Weight Loss and Exercise for Insulin Resistance in Aging

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

Disqualifiers: Cardiovascular disease, Peripheral vascular, Hepatic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how weight loss and exercise can improve insulin resistance and muscle health in older adults. Participants will engage in either an exercise program or a weight loss plan (energy restriction-induced weight loss) to assess the effects on metabolic health. The study seeks individuals struggling with obesity (BMI of 30 or more) who lead a mostly sedentary lifestyle, with no more than one exercise session per week.

As an unphased trial, this study offers a unique opportunity to contribute to valuable research that could enhance health outcomes for many.

Will I have to stop taking my current medications?

If you have diabetes, you will need to stop taking your diabetes medication for 14 days before the trial starts. This is called a washout period. For other medications, the trial protocol does not specify if you need to stop taking them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both cutting calories and exercising are generally safe and well-tolerated ways to help the body use insulin more effectively. Cutting calories can quickly improve food processing, even before weight loss occurs, enhancing insulin use without serious side effects.

Exercise, particularly strength training, is also safe and effective. It helps older adults improve insulin sensitivity and reduces insulin resistance, a condition where the body doesn't respond well to insulin. Studies indicate that strength training is safe for individuals with or without heart issues.

Overall, these methods are well-tolerated, with studies supporting their safety and effectiveness in improving insulin use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the approach of combining energy restriction-induced weight loss and exercise to tackle insulin resistance in aging because it addresses the condition from multiple angles. Unlike standard treatments that often focus solely on medication to manage insulin levels, this method emphasizes lifestyle changes that can lead to sustainable results. The energy restriction component helps reduce excess body weight, a key factor in insulin resistance, while exercise enhances insulin sensitivity and overall metabolic health. This dual approach not only targets the root causes of insulin resistance but also promotes overall well-being, offering a holistic alternative to conventional drug-based therapies.

What evidence suggests that this trial's treatments could be effective for insulin resistance?

This trial will compare the effects of energy restriction-induced weight loss and exercise on insulin resistance in aging. Research has shown that both calorie reduction and exercise can improve insulin resistance. Participants in the energy restriction-induced weight loss arm may improve insulin use by losing weight through calorie reduction. Meanwhile, those in the exercise training protocol arm may enhance insulin use through activities like strength training, which also helps control blood sugar and build muscle strength. Together, these approaches may help manage insulin resistance in aging muscles. ^{1 6 7 8 9}

Who Is on the Research Team?

Bret Goodpaster, PhD

Principal Investigator

Translational Research Institute for Metabolism and Diabetes

Are You a Good Fit for This Trial?

The MIRAGE study is for older adults aged 65-80 who are overweight, sedentary, non-smokers with stable weight and blood pressure within certain limits. Those with diabetes must be able to monitor their own blood sugar after stopping medication for two weeks. People with recent heart attacks, vascular diseases, neuropathy or serious liver, kidney or muscle conditions cannot join.

Inclusion Criteria

Your blood pressure should be below 150/95 mmHg when measured at rest.

Your weight has not changed by more than 10 pounds in the past 6 months.

You do not engage in regular exercise, meaning you do not exercise at least once a week.

Exclusion Criteria

I do not have active liver, kidney, muscle, or blood cancer conditions.

Weak pulse that a doctor can feel

You have abnormal sounds in your legs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline measurements of muscle strength and power using a short physical performance battery, knee extension, and muscle power testing

1 day

Visit 2 (baseline)

Treatment

Participants undergo diet-induced weight loss with or without exercise to study effects on mitochondrial biogenesis, cellular redox state, and insulin resistance

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including insulin sensitivity and intramyocellular lipid measurements

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Energy Restriction-Induced Weight Loss
• Exercise

Trial Overview This trial investigates how energy restriction-induced weight loss and exercise can affect insulin resistance and muscle mass in aging individuals. It aims to uncover factors contributing to metabolic dysfunction in the elderly.

How Is the Trial Designed?

Group I: Exercise training protocol Experimental Treatment 1 Intervention

Group II: Energy restriction-induced weight loss Experimental Treatment 1 Intervention

Group III: Health Education Active Control 1 Intervention

Who Is Running the Clinical Trial?

Translational Research Institute for Metabolism and Diabetes, Florida

Lead Sponsor

Trials

41

Recruited

3,600+

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Published Research Related to This Trial

Most randomized controlled trials (RCTs) show that exercise alone leads to only modest weight loss, and while combining exercise with dietary restriction can enhance weight loss, the energy deficit from exercise is often much smaller than that from diet alone.

High levels of exercise can lead to significant weight loss comparable to caloric restriction, but maintaining such exercise levels can be challenging for overweight or obese individuals, highlighting the importance of physical activity for long-term weight maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of physical activity in producing and maintaining weight loss. Catenacci, VA., Wyatt, HR.[2022]

Combining physical exercise with energy restriction diets leads to greater weight loss than exercise alone, making it the most effective strategy for significant weight loss.

Engaging in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly, along with resistance training, is recommended for weight loss and maintenance, which also helps improve obesity-related health issues like diabetes and cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity and physical exercise. Celik, O., Yildiz, BO.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9071425/

Weight Loss and Exercise Differentially Affect Insulin ... Our findings suggest that weight loss via calorie restriction alone is insufficient to significantly improve skeletal muscle insulin sensitivity and requires ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2161831323013911

Effects of Intermittent Energy Restriction Compared with ... The present systematic review and meta-analysis found that IER was not superior to CER for changes in weight loss, body fat, and other fasting cardiometabolic ...

3. nature.com nature.com/articles/nutd201731

Enhanced insulin sensitivity in successful, long-term weight ... Weight-loss interventions using calorie restriction and/or increased physical activity have shown improvements in insulin sensitivity, with ...

4. academic.oup.com academic.oup.com/biomedgerontology/article/73/1/81/2966367

Calorie Restriction-induced Weight Loss and Exercise Have ... Weight loss induced by moderate calorie restriction (CR) or chronic exercise leads to a significant drop in plasma insulin and improves insulin ...

5. mdpi.com mdpi.com/2072-6643/13/4/1302

Effects of Calorie Restriction on Health Span and Insulin ... VLCKD has been associated with a dramatic reduction in insulin and oral glucose-lowering medication requirements, including total remission of diabetes [44].

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8071299/

Effects of Calorie Restriction on Health Span and Insulin ... In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets.

7. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00632/full

Individual Response Variation in the Effects of Weight Loss ... Current evidence suggests that weight loss induced by decreased energy intake or increased energy expenditure improves insulin sensitivity and ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03264001

Effects of Progressive Negative Energy Balance on ... In fact, negative energy balance induced by calorie restriction can improve metabolic function acutely, i.e. within 1-2 days and before any weight loss occurs.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522032543

Effect of a high-protein, energy-restricted diet on body ... The aim of this study was to compare the effects of 2 isoenergetic, energy-restricted diets with either a high or standard content of dietary protein (27% or 16 ...