Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes

NCT04754581 | Active Not Recruiting

• 1 other identifier: 1581803
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

• Individual steps of muscle glucose uptake (pre-exercise)

  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.

  24 hours

• Individual steps of muscle glucose uptake (post-exercise)

  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.

  24 hours

Study Arms (1)

All Participants

OTHER

Other: Maximal ATP Production (ATPmax); Other: Exercise Testing (VO2max); Procedure: Muscle Biopsy; Procedure: Adipose Tissue Biopsy; Other: Hyperinsulinemic euglycemic clamp; Other: PET imaging

Interventions

Maximal ATP Production (ATPmax) OTHER

ATPmax will be measured in order to determine in vivo mitochondrial capacity. The magnetic resonance scans to measure mitochondrial energetics will also be performed.

All Participants

Exercise Testing (VO2max) OTHER

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.

All Participants

Muscle Biopsy PROCEDURE

Sample muscle cells from the left leg Vastus Lateralis (thigh) muscle.

All Participants

Adipose Tissue Biopsy PROCEDURE

Sample fat tissue from the abdomen.

All Participants

Hyperinsulinemic euglycemic clamp OTHER

Measurement of insulin sensitivity.

All Participants

PET imaging OTHER

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.

All Participants

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 30-65 years
• Men and women
• Body mass index (BMI) between 25 and 45 kg/m2
• Sedentary (1 day or less per week of structured exercise)
• Type 2 diabetes mellitus determined by self-report or by a fasting glucose \>126mg/dl
• Weight stable (± 2 kg) for prior 3 months
• Willing to commit to the schedule of assessment visits, including the exercise intervention

You may not qualify if:

• Currently taking insulin, injectable incretin mimetics and thiazolidinediones
• Taking more than two glucose-lowering medications
• Resting blood pressure ≥ 160/100 mm Hg
• Triglycerides ≥ 500 mg/dL
• 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
• Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
• Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training
• Pulse check ("Allen test") indicates participant has poor blood flow in the hands
• Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma)
• Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year
• Use of drugs known to affect energy metabolism or body weight: including, but not limited to orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
• Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
• 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.
• New onset (\<3 months on a stable regime) hormone replacement therapy
• Current use of beta-adrenergic blocking agents

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

AdventHealth Translational Research Institute

Orlando, Florida, 32804, United States

Location

Related Links

• Website for AdventHealth Translational Research Institute

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exercise Test; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Bret Goodpaster, PhD

  Scientific Director | Senior Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-site, pre-post design pilot study with no control group.

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 15, 2021
• Study Start: March 30, 2021
• Primary Completion: August 15, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)