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

NCT06609356 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 240996
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes Mellitus; MODY2 Diabetes; Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY); Healthy Volunteer

Keywords

type 1 diabetes mellitus; with Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY); nitric oxide; sodium-glucose cotransporter-2 inhibitors (SGLT2i); healthy volunteer; insulin sensitivity; flow-mediated vasodilation (FMD)

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (2)

• Secondary outcome for Aim 1: Differences in endogenous glucose production

  8 hours

• Secondary outcome for Aim 2: Nitroglycerin mediated vasodilation of the brachial artery

  8 hours

Study Arms (2)

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.

Procedure: Study Visit 1; Drug: Placebo; Procedure: Study Visit 2

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.

Procedure: Study Visit 1; Drug: Placebo; Procedure: Study Visit 2; Drug: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor

Interventions

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)

High insulin; Normal insulin

Placebo DRUG

* 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.

High insulin; Normal insulin

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.

High insulin; Normal insulin

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).

Normal insulin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• Daniel J Moore, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel J Moore, MD, PhD

CONTACT

615-322-7427; metabolism@vumc.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 24, 2024
• Study Start: July 3, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

US (1)