A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04118374
• Other study ID #: 190630
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2019
• Est. completion date: August 30, 2024

Study information

• Verified date: May 2024
• Source: Vanderbilt University Medical Center
• Contact: T. Jordan Smith, RN, BSN
• Phone: 615-936-6324
• Email: metabolism[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will test the hypothesis that reducing insulin doses using a low carbohydrate diet (LCD) will be associated with with improved insulin sensitivity (Aim 1) and blood vessel health (Aim 2).

Description:

Insulin resistance (IR) is consistently found in patients with type 1 diabetes (T1DM) and pathophysiologically links T1DM with atherosclerotic disease. IR and nascent atherosclerosis, as characterized by endothelial dysfunction, are present early in T1DM. Although atherosclerosis leads to cardiovascular disease (CVD)-the predominant cause of death in T1DM-the early cardiometabolic processes driving atherosclerosis are not currently well-characterized. My overarching hypothesis is that IR and endothelial dysfunction in T1DM are, in part, iatrogenic, occurring as a function of nonphysiologic insulin delivery.

Previous research shows IR in T1DM is closely related to iatrogenic hyperinsulinemia. Iatrogenic hyperinsulinemia in T1DM results from injecting insulin into subcutaneous tissue rather than delivering insulin more physiologically into the hepatic portal vein. Hyperinsulinemia, per se, is closely linked with IR and independently predicts CVD in diabetic and nondiabetic populations. Thus, peripheral insulin delivery brings about unintended adverse cardiometabolic consequences in T1DM. The investigators propose a practical intervention to diminish iatrogenic hyperinsulinemia and thereby mitigate CVD risk. The investigators hypothesize that a reduction in iatrogenic hyperinsulinemia brought about by a low carbohydrate diet (LCD) will independently correlate with improved insulin sensitivity (Aim 1) and endothelial function (Aim 2).

In this pilot study, the investigators will mechanistically dissect the contribution of iatrogenic hyperinsulinemia to IR and endothelial dysfunction in 8 adults with T1DM using a crossover study of LCD vs. standard carbohydrate diet (SCD) to experimentally modify hyperinsulinemia. The investigators will quantify insulin sensitivity using hyperinsulinemic, euglycemic clamps and measure endothelium-dependent flow mediated vasodilation using high-resolution ultrasound.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age: 18-60

• HbA1c: 5.6-9.0%

• Insulin delivery: must be on an insulin pump

• Glucose Monitor: must use a continuous glucose monitor (CGM)

• BMI 18-33 kg/m^2

• Body Mass >/= 50 kg ( 110 lbs)

Exclusion Criteria:

• severe hypoglycemia : >/= 1 episode in the past 3 months

• diabetes comorbidities (>= 1 trip to emergency department for poor glucose control in the past 6 months,

• New York Heart Association Class II-IV cardiac functional status

• SBP > 140 and DBP > 100 mmHg,

• eGFR by MDRD equation of <60 mL/min/1.73m^2

• AST or ALT > 2.5 times the upper limit of normal

• HCT <35%

medications

• any antioxidant vitamin supplement (<2 weeks before STUDY visit)

• any systemic glucocorticoid

• any antipsychotic

• atenolol, metoprolol, propranolol

• niacin

• any thiazide diuretic

• any OCP with > 35 mcg ethinyl estradiol,

• growth hormone

• any immunosuppressant

• any antihypertensive

• any antihyperlipidemic

other:

• pregnancy

• Tanner stage < 5

• peri or postmenopausal woman

• active smoker

• gluten-free diet requirement

Additional exclusion criteria for T1DM subjects

• any diabetes medication except insulin

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hyperinsulinism
• Insulin Resistance

Intervention

Other:
• Standard Carb Diet
Approximately 50% of caloric intake will come from carbohydrate consumption.
• Low Carb Diet
Approximately 25% of caloric intake will come from carbohydrate consumption.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in insulin sensitivity - diet 1	Change in insulin sensitivity based on diet	baseline to 1 week
Primary	Change in insulin sensitivity - diet 2	Change in insulin sensitivity based on diet	baseline to 1 week
Primary	Change in endothelial function - diet 1	will quantify brachial artery, endothelium-dependent flow-mediated vasodilation using high-resolution ultrasound	baseline to 1 week
Primary	Change in endothelial function - diet 2	will quantify brachial artery, endothelium-dependent flow-mediated vasodilation using high-resolution ultrasound	baseline to 1 week