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IntroductiontoResistanceExerciseandInsulinResistanceinTypeIIDiabetes.docx

Introduction to Resistance Exercise and Insulin Resistance in Type II Diabetes

Type II diabetes is a global health issue, primarily driven by insulin resistance, a condition in which the body's cells fail to respond effectively to insulin. This leads to impaired glucose uptake and elevated blood sugar levels, which increases the risk of long-term complications such as cardiovascular disease, neuropathy, and nephropathy. In middle-aged individuals, managing insulin resistance is critical to mitigating these risks. While aerobic exercise has traditionally been recommended for improving glycemic control, recent research has demonstrated the powerful role resistance exercise can play in improving insulin sensitivity and glucose metabolism (Pesta et al., 2017).

Resistance training is shown to enhance glucose transporter protein 4 (GLUT4) expression in skeletal muscle, increase muscle mass, and improve mitochondrial function, all of which are essential for improving glucose uptake and utilization in Type II diabetes patients (Holten et al., 2004). The adaptations that result from resistance exercise, such as reduced oxidative stress and enhanced mitochondrial biogenesis, contribute to improved insulin sensitivity and metabolic health (Pesta et al., 2017).

Purpose of the Study

The purpose of this study is to investigate the effects of resistance exercise on insulin resistance in middle-aged individuals diagnosed with Type II diabetes. Specifically, this study will evaluate how resistance training influences insulin sensitivity, muscle mass, and mitochondrial function in this population. Resistance exercise has the potential to be a powerful tool in combating the progression of insulin resistance by enhancing key cellular mechanisms responsible for glucose metabolism. The study aims to provide detailed insights into how resistance exercise can be incorporated into diabetes management strategies for middle-aged individuals, focusing on improving long-term glycemic control (Pesta et al., 2017).

Hypothesis

Alternative Hypothesis (H1): Resistance exercise will lead to significant improvements in insulin sensitivity in middle-aged individuals with Type II diabetes. These improvements are expected to result from increased muscle mass and enhanced glucose uptake due to upregulation of GLUT4, as well as mitochondrial adaptations that boost oxidative capacity. The study anticipates that chronic resistance training will activate pathways such as the PI3K-Akt-mTOR pathway, which enhances glucose metabolism and muscle hypertrophy. Additionally, resistance exercise is expected to reduce reactive oxygen species (ROS) and improve mitochondrial function, further promoting insulin action and glycemic control (Pesta et al., 2017).

Null Hypothesis (H0): Resistance exercise will not result in significant improvements in insulin sensitivity in middle-aged individuals with Type II diabetes. There will be no observable changes in muscle mass, GLUT4 expression, mitochondrial function, or insulin signaling, and the intervention will not significantly affect glycemic control (Pesta et al., 2017).

Methodology

The study will follow a randomized controlled trial design, recruiting 40 middle-aged individuals diagnosed with Type II diabetes. Participants will be randomly assigned to one of two groups: a resistance exercise group or a control group.

Intervention:

The resistance exercise group will engage in a 12-week resistance training program, with sessions conducted three times per week. Each session will include multi-joint exercises, such as squats, leg presses, chest presses, and rows, performed at 60-75% of each participant’s one-repetition maximum (1RM). Each exercise will be performed for 3 sets of 8-12 repetitions. This regimen is designed to increase muscle hypertrophy, improve mitochondrial function, and enhance insulin sensitivity, based on findings by Pesta et al. (2017). Resistance training has been shown to induce significant molecular adaptations, such as increased GLUT4 expression and improved mitochondrial oxidative capacity, both of which are critical for glucose metabolism (Holten et al., 2004; Pesta et al., 2017). The control group will maintain their usual care, which may include medications and dietary advice, but no structured exercise.

Outcome Measures:

· Primary Outcome: Insulin sensitivity will be assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at baseline and after 12 weeks of intervention. HOMA-IR will provide a measure of insulin resistance by calculating the relationship between fasting glucose and insulin levels.

· Secondary Outcomes: Muscle biopsies will be performed on a subset of participants at baseline and post-intervention to analyze changes in GLUT4 expression and mitochondrial function. Resistance training has been shown to improve mitochondrial content and activity, critical factors in enhancing glucose metabolism in patients with Type II diabetes (Pesta et al., 2017). Mitochondrial oxidative capacity will be assessed using enzyme assays for citrate synthase and mitochondrial DNA content, both markers of mitochondrial health.

· Body Composition: Changes in muscle mass will be measured using dual-energy X-ray absorptiometry (DEXA) scans. Increased muscle mass is hypothesized to play a significant role in improving insulin sensitivity and glucose disposal (Pesta et al., 2017).

