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

Trial Summary

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 data supports the effectiveness of the treatment Exercise for Insulin Resistance in Type 2 Diabetes?

Research shows that insulin resistance is linked to the amount of fat stored in muscles and around the abdomen. Improving muscle function and reducing fat content through exercise can enhance insulin sensitivity, which is how well the body responds to insulin. ^{1 2 3 4 5}

Is the exercise treatment for insulin resistance in type 2 diabetes safe?

The procedures involved in the study, such as adipose tissue biopsy and muscle biopsy, are generally safe. Adipose tissue biopsy using a mini-liposuction technique is safe with minimal restrictions on activities post-procedure. Muscle biopsy has a low incidence of minor side effects like pain and bruising, with no significant difference in safety between healthy and chronically ill individuals. ^{5 6 7 8 9}

How does the treatment of adipose and muscle biopsy differ from other treatments for insulin resistance in type 2 diabetes?

Adipose and muscle biopsies are unique because they are not treatments themselves but diagnostic procedures that help researchers understand how exercise affects insulin resistance in type 2 diabetes. Unlike medications or lifestyle changes, these biopsies provide direct insights into the cellular and metabolic changes in muscle and fat tissue, which can guide more personalized treatment strategies. ^{10 11 12 13 14}

What is the purpose of this trial?

The overall aim of this pilot study is to investigate the effects of exercise training on skeletal muscle and adipose tissue insulin resistance in subjects with Type 2 Diabetes (T2D).

Research Team

Bret Goodpaster, PhD

Principal Investigator

Scientific Director | Senior Investigator

Eligibility Criteria

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

Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Korea (South) 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Role of repeat skeletal muscle biopsy: how useful is it? [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity. [2012]

4. United States pubmed.ncbi.nlm.nih.gov

Independent influences of central fat and skeletal muscle lipids on insulin sensitivity. [2011]

5. United States pubmed.ncbi.nlm.nih.gov

Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Human Subcutaneous Adipose Tissue Sampling using a Mini-liposuction Technique. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Percutaneous adipose tissue biopsy by mini-liposuction for metabolic studies. [2017]

8. Denmark pubmed.ncbi.nlm.nih.gov

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects. [2012]

9. United States pubmed.ncbi.nlm.nih.gov

How to Measure Adipose Tissue Insulin Sensitivity. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis. [2019]

11. England 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. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise. [2019]

13. England 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. [2022]

14. United States 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. [2022]