Obesity, Prediabetic State, Sedentary Lifestyle
Conditions
Keywords
Obesity, Prediabetic State, Sedentary Lifestyle, Insulin Resistance, Endothelium, Eicosanoids, Nitric Oxide, Regional Blood Flow
Brief summary
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.
Interventions
BEHAVIORALHigh Activity
The high activity group will undergo a 12 week ramped exercise protocol.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females ages 30-60 years of age 2. Overweight and Obese (28\< BMI \<45) 3. Confirmed pre-diabetic (5.7≤ HbA1c \< 6.5) 4. Type 2 DM, Diagnosis 2 years or less, on no medications or metformin only, HbA1c ≤ 6.7
Exclusion criteria
1. Stage 3 chronic kidney disease (glomerular filtration rate \[GFR\] \< 60) 2. Obstructive Coronary artery disease 3. Congestive heart failure (ejection fraction \< 55%) 4. Peripheral vascular disease, 5. Degenerative joint disease, musculoskeletal disease, or peripheral vascular disease that limits ability to exercise 6. Know hypersensitivity to Definity® ultrasound contrast agent 7. Intra-cardiac or pulmonary shunt 8. The use of antithrombotic agents or a severe bleeding diathesis due to risk of bleeding with intravenous and arterial line placement 9. Physical activity greater than three hours per week 10. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin mediated skeletal muslce blood flow and capillary recruitment | 3 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of endothelial derived Vasodilators | 3 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correalte changes in fitness to vasodilators, blood flow, and insulin sensitivity | 3 months | Aim 3. To correlate changes in fitness as measured by peak VO2 and anaerobic threshold during cardiopulmonary exercise testing with changes in endothelial derived vasodilators, skeletal muscle blood flow, and insulin sensitivity. |
Countries
United States
Outcome results
None listed