Mechanisms of Action:

Based on findings from Pesta et al. (2017), resistance training is expected to improve insulin sensitivity through several mechanisms. First, resistance training increases GLUT4 expression in skeletal muscle, facilitating greater glucose uptake. Additionally, resistance exercise enhances mitochondrial function by promoting mitochondrial biogenesis and reducing oxidative stress, which are both vital for improved glucose metabolism. Chronic resistance training is also known to activate key signaling pathways, including the PI3K-Akt-mTOR pathway, which supports muscle hypertrophy and glucose metabolism. By optimizing these cellular processes, resistance exercise can serve as an effective non-pharmacological intervention to combat insulin resistance in individuals with Type II diabetes.

Conclusion

This study aims to contribute to the growing body of evidence supporting resistance exercise as an effective intervention for improving insulin sensitivity in middle-aged individuals with Type II diabetes. By focusing on the molecular mechanisms involved in glucose uptake, mitochondrial function, and insulin signaling, the study will provide valuable insights into how resistance training can help manage insulin resistance. If the hypothesis is supported, resistance exercise could play a critical role in diabetes management strategies, particularly for those who prefer or require an alternative to pharmacological interventions (Pesta et al., 2017).

References

Pesta, D. H., Goncalves, R. L. S., Madiraju, A. K., Strasser, B., & Sparks, L. M. (2017). Resistance training to improve type 2 diabetes: working toward a prescription for the future. Nutrition & Metabolism, 14(24). https://doi.org/10.1186/s12986-017-0173-7

Holten, M. K., Zacho, M., Gaster, M., Juel, C., Wojtaszewski, J. F., & Dela, F. (2004). Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with Type 2 diabetes. Diabetes, 53(2), 294 305. https://doi.org/10.2337/diabetes.53.2.294

Colberg, S. R., Sigal, R. J., Yardley, J. E., Riddell, M. C., Dunstan, D. W., Dempsey, P. C., Horton, E. S., Castorino, K., & Tate, D. F. (2016). Physical activity/exercise and diabetes: A position statement of the American Diabetes Association. Diabetes Care, 39(11), 2065-2079. https://doi.org/10.2337/dc16-1728

Castaneda, C., Layne, J. E., Munoz-Orians, L., Gordon, P. L., Walsmith, J., Foldvari, M., Roubenoff, R., Tucker, K. L., & Nelson, M. E. (2002). A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with Type 2 diabetes. Diabetes Care, 25(12), 2335-2341. https://doi.org/10.2337/diacare.25.12.2335

Church, T. S., Blair, S. N., Cocreham, S., Johannsen, N., Johnson, W., Kramer, K., Myers, V., Nauta, M., Rodarte, R. Q., Earnest, C. P., Thompson, A. M., & Sparks, L. (2010). Effects of aerobic and resistance training on hemoglobin A1c levels in patients with Type 2 diabetes: A randomized controlled trial. JAMA, 304(20), 2253-2262. https://doi.org/10.1001/jama.2010.1710

Romero-Arenas, S., Martinez-Pascual, M., & Alcaraz, P. E. (2013). Impact of resistance circuit training on neuromuscular, cardiorespiratory, and body composition adaptations in the elderly. Aging Disease, 4(5), 256-263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794789/

Bacchi, E., Negri, C., Zanolin, E., Milanese, C., Faccioli, N., Trombetta, M., Zoppini, G., Cevese, A., Bonora, E., & Moghetti, P. (2012). Metabolic effects of aerobic training and resistance training in Type 2 diabetic subjects: A randomized controlled trial (the RAED2 study). Diabetes Care, 35(4), 676-682. https://doi.org/10.2337/dc11-1655

Yki-Järvinen, H., & Koivisto, V. A. (1983). Effects of body composition on insulin sensitivity. Diabetes, 32(11), 965-969. https://doi.org/10.2337/diabetes.32.11.965

3415_ExamplePresentation.pdf

Adaptive training prescriptions for neuromuscular diseases

MATTHEW FIEDLER – 1001487526 – KINE 3415

Overview • Rationale

• The Problem

• Our Hypothesis

• Key Terms

• Review of the Literature

• Summary and Conclusion

Christina’s World, by American artist Andrew Wyeth in 1948

Depicts Anna Christina Olson, a woman with CMT, crawling across a field. Wyeth knew her personally and would regularly paint her, often highlighting the disease indirectly. Notice the atrophy in the arms. Credit: MoMA Alfred H Barr, Jr Gallery, 16.1949

Rationale •Exercise is a key part of a healthy lifestyle, some benefits include; • Decreased risk of CVD, obesity, diabetes, cancers, depression, & anxiety • Improved effectiveness of therapies targeting those diseases

•However, neuromuscular diseases (NMDs) make exercise a challenge for the patient and healthcare provider alike

•Thus, adaptive training prescriptions (ATPs) must be developed to balance the benefits of exercise with the NMD state of the patient

