- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04118374
A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: T. Jordan Smith, RN, BSN
- Phone Number: 615-936-6324
- Email: metabolism@vumc.org
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University Medical Center
-
Contact:
- T. Jordan Smith, RN, BSN
- Phone Number: 615-936-6324
- Email: metabolism@vumc.org
-
Principal Investigator:
- Justin M Gregory, MD, MSCI
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Standard Carb Diet then Low Carb Diet
|
Approximately 50% of caloric intake will come from carbohydrate consumption.
Approximately 25% of caloric intake will come from carbohydrate consumption.
|
Experimental: Low Carb Diet then Standard Carb Diet
|
Approximately 50% of caloric intake will come from carbohydrate consumption.
Approximately 25% of caloric intake will come from carbohydrate consumption.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in insulin sensitivity - diet 1
Time Frame: baseline to 1 week
|
Change in insulin sensitivity based on diet
|
baseline to 1 week
|
Change in insulin sensitivity - diet 2
Time Frame: baseline to 1 week
|
Change in insulin sensitivity based on diet
|
baseline to 1 week
|
Change in endothelial function - diet 1
Time Frame: baseline to 1 week
|
will quantify brachial artery, endothelium-dependent flow-mediated vasodilation using high-resolution ultrasound
|
baseline to 1 week
|
Change in endothelial function - diet 2
Time Frame: baseline to 1 week
|
will quantify brachial artery, endothelium-dependent flow-mediated vasodilation using high-resolution ultrasound
|
baseline to 1 week
|
Collaborators and Investigators
Investigators
- Principal Investigator: Justin M Gregory, MD, MSCI, Vanderbilt University Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 190630
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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