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

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
• Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY)
• MODY2 Diabetes
• Healthy Volunteer

Interventions

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).

Sponsors & Collaborators

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Daniel J Moore, MD, PhD · Vanderbilt University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-07-03

Primary Completion

2027-07-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations