Glucokinase-Maturity Onset Diabetes of the Young (GCK-MODY), Healthy Volunteer, MODY2 Diabetes, Type 1 Diabetes Mellitus
Conditions
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)
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.
Interventions
PROCEDUREStudy 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)
DRUGPlacebo
* 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.
PROCEDUREStudy 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.
Concurrent with starting the five-hour infusion, T1DM participants in the Eu-Ins study will receive an SGLT2i dose (empagliflozin 25 mg).
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactDaniel J Moore, MD, PhD
Outcome results
None listed