Effects of Walking and Heating on Vascular Function in Diabetic Patients

Study Overview
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Brief Summary
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The purpose of the present study is to determine the effects of increased walking and lower body heating on leg vascular function in patients with type 2 diabetes (T2D).

Detailed Description
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The notion that habitual aerobic exercise increases insulin-induced vasodilation is largely founded on rodent studies, hence the urgent need for human studies, especially in patients with type 2 diabetes (T2D). For example, it remains unknown if increased walking, the most common form of physical activity, enhances skeletal muscle vasodilator actions of insulin in T2D. In addition, the molecular mechanisms by which exercise improves vasoreactivity to insulin have not been examined in humans. The investigators propose that in T2D patients who are sedentary (i.e., the vast majority), increased leg blood flow with walking or local heating signifies a vital strategy to correct vascular insulin resistance. This study will establish whether increased physical activity and associated hemodynamic forces (e.g., shear stress) are a direct form of vascular medicine in humans.

Official Title
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Restoring Vasodilator Actions of Insulin in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus, Obesity

Intervention / Treatment
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* Behavioral: Walking
* Behavioral: Lower body heating


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes who are overweight and obese (BMI 25-50 kg/m2), 35 to 65 years of age, and sedentary (<60 minutes structured exercise/week). Healthy volunteers without type 2 diabetes: 35 to 65 years of age. Exclusion Criteria: Cardiovascular disease including myocardial infraction, heart failure, coronary artery disease, stroke; renal or hepatic diseases; active cancer; autoimmune diseases; immunosuppressant therapy; excessive alcohol consumption (>14 drinks/week for men; >7 drinks/week for women); current tobacco use; pregnancy; mobility limitations; foot ulcers; diabetic neuropathy uncontrolled hypertension (>=180 systolic / 100 diastolic mmHg)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to either a walking, a lower body heating, or no intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Walking intervention<br>The walking program will consist of 45 minutes of walking (at a moderate pace) 5 days per week for 8 weeks. | Behavioral: Walking<br>* The walking program will consist of 45 minutes of walking (at a moderate pace) 5 days per week for 8 weeks.<br>|
| No Intervention: Control<br>Subjects will be instructed to continue their usual lifestyle for 8 weeks. | |
| Experimental: Lower body heating<br>This intervention consists of 60 minutes of lower body heating (40-42 degree C) 7 days per week for 7 days. | Behavioral: Lower body heating<br>* This intervention consists of 60 minutes of lower body heating (40-42 degree C) 7 days per week for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | Measure of flow-mediated dilation | Change from baseline flow-mediated dilation at 7 days (heating intervention) or 8 weeks (exercise intervention) | 
| Leg blood flow | Measure of blood flow | Change from baseline insulin-stimulated leg blood flow at 7 days (heating intervention) or 8 weeks (exercise intervention) | 
| Blood glucose | Measure of blood glucose | Change from baseline blood glucose at 7 days (heating intervention) or 8 weeks (exercise intervention) | 
| Plasma insulin | Measure of plasma insulin | Change from baseline plasma insulin at 7 days (heating intervention) or 8 weeks (exercise intervention) |