A Study to Evaluate Molecular Mechanisms of Exercise Benefits in Insulin Resistant People


About this study

The aim of the study is to investigate the effects of a 3-month resistance exercise program (in people aged 50 to 75) on muscle mass, body composition, muscle strength, brain function and cognition, muscle efficiency processing blood sugar, the body’s ability to build muscle, and fat cells.

Earlier research has shown that exercise has significant benefits in preventing certain diseases and conditions such as diabetes, dementia, heart disease, and more. We also know from other research that resistance exercise (lifting weights) and aerobic exercise (running, biking, walking), improve metabolism through separate ways on the molecular level, also called “molecular pathways.” With new and sophisticated technologies, we can analyze these molecular pathways to learn how exercise improves health. 

The purpose of the study is to understand why resistance exercise can prevent disease though analyzing the ‘molecular pathways’ in correlation with blood sugar to understand its effects on diabetes. We also will correlate these results with brain scan and cognitive tests to understand the mechanisms behind cognitive decline and dementia. 

Participants in this study will undergo a series of baseline measurements including but not limited to blood tests, brain scans, aerobic exercise tests, body composition scans, resistance exercise, a 24-hour research visit, 4 needle muscle biopsies, 2 needle fat biopsies, and an infusion of amino acids (the building blocks of muscles). 

Following the completion of the baseline visits, participants will be randomly placed into a resistance training group or a control group. 
1.    Resistance Training Group: Participants put into the resistance training program will take part in a personalized resistance training program and meet with a personal trainer four times a week for three months. Following the three months of resistance training participants will repeat the baseline visits and will be completed with the study. 
2.    Control Group: Participants put into the control group are asked not to make any lifestyle changes for 3 months. Following the 3 months, they will come back for a repeat of the baseline measurements. At this point they will have the choice to take part in the resistance training program, followed by a third set of baseline measurements. 

Remuneration is provided. 

Study title: Molecular Mechanisms of Exercise Benefits to Insulin Resistant People
IRB #: 19-006273
Principle Investigator: Dr. K Sreekumaran Nair

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Obese, insulin resistant men and women using the following criteria

  • Age 50-75 years.
  • BMI 28-38kg/m^2.
  • Hip-to-waist ratio of > 0.85 in women and > 80cm and > 0.90 in men or > 94cm.
  • Fasting glucose ≥ 100-140mg/dl.

Lean, insulin sensitive men and women

  • Age 50-75 years.
  • Hip-to-waist ratio of < 0.76 in women and 0.90 in men.
  • Fasting glucose of < 100mg/dl. 

Lactate discorder group

  • Invitation from PI.

Exclusion Criteria:

  • 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 < 45 mL/min/1.73m^2); 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.
  • Restrictions on Use of Other Drugs or Treatments:
    • Medications that may impact study end points such as mitochondrial biology; e.g.. beta blockers;
    • Anti-hyperglycemic drugs including metformin;
    • Any other medication that the investigator believes is a contraindication to the subject’s participation.

Eligibility last updated 5/4/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

K Nair, M.D., Ph.D.

Open for enrollment

Contact information:

Frederick de Ruiter



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