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

Vanderbilt University Medical Center14 enrolled

Overview

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).

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 1

Interventions

Standard Carb DietOTHER

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

Low Carb DietOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (1)

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Change in Insulin Sensitivity Assessed as Glucose Infusion Rates

Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp.To express GIR in mg of glucose per kg of fat-free mass per minute (mg/kg FFM/min), we divided the dextrose infusion rate by the fat-free mass determined by DEXA. Insulin sensitivity showed no significant difference between diets. GIR was 8.1 mg/kg FFM/min after the RCD and 8.6 mg/kg FFM/min after the SCD.

Time frame: week 1 and week 5

Data from ClinicalTrials.gov

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