hi-Ins studies.
Aim 2: Nitric Oxide (NO) bioavailability	8 hours	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.

Secondary Outcome Measures

Name	Time	Method
Secondary outcome for Aim 1: Differences in endogenous glucose production	8 hours	This study aims to determine the difference in endogenous glucose production at the end of euinsulinemic vs. hyperinsulinemic infusions
Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery	8 hours	Through the use of flow mediated dilation (FMD), the study aims to determine nitroglycerin mediated vasodilation of the brachial artery.

Trial Locations

Locations (1)

Vanderbilt University medical Center; 🇺🇸 Nashville, Tennessee, United States