ATP Release and Sympathetic Nerve Activity in Patients With Type II Diabetes

Study Overview
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Brief Summary
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Type II diabetes (T2D) is characterized by endothelial dysfunction, resulting in a poor tissue perfusion and function as well as an increased risk of cardiovascular events. ATP, which is released from the red blood cells, contributes to the regulation of the blood flow and studies have shown that red blood cells taken from T2D patients have an impaired ability to release ATP. However, it is not known whether the changes in the ATP system is an underlying cause of the poor tissue perfusion observed in T2D. The purpose of project 1 is to test the hypothesis that the deterioration in blood flow in T2D is caused by a reduced release ATP from red blood cells, and to test if pharmacological manipulation of cAMP will normalize ATP release, plasma ATP levels and thereby blood flow. Furthermore, epidemiological studies show a clear link between regular exercise and a reduced risk of serious cardiovascular disease. The extent to which a physically active lifestyle may improve endothelial function in T2D is unknown. Regular physical activity improves vascularization and induces an anti-inflammatory environment. Both the angiogenic and anti-inflammatory effects of physical activity is in part mediated by substances released from the active muscle. These muscle-derived substances are classified as myokines and have paracrine, autocrine and endocrine effects and may thereby affect distant tissues. The purpose of the project 2 is to investigate whether high intensity interval training may reverse endothelial dysfunction in T2D through increased release of ATP and myokines. In individuals with T2D we will determined blood flow in the muscle tissue using advanced ultrasound. In addition, using intravascular and intramuscular microdialysis we will determine ATP levels in blood and in the muscle interstitium.

Official Title
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ATP Release and Sympathetic Nerve Activity in Patients With Type II Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetics BMI >30 Non smokers Physical Inactive (less than 2 hours per week) Exclusion Criteria: Thyroid disorder Known ischemic heart disease (intermittent claudication, angina) Diabetic eye disease Diabetic kidney disease Known heart disease Intake of beta-blockers Blood Pressure > 140/90 Nephropathy and macroalbuminuria GFR measurement Acute illness within the last three weeks Chronic disease, including cancer, heart (ischemic and claudication), liver, kidney and respiratory disorders (asthma) Significant peripheral diabetic neuropathy (severe sensory disturbances) Significant peripheral diabetic angiopathy (former or current foot ulcer) Rheumatological disorders Pregnancy or childbirth within the past three months Alcohol abuse smokers Use of illegal performance-enhancing drugs (see IAAF list) Injuries and / or surgery within the last 6 months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High intensity exercise<br>3 times per week in a total of 12 weeks | Behavioral: Exercise training<br> <br> |
| Experimental: Low intensity exercise<br>3 times per week in a total of 12 weeks | Behavioral: Exercise training<br> <br> |
| Experimental: Control<br>Normal lifestyle for 12 weeks | Behavioral: Exercise training<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose metabolism |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, High intensity exercise, Glycemic control