Type 2 Diabetes
Conditions
Brief summary
The overall aim of this pilot study is to investigate the effects of exercise training on skeletal muscle and adipose tissue insulin resistance in subjects with Type 2 Diabetes (T2D).
Interventions
OTHERMaximal ATP Production (ATPmax)
ATPmax will be measured in order to determine in vivo mitochondrial capacity. The magnetic resonance scans to measure mitochondrial energetics will also be performed.
OTHERExercise Testing (VO2max)
Aerobic fitness level will be assessed while participant pedals on a stationary bicycle/walk on a treadmill. The volume of oxygen intake and carbon dioxide (CO2) production will be measured.
PROCEDUREMuscle Biopsy
Sample muscle cells from the left leg Vastus Lateralis (thigh) muscle.
PROCEDUREAdipose Tissue Biopsy
Sample fat tissue from the abdomen.
Measurement of insulin sensitivity.
OTHERPET imaging
After an overnight fast, an intravenous catheter will be placed in each arm (one with arterial line for PET infusion, and the other for infusion of insulin, glucose, and 6,6 D2 glucose tracer. FDG-glucose will be injected followed by 90-minute PET scanning of the thigh.
Sponsors
AdventHealth Translational Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a single-site, pre-post design pilot study with no control group.
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 30-65 years 2. Men and women 3. Body mass index (BMI) between 25 and 45 kg/m2 4. Sedentary (1 day or less per week of structured exercise) 5. Type 2 diabetes mellitus determined by self-report or by a fasting glucose \>126mg/dl 6. Weight stable (± 2 kg) for prior 3 months 7. Willing to commit to the schedule of assessment visits, including the exercise intervention
Exclusion criteria
1. Currently taking insulin, injectable incretin mimetics and thiazolidinediones 2. Taking more than two glucose-lowering medications 3. Resting blood pressure ≥ 160/100 mm Hg 4. Triglycerides ≥ 500 mg/dL 5. Any renal, cardiac, liver, lung, or neurological disease that in the opinion of the principal investigator would compromise participant safety or the participants' ability to complete the exercise training protocol 6. Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease) 7. Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training 8. Pulse check ("Allen test") indicates participant has poor blood flow in the hands 9. Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma) 10. Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year 11. Use of drugs known to affect energy metabolism or body weight: including, but not limited to orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc 12. Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures 13. Participant is currently taking anti-inflammatory medication or has had inflammatory medication within 1 week prior to screening (including over the counter formulations: e.g. Aleve, Motrin, Ibuprofen, Naproxen, low dose ASA. 14. New onset (\<3 months on a stable regime) hormone replacement therapy 15. Current use of beta-adrenergic blocking agents 16. Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months 17. Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal) 18. Abnormal blood count/anemia, blood transfusion or blood donation within the last 2 months 19. Current smokers (smoking within the past 3 months prior to screening visit, including any/all tobacco products) 20. Current drug or alcohol abuse/dependence 21. Metal implants (pace-maker, aneurysm clips) based on investigator's judgment at screening 22. Not physically capable of performing the exercise required of the study protocols 23. Plans to be away \>2 weeks in the next 3 months 24. Unable to participate in Magnetic Resonance Imaging (MRI) assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on investigator's judgment at screening. 25. Unable to tolerate MRI or claustrophobia. 26. Nickel allergy 27. Lidocaine allergy 28. Unable or unwilling to communicate with staff or to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Individual steps of muscle glucose uptake (pre-exercise) | 24 hours | Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp. |
| Individual steps of muscle glucose uptake (post-exercise) | 24 hours | Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBret Goodpaster, PhD
Scientific Director | Senior Investigator
Outcome results
None listed