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

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

Sponsors

Lead sponsor: Vanderbilt University Medical Center

Source Vanderbilt University Medical Center
Brief 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).

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.

Overall Status Not yet recruiting
Start Date October 1, 2019
Completion Date May 1, 2020
Primary Completion Date May 1, 2020
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in insulin sensitivity - diet 1 baseline to 1 week
Change in insulin sensitivity - diet 2 baseline to 1 week
Change in endothelial function - diet 1 baseline to 1 week
Change in endothelial function - diet 2 baseline to 1 week
Enrollment 10
Condition
Intervention

Intervention type: Other

Intervention name: Standard Carb Diet

Description: Approximately 50% of caloric intake will come from carbohydrate consumption.

Intervention type: Other

Intervention name: Low Carb Diet

Description: Approximately 25% of caloric intake will come from carbohydrate consumption.

Eligibility

Criteria:

Inclusion Criteria:

- Age: 18-60

- HbA1c: 5.9-9.0%

- Insulin delivery: must be on an insulin pump

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

- BMI 18-28 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

Gender: All

Minimum age: 18 Years

Maximum age: 60 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Justin M Gregory, MD, MSCI Principal Investigator Vanderbilt University Medical Center
Overall Contact

Last name: Tyler J Smith, BSN

Phone: 6159366324

Email: [email protected]

Location
facility contact investigator Vanderbilt University Tyler J Smith, BSN 615-478-5987 [email protected] Justin M Gregory, MD, MSCI Principal Investigator
Location Countries

United States

Verification Date

October 2019

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Vanderbilt University Medical Center

Investigator full name: Justin Gregory

Investigator title: Assistant Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Standard Carb Diet then Low Carb Diet

Arm group type: Experimental

Arm group label: Low Carb Diet then Standard Carb Diet

Arm group type: Experimental

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov