Exercise for Insulin Resistance in Type 2 Diabetes

(EXPET Trial)

Overseen By Recruitment Department

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

Must not be taking: Insulin, Incretin mimetics, Thiazolidinediones, others

Disqualifiers: Renal, Cardiac, Liver, Lung, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how exercise affects insulin resistance in people with Type 2 Diabetes, focusing on changes in muscle and fat tissue. Participants will undergo tests, including muscle and adipose tissue biopsies, to assess how exercise might enhance the body's response to insulin. It suits individuals with Type 2 Diabetes who do not exercise regularly and are not on insulin or multiple diabetes medications. As an unphased trial, this study provides a unique opportunity to contribute to understanding the benefits of exercise in diabetes management.

Will I have to stop taking my current medications?

The trial requires that you are not currently taking insulin, injectable incretin mimetics, thiazolidinediones, or more than two glucose-lowering medications. You also cannot be on certain medications like blood thinners, anti-inflammatory drugs, or beta-blockers. If you are on these medications, you may need to stop them to participate.

What prior data suggests that these methods are safe for participants?

Research has shown that taking small samples of fat or muscle tissue is generally safe. For fat tissue samples, one study found that almost half required only one needle insertion, indicating a simple process with minimal discomfort. Minor issues like bruising may occur, but serious problems are rare.

Muscle tissue samples are also considered low-risk. Bruising and discomfort at the site may occur, but these are usually mild. Complications such as muscle damage are uncommon. Overall, these procedures are well-tolerated and have been safely used in many research studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how exercise impacts insulin resistance in people with Type 2 diabetes by examining changes in adipose and muscle tissue. Unlike standard treatments, which often involve medications like metformin or insulin injections, this approach looks at how physical activity might directly influence the body's tissues at a cellular level. By conducting adipose and muscle biopsies, scientists hope to uncover new insights into how exercise can improve insulin sensitivity and potentially offer a complementary or alternative strategy to traditional drug therapies. This could lead to more personalized and effective management of Type 2 diabetes.

What evidence suggests that exercise could be an effective treatment for insulin resistance in Type 2 Diabetes?

Research has shown that exercise can lower insulin resistance in people with Type 2 Diabetes (T2D). A 12-week structured exercise program significantly reduces insulin resistance and improves quality of life. Studies also find that strength training boosts muscle strength, lowers blood pressure, and improves cholesterol levels. High-intensity interval training (HIIT) helps control blood sugar and fat levels in people with T2D. Overall, exercise programs have proven effective in managing insulin resistance in T2D. ^{6 7 8 9 10}

Who Is on the Research Team?

Bret Goodpaster, PhD

Principal Investigator

Scientific Director | Senior Investigator

Are You a Good Fit for This Trial?

This trial is for adults aged 30-65 with Type 2 Diabetes who are sedentary, have a BMI of 25-45 kg/m2, and haven't had significant weight changes recently. They must not be on more than two glucose-lowering medications or insulin and should be free from major diseases or conditions that could interfere with the study.

Inclusion Criteria

I am between 30 and 65 years old.

Sedentary (1 day or less per week of structured exercise)

I have type 2 diabetes.

Exclusion Criteria

Resting blood pressure ≥ 160/100 mm Hg

Triglycerides ≥ 500 mg/dL

I have not had major surgery on my abdomen, pelvis, or legs in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exercise Intervention

Participants undergo exercise training to assess effects on skeletal muscle and adipose tissue insulin resistance

Duration not specified

Assessment

Muscle glucose uptake is assessed pre and post exercise intervention using PET imaging and hyperinsulinemic euglycemic clamp

24 hours

Follow-up

Participants are monitored for safety and effectiveness after the exercise intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adipose Tissue Biopsy
• Exercise Testing (VO2max)
• Hyperinsulinemic euglycemic clamp
• Maximal ATP Production (ATPmax)
• Muscle Biopsy
• PET imaging

Trial Overview

The study tests how exercise affects insulin resistance in people with Type 2 Diabetes by using PET imaging, muscle and fat biopsies, and measuring maximum ATP production. Participants will undergo an exercise regimen to see if it improves their condition.

How Is the Trial Designed?

Group I: All Participants Experimental Treatment 6 Interventions

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

A review of 496 muscle biopsies from 274 subjects (168 healthy and 106 chronically ill) found that adverse events from percutaneous muscle biopsy are rare, with the most common issues being mild pain, erythema, and ecchymosis occurring at a rate of 1.27%.

The incidence of complications did not differ significantly between healthy individuals and those with chronic illnesses, suggesting that the procedure is safe and has minor clinical relevance for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects. Neves, M., Barreto, G., Boobis, L., et al.[2012]

In a study of 28 participants (14 young lean offspring of type 2 diabetic parents and 14 healthy controls), it was found that those at high risk for diabetes exhibited insulin resistance and increased intramyocellular triglyceride content in specific muscles, despite having normal fat distribution.

The research highlighted that intramyocellular triglyceride levels in the soleus muscle and plasma free fatty acid levels are significant predictors of whole body insulin sensitivity, suggesting that these measurements could help monitor lipid metabolism abnormalities in prediabetic states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Perseghin, G., Scifo, P., De Cobelli, F., et al.[2022]

A systematic review and meta-analysis of 11 studies involving 846 participants demonstrated that structured exercise interventions significantly reduced fasting insulin levels in individuals with type 2 diabetes mellitus (T2DM).

The analysis indicates that exercise also led to improvements in fasting blood sugar levels, suggesting that structured exercise can effectively enhance insulin sensitivity and manage T2DM, providing moderate evidence for its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis. Sampath Kumar, A., Maiya, AG., Shastry, BA., et al.[2019]

Exercise training in adults with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT) leads to beneficial adaptations in skeletal muscle, including increased muscle fiber area, capillary density, and improved expressions of glycogen and GLUT4 proteins.

The review highlighted a lack of robust randomized controlled trials with muscle biopsy data, indicating a need for more comprehensive studies to explore the insulin signaling pathway and its role in enhancing insulin sensitivity and glucose regulation through exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review. Wang, Y., Simar, D., Fiatarone Singh, MA.[2018]

Subcutaneous adipose tissue can be safely and efficiently obtained in a non-clinical setting using a specific biopsy technique, allowing researchers to study metabolic conditions with accessible samples.

The technique is safe for participants, allowing them to resume most activities shortly after the procedure, and enables the collection of sufficient tissue for research, including the possibility of two biopsies in one day for before-after studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Subcutaneous Adipose Tissue Sampling using a Mini-liposuction Technique. MacGregor, KA., Rodriguez-Sanchez, N., Barwell, ND., et al.[2021]

The study compared three methods for measuring adipose tissue insulin sensitivity in 25 adults, finding that the Adipo-IR index and the one-step hyperinsulinemic-euglycemic clamp are reliable predictors of insulin sensitivity, correlating well with the gold standard multistep pancreatic clamp technique.

Age and physical fitness were significant factors influencing the accuracy of these measurements, indicating that while Adipo-IR is useful for larger studies, the multistep pancreatic clamp may be necessary for detailed mechanistic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to Measure Adipose Tissue Insulin Sensitivity. Søndergaard, E., Espinosa De Ycaza, AE., Morgan-Bathke, M., et al.[2022]

Skeletal muscle plays a crucial role in insulin resistance, particularly in conditions like obesity and type 2 diabetes, where it exhibits various metabolic abnormalities affecting glucose and lipid metabolism.

Exercise training has been shown to improve these muscular abnormalities and is beneficial for managing insulin resistance, but individualized exercise prescriptions are necessary due to variability in responses and conflicting results on glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise. Pérez-Martin, A., Raynaud, E., Mercier, J.[2019]

A new mini-liposuction technique allows for the safe and efficient removal of larger adipose tissue samples (3-15 g) from obese patients with minimal scarring and quick recovery, compared to traditional open surgical biopsies.

The procedure maintains the viability of isolated adipocytes, which can effectively transport glucose, making it suitable for extensive assays in research on adipose tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous adipose tissue biopsy by mini-liposuction for metabolic studies. Bastard, JP., Cuevas, J., Cohen, S., et al.[2017]

In a study of 75 middle-aged and older adults with overweight or obesity, higher levels of intermuscular adipose tissue (IMAT) were linked to increased fasting glucose levels and insulin resistance, suggesting a potential risk factor for metabolic issues.

The saturation of intramyocellular lipids (IMCL) was also positively associated with fasting glucose concentration, indicating that both IMAT and IMCL saturation may contribute to insulin resistance in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermuscular Adipose Tissue Content and Intramyocellular Lipid Fatty Acid Saturation Are Associated with Glucose Homeostasis in Middle-Aged and Older Adults. Kim, JE., Dunville, K., Li, J., et al.[2022]

In a study of 66 patients who underwent repeat muscle biopsies, 24% received a definitive diagnosis that changed their management, highlighting the potential importance of this procedure in diagnosing myopathy.

Additionally, 45% of repeat biopsies provided clinically useful information, such as ruling out other conditions or confirming previous diagnoses, which can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of repeat skeletal muscle biopsy: how useful is it? Goutman, SA., Prayson, RA.[2018]

In a study of 461 older men, higher levels of circulating adiponectin were associated with increased capillary density and a higher proportion of type I muscle fibers, which are linked to better insulin sensitivity.

Adiponectin appears to partially mediate the relationship between muscle morphology and insulin sensitivity, suggesting that improving muscle structure could enhance metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity. Ingelsson, E., Arnlöv, J., Zethelius, B., et al.[2012]

In a study of 18 older men, both central abdominal fat and the lipid content in skeletal muscle were found to independently predict insulin sensitivity, indicating that both factors play a significant role in insulin action.

The research suggests that the relationship between central fat and insulin resistance may involve circulating factors, such as leptin, rather than a direct link between fat accumulation in the muscle and central fat stores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent influences of central fat and skeletal muscle lipids on insulin sensitivity. Furler, SM., Poynten, AM., Kriketos, AD., et al.[2011]

In a study of 44 women with type 2 diabetes over 12 weeks, resistance exercise led to a significant reduction in retinol-binding protein-4 (RBP4), which is associated with insulin sensitivity, but did not improve insulin sensitivity or alter muscular adipose tissue levels.

Both resistance and aerobic exercise resulted in significant decreases in body mass index and waist circumference, indicating that while exercise is beneficial for weight management, it may not directly impact muscle fat or insulin sensitivity in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. Ku, YH., Han, KA., Ahn, H., et al.[2022]

In a study of 79 obese adults, those with type 2 diabetes and peripheral neuropathy (T2DMPN) had significantly higher intermuscular adipose tissue (IMAT) and lower subcutaneous adipose tissue (SQAT) compared to controls, indicating a detrimental shift in fat distribution.

Higher IMAT volumes were linked to poorer muscle performance and physical function, suggesting that increased IMAT may negatively impact mobility and strength in individuals with T2DMPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy. Bittel, DC., Bittel, AJ., Tuttle, LJ., et al.[2022]

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