Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Aim 1: Tissue glucose disposal (TGD)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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%
排除标准
- •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
- •Any thiazide diuretic
- •Any oral contraceptive pill with greater than 35 mcg ethinyl estradiol
- •Growth hormone
- •Any immunosuppressant
- •Antihypertensive
- •Any antihyperlipidemic
- •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
研究组 & 干预措施
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.
干预措施: Study Visit 1 (Procedure)
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.
干预措施: Placebo (Drug)
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.
干预措施: Study Visit 2 (Procedure)
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.
干预措施: Study Visit 1 (Procedure)
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.
干预措施: Placebo (Drug)
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.
干预措施: Study Visit 2 (Procedure)
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.
干预措施: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitor (Drug)
结局指标
主要结局
Aim 1: Tissue glucose disposal (TGD)
时间窗: 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
时间窗: 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.
次要结局
- 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)
研究者
Daniel Moore
Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes
Vanderbilt University Medical Center