Molecular Mechanisms of Exercise Benefits to Insulin Resistant People

NCT04158375 | Completed Results

• 2 other identifiers: 19-0062731R01AG062859-01A1
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 3

Brief Summary

This proposal will investigate the underlying mechanisms of enhanced insulin sensitivity and improvement of muscle loss and performance in insulin resistant people by resistance exercise training. Based on the investigator's preliminary data, they hypothesize that the key regulators of health benefits of resistance training are two genes: PGC-1a4 and PPARB;, and that the increased expression of these genes following resistance training facilitates storage of glucose in muscle and enhances its utilization for the energy need of muscle for contraction as well as enhancing muscle mass and performance. The investigators will also determine whether resistance training can reduce the higher oxidative stress in insulin resistant humans and improve their muscle protein quality.

Conditions

Insulin Resistance; Obesity

Keywords

Resistance Exercise

Outcome Measures

Primary Outcomes (3)

• Change in Muscle Strength

  Change in 1RM normalized to lean mass

  Baseline and 3 Months

• Change in Insulin Sensitivity

  Difference from baseline and 3 months of the insulin area on under the curve - A measure of insulin sensitivity as measured during an oral meal tolerance test - Time points (-20, 0, 10, 20, 30, 60, 90, 150, 240 minutes)

  Baseline and 3 Months

• Change in Lean Mass

  Change in body lean mass as measured by DEXA scan

  Baseline and 3 months

Secondary Outcomes (1)

• Change in Fat Percentage

  Baseline and 3 Months

Study Arms (3)

Insulin Resistant Exercise Group

EXPERIMENTAL

Resistance (RE) training will be performed 4 days per week using a combination of upper and lower body exercises at 8-12 repetitions per set. Resistance training will be performed using a combination of upper and lower body exercises using machine and free weights. Upper body exercises are chest press, incline press, seated row, lat pull down, triceps extension, biceps curl and lateral raises. Major muscle groups for upper body exercises will include chest (pectoralis major and minor), arm (biceps and triceps), shoulder (deltoids) and back (latissimus dorsi and rhomboids). Lower body exercises are leg press, lunge (with body weight progressing to dumbbells), seated leg extension, seated leg curl, calf raises and abdominal crunches. Major muscle groups for the lower body exercises will be thighs (quadriceps and hamstrings), calves (gastrocnemius and soleus) and core (rectus abdominus and obliques).

Behavioral: Resistance Exercise

Insulin Resistant Control Group

NO INTERVENTION

Participants in this group will perform no exercise for the 3 month study period.

Insulin Sensitive Lean Group

NO INTERVENTION

Participants in this group will have a baseline study for comparison to the insulin resistant groups.

Interventions

Resistance Exercise BEHAVIORAL

Resistance (RE) training will be performed 4 days per week using a combination of upper and lower body exercises at 8-12 repetitions per set. Participants will complete 2 progressing to 4 sets of 8 to 12 repetitions per exercise, with 1 minute rest between sets. Participants will warmup for 5 minutes on a treadmill, cycle ergometer or elliptical at \~50% VO2 peak then begin resistance training. Resistance will be performed 4 days per week with lower body exercise on Monday and Thursday, and upper body on Tuesday and Friday. Wednesdays are a rest day. Participants will begin at 2 sets per exercise on weeks 1 and 2, then 3 sets for week 3, and 4 sets for weeks 4 to 12.

Insulin Resistant Exercise Group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 50-75yrs
• BMI 30-38kg/m2
• hip to waist ratio of \>0.85 in women and 1.0 in men
• fasting glucose ≥100-140mg/dl
• Lean Group
• age 50-75 years
• hip to waist ratio of \<0.76 in women and 0.90 in men
• fasting glucose of \<100mg/dl.

You may not qualify if:

• Coronary artery disease or heart failure.
• Participation in a structured exercise program \>2 days per week
• A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
• Inpatient psychiatric treatment in the past 6 months
• Presence of a known adrenal disorder
• Abnormal liver function test results (Transaminase \>2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
• Abnormal renal function test results (calculated GFR \<60 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
• Active gastroparesis
• If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
• Uncontrolled thyroid disease (TSH undetectable or \>10 mlU/L); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise
• Abuse of alcohol or recreational drugs
• Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis).
• Uncontrolled arterial hypertension (Resting diastolic blood pressure \>90 mmHg and/or systolic blood pressure \>160 mmHg) at the time of screening.
• Oral steroids
• A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute on Aging (NIA): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Pataky MW, Heppelmann CJ, Sevits KJ, Asokan AK, Kumar AP, Klaus KA, Dasari S, Kunz HE, Strub MD, Robinson MM, Coon JJ, Lanza IR, Adams CM, Nair KS. Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle. Nat Commun. 2025 Jul 1;16(1):5700. doi: 10.1038/s41467-025-60049-0.

  PMID: 40595512 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Insulin Resistance; Obesity

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Limitations and Caveats

There are no limitations or caveats at this time.

Results Point of Contact

• Title: Dr. Sreekumaran Nair - Principal Investigator
• Organization: Mayo Clinic

nair.sree@mayo.edu

507-284-2511

Study Officials

• K Sreekumaran Nair

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Division of Endocrinology

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 8, 2019
• Study Start: September 2, 2020
• Primary Completion: September 17, 2024
• Study Completion: September 30, 2024
• Last Updated: November 25, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)