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

2019-10-15 11:11:34 | BioPortfolio


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 Design


Diabetes Mellitus, Type 1


Standard Carb Diet, Low Carb Diet


Vanderbilt University
United States


Not yet recruiting


Vanderbilt University Medical Center

Results (where available)

View Results


Published on BioPortfolio: 2019-10-15T11:11:34-0400

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Medical and Biotech [MESH] Definitions

A diet prescribed in the treatment of diabetes mellitus, usually limited in the amount of sugar or readily available carbohydrate. (Dorland, 27th ed)

A diet that contains limited amounts of CARBOHYDRATES. This is in distinction to a regular DIET.

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

Regular course of eating and drinking adopted by a person or animal. This does not include DIET THERAPY, a specific diet prescribed in the treatment of a disease.

A diet that contains limited amounts of fat with less than 30% of calories from all fats and less than 10% from saturated fat. Such a diet is used in control of HYPERLIPIDEMIAS. (From Bondy et al, Metabolic Control and Disease, 8th ed, pp468-70; Dorland, 27th ed)

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