Physical Activity and Obesity

Study Overview
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Brief Summary
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The purpose of the study is to see if a twelve-week exercise intervention in overweight or obese subjects with pre-diabetes or early disease course type 2 diabetes can lead to improved skeletal muscle capillary blood flow by improving substances that dilate blood vessels and result in improved insulin sensitivity.

Official Title
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Physical Activity and Obesity: The Role of Nitric Oxide and Eicosanoids in Regulating Capillary Perfusion and Vascular Insulin Resistance

Conditions
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Sedentary Lifestyle, Obesity, Prediabetic State

Intervention / Treatment
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* Behavioral: High Activity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ages 30-60 years of age Overweight and Obese (28< BMI <45) Confirmed pre-diabetic (5.7≤ HbA1c < 6.5) Type 2 DM, Diagnosis 2 years or less, on no medications or metformin only, HbA1c ≤ 6.7 Exclusion Criteria: Stage 3 chronic kidney disease (glomerular filtration rate [GFR] < 60) Obstructive Coronary artery disease Congestive heart failure (ejection fraction < 55%) Peripheral vascular disease, Degenerative joint disease, musculoskeletal disease, or peripheral vascular disease that limits ability to exercise Know hypersensitivity to Definity® ultrasound contrast agent Intra-cardiac or pulmonary shunt The use of antithrombotic agents or a severe bleeding diathesis due to risk of bleeding with intravenous and arterial line placement Physical activity greater than three hours per week Pregnancy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Activity Group<br>Subject randomized to High Activity group will have 36, one hour training sessions over 12 weeks. | Behavioral: High Activity<br>* The high activity group will undergo a 12 week ramped exercise protocol.<br>|
| No Intervention: Standard of Care Group<br>The standard of care group will maintain their baseline level of activity for 12 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin mediated skeletal muslce blood flow and capillary recruitment | Contrast enhanced ultrasound skeltal muscle perfusion imaging will be performed at rest and during glucose steady state infusion during an insulin clamp. The change in blood flow will be determined between the resting state and at peak steady state to determine the absolute increase in skeletal muslce blood flow (ml/min/g) as well as the absolute increase in capillary blood volume (ml/g) of tissue | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of endothelial derived Vasodilators | To quantify the changes in endothelial derived vasodilators. For this aim nitric oxide bioavailability as tested by flow mediated vasodilation will be performed and reported as absolute change (cm) and percent change (%) in brachial artery diameter from baseline to post ischemic occlusion of the forearm. Plasma samples for eicosanoids will be collected and assessed by liquid chormatography/mass spectroscopy to to assess changes in endothelial derived vasodilators. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Prediabetic State, Sedentary Lifestyle, Insulin Resistance, Endothelium, Eicosanoids, Nitric Oxide, Regional Blood Flow