The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans

Study Overview
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Brief Summary
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Arterial vascular disease is the major cause of morbidity and mortality for Type 1 diabetic patients (DM1). Metabolic insulin resistance (metIR), even in the absence of hyperglycemia, conveys a 1.5 to 3-fold increased CVD risk in the general population. Metabolic Insulin Resistance (MetIR) has been repeatedly shown to be prevalent in adults and adolescents with DM1. MetIR in obesity and DM2 are accompanied by vascular insulin resistance (vasIR) which is characterized by impaired vasodilatory action of insulin on resistance or microvascular vessels. VasIR has not been systematically studied in DM1. We hypothesize that in young adults DM1 impairs both baseline and insulin-responsive vascular function throughout the arterial vasculature.

Detailed Description
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In our study, 20 healthy control subjects will be compared to 20 DM1 patients (18-40 yrs). We will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a euglycemic insulin clamp.

Official Title
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The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans

Conditions
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Diabetes Type 1

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 BMI ≤ 25 Healthy with no chronic illness (control group only) Normal screening labs or no clinically significant values DM1 subjects will have been on insulin for at least 5 years and HbA1c <9 Exclusion Criteria: First degree relative with Type 1 or 2 Diabetes (for control group only) Smoking presently or in the past 6 months Medications that affect the vasculature (except ACE or ARB in DM1 subjects, although they will need to be off these drugs for 2 weeks prior to study). Elevated LDL cholesterol > 160 BP <100/60 or >160/90 Pulse oximetry <90% Pregnant or breastfeeding History of cardiovascular disease, cerebral vascular disease, peripheral vascular disease, liver disease Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam ). Known hypersensitivity to perflutren (contained in Definity) For DM1 group: HbA1c ≥ 9 Microalbuminuria Retinipathy Ketoacidosis within the past year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 1 Diabetic<br>Type 1 Diabetic | |
| Control<br>normal healthy control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Augmentation Index | vascular measure | baseline | 
| Pulse Wave Velocity | vascular measure | baseline | 
| Flow Mediated Dilation | vascular measure | Baseline | 
| Contrast Enhanced Ultrasound | vascular measure | baseline | 
| Augmentation Index | vascular measure | after 2 hour insulin clamp | 
| Pulse Wave Velocity | vascular measure | after 2 hour insulin clamp | 
| Flow Mediated Dilation | vascular measure | after 2 hour insulin clamp | 
| Contrast Enhanced Ultrasound | vascular measure | after 2 hour insulin clamp | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Type 1, Vascular Function