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

  • End date
    Feb 28, 2024
  • participants needed
  • sponsor
    Vanderbilt University Medical Center
Updated on 27 September 2021


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.

Condition type 1 diabetes mellitus, diabetes type 1, type i diabetes mellitus, type 1 diabetes, insulin-dependent diabetes, Insulin dependent diabetes mellitus, diabetes mellitus type 1, iddm, Diabetes Mellitus, Type 1
Treatment Low carb diet, Standard Carb Diet
Clinical Study IdentifierNCT04118374
SponsorVanderbilt University Medical Center
Last Modified on27 September 2021


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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 18-33 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%
any antioxidant vitamin supplement (<2 weeks before STUDY visit)
any systemic glucocorticoid
any antipsychotic
atenolol, metoprolol, propranolol
any thiazide diuretic
any OCP with > 35 mcg ethinyl estradiol
growth hormone
any immunosuppressant
any antihypertensive
any antihyperlipidemic
Tanner stage < 5
peri or postmenopausal woman
active smoker
gluten-free diet requirement
Additional exclusion criteria for T1DM subjects
any diabetes medication except insulin
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