What side effects are associated with this type of intervention?

Resistance exercise training, which enhances insulin sensitivity and muscle function, generally has minimal side effects, primarily involving muscle soreness and fatigue. Pharmacological treatments for insulin resistance include thiazolidinediones (e.g., rosiglitazone), which can cause weight gain, edema, and increased risk of fractures; metformin, which may lead to gastrointestinal issues like nausea and diarrhea; and GLP-1 receptor agonists, which can cause gastrointestinal side effects and, in rare cases, pancreatitis. Each treatment option should be discussed with a healthcare provider to tailor the approach to the individual's needs and health status.

What prior FDA approvals exist?

FDA-approved treatments for insulin resistance that have mechanisms similar to those being studied in resistance exercise training include thiazolidinediones like pioglitazone and rosiglitazone, which act as PPAR gamma agonists to enhance glucose uptake in muscle and adipose tissue. Additionally, GLP-1 receptor agonists such as liraglutide and semaglutide improve insulin sensitivity and promote weight loss, indirectly aiding glucose metabolism.

What other types of research exist?

Promising alternatives to resistance exercise training for insulin-resistant patients include: 1) AMPK agonists like AICAR, which have been shown to enhance metabolic gene expression and improve endurance even in sedentary individuals. 2) GLP-1 receptor agonists, which improve endothelial function and reduce proinflammatory pathways. 3) SGLT2 inhibitors, which lower glucose levels and have cardiovascular benefits. These alternatives target metabolic pathways and can potentially improve glucose metabolism and muscle function.

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Resistance Exercise for Insulin Resistance

Q: What is the mechanism of action of this treatment?

Common treatments for insulin resistance, such as pioglitazone and resistance exercise training, work by improving glucose metabolism and muscle function. Pioglitazone reduces lipid deposition in skeletal muscle and increases the expression of genes like p-ACC, GLUT7, PGC-1α, and CPT1, which are involved in the AMPK signaling pathway. This helps in regulating glucose levels and enhancing insulin sensitivity. Resistance exercise training upregulates PGC-1a4 and PPARB; genes, which facilitate glucose storage and utilization in muscles, improve muscle mass, and reduce oxidative stress. These mechanisms are crucial for insulin resistance patients as they help in maintaining better glycemic control and overall metabolic health.

N/A

Recruiting

Led By K Sreekumaran Nair

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

hip to waist ratio of >0.85 in women and 1.0 in men

hip to waist ratio of <0.76 in women and 0.90 in men

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and after 3 months

Awards & highlights

Study Summary

This trial will investigate how resistance exercise training can improve insulin resistance, muscle loss, and performance by studying two genes.

Who is the study for?

This trial is for people aged 50-75 with obesity (BMI 30-38) and insulin resistance, indicated by fasting glucose levels of ≥100-140 mg/dl. Participants should not be on certain medications like beta blockers or anti-hyperglycemic drugs, including metformin, and must not have a history of alcohol/drug abuse or significant medical conditions that could interfere with the study.Check my eligibility

What is being tested?

The trial is testing how resistance exercise training can improve muscle mass, performance, and insulin sensitivity in those who are insulin resistant. It will explore if this type of exercise affects two specific genes believed to help muscles use glucose better and reduce oxidative stress.See study design

What are the potential side effects?

Resistance exercise generally has minimal side effects but may include muscle soreness, fatigue, or injury if not performed correctly. The risk increases for individuals with pre-existing health conditions; however, these risks will be managed under supervision in the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My hip to waist ratio is above 0.85 (if I am a woman) or 1.0 (if I am a man).

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My hip to waist ratio is below the required threshold.

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I am between 50 and 75 years old.

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My BMI is between 30 and 38.

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My hip to waist ratio is below the required threshold for my gender.

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I am between 50 and 75 years old.

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My hip to waist ratio is above 0.85 (if I am a woman) or 1.0 (if I am a man).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and after 3 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and after 3 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and after 3 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Change in PGC1a Expression

Change in PPARb Expression

Change in Protein degradation

Secondary outcome measures

Change in Glycogen Content

Change in Glycogen Synthase

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Insulin Resistant Exercise GroupExperimental Treatment1 Intervention

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).

Group II: Insulin Resistant Control GroupActive Control1 Intervention

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

Group III: Insulin Sensitive Lean GroupActive Control1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Resistance Exercise

2017

Completed Phase 4

~880

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for insulin resistance, such as pioglitazone and resistance exercise training, work by improving glucose metabolism and muscle function. Pioglitazone reduces lipid deposition in skeletal muscle and increases the expression of genes like p-ACC, GLUT7, PGC-1α, and CPT1, which are involved in the AMPK signaling pathway. This helps in regulating glucose levels and enhancing insulin sensitivity. Resistance exercise training upregulates PGC-1a4 and PPARB; genes, which facilitate glucose storage and utilization in muscles, improve muscle mass, and reduce oxidative stress. These mechanisms are crucial for insulin resistance patients as they help in maintaining better glycemic control and overall metabolic health.

Effect of pioglitazone on skeletal muscle lipid deposition in the insulin resistance rat model induced by high fructose diet under AMPK signaling pathway.Fuzhu jiangtang granules combined with metformin reduces insulin resistance in skeletal muscle of diabetic rats via PI3K/Akt signaling.Expression of the splice variants of the p85alpha regulatory subunit of phosphoinositide 3-kinase in muscle and adipose tissue of healthy subjects and type 2 diabetic patients.