The Problem •There are no current standardized clinically accepted ATPs for; • Amyotrophic lateral sclerosis – ALS • Charcot-Marie-Tooth disease – CMT • Multiple sclerosis – MS • Myasthenia gravis – MG • Duchenne’s muscular dystrophy - DMD

•Therefore patients, families, and healthcare providers are left to develops ATPs on their own

Our Hypothesis Our hypothesis has three, simple parts;

•NMDs reduce tolerance to aerobic and anaerobic exercise

•ATPs can be developed to promote exercise as allowed by the disease process

•ATPs will preset no burden for the patient beyond reason for the disease process

Key Terms •Neuromuscular disease • A disease that affects neuron signaling to or from the muscle, the neuromuscular junction,

the muscle tissue itself, or any combination of the previous factors

•Training prescription • A training protocol specifically designed by a healthcare provider for a specific patient for a

specific goal

•Adaptive training prescription • A training protocol specifically designed by a healthcare provider to match a specific physical

and/or cognitive inability of the patient

•Non-Pharmacologic therapy • An action, often but not always an exercise, prescribed by a healthcare provider for the

purpose of producing a specific outcome related to the disease state of the patient

Aerobic anti-gravity exercise in patients with Charcot- Marie-Tooth disease types 1A and X: A pilot study

KNAK, ANDERSON, & VISING – 2017

The basics CHARCOT-MARIE-TOOTH DISEASE (CMT)

•CMT is an incurable, hereditary neuropathy of the motor and sensory neurons

•Most common hereditary NMD, 1 in 2500 humans have it

•Starts as loss of sensation in periphery, soon progresses to painful muscle spasms

•Resting muscle soreness becomes common, walking can become borderline impossible

ANTI-GRAVITY EXERCISES

•Somewhat a misnomer, there are no true “anti -” gravity exercises

•Refers instead to land-based activities with some form of support structure to prevent the body experiencing the full weight of their body

•Here, a harness was used

Purpose & Methods Can anti-gravity treadmill walking improve walking and stability in CMT patients?

•5 weakened CMT patients selected, could not walk more than 10m in one bout

•10 wk ADL monitoring

•Pre-test

•10 wk supervised intervention

•Post-test

Testing •6-minute walk test

•Postural stability test – Biosway Portable Balance System 950-460

•Balance test

•Fatigue scale

•General health survey – Short-Form Health Survey v.36

•Balance survey – Berg Balance Scale

•Fitness survey

Training Program On a AlterG Antigravity Treadmill M320, 3x weekly

•5 min patient-directed warmup • Walking or stretching as patient desired

•25 min walking at 70-80% pMHR • Breaks at patient direction

AlterG Antigravity Treadmill M320 The harness structure starts at the horizontal blue lines and runs down along the grey mesh to support the patient’s weight Credit: AlterG Incorporated

Key Findings •No severe adverse effects reported

•Balance and postural stability significantly increased

•Patients reported being able to exercise (with the reduced apparent gravity) on days they otherwise could not have

Reduced gravity exercise allows greater mobility than normal conditions

Aerobic anti-gravity exercise increased balance and postural stability in CMT patients, two major areas of deficit that can result in increased morbidity and mortality

Summary & Conclusion •In no study were severe adverse effects to exercise reported

•All studies found ATPs that were well tolerated by NMD patients

•No study found evidence that any benefit of exercise was absent in NMDs

Thus;

NMDs do reduce tolerance to exercise

ATPs can be made that balance the need for exercise with the NMD process

ATPs do not present any undue burdens, and adverse effects are exceptionally rare

References Alemdaroğlu, I., Karaduman, A., Yilmaz, Ö. T., & Topaloğlu, H. (2015). Different types of upper extremity exercise training in Duchenne muscular dystrophy: Effects on

functional performance, strength, endurance, and ambulation. Muscle & Nerve, 51(5), 697-705. https://doi.org/10.1002/mus.24451 Brinkmann, J. R., & Ringel, S. P. (1991). Effectiveness of exercise in progressive neuromuscular disease. Journal of Neural Rehabilitation, 5(4), 195-199.

https://journals.sagepub.com/doi/pdf/10.1177/136140969100500401 Carter, G. T. (1997). Rehabilitation management in neuromuscular disease. Journal of Neural Rehabilitation, 11(2), 69-80.

https://journals.sagepub.com/doi/pdf/10.1177/154596839701100201 Clawson, L. L., Cudkowicz, M., Krivickas, L., Brooks, B. R., Sanjak, M., Allred, P., Atassi, N., Swartz, A., Steinhorn, G., Uchil, A., Riley, K. M., Yu, H., Schoenfeld, D. A., &

Maragakis, N. J. (2017). A randomized controlled trial of resistance and endurance exercise in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 19(3-4), 250-258. https://doi.org/10.1080/21678421.2017.1404108

Cup, E. H., Pieterse, A. J., Ten Broek-Pastoor, J. M., Munneke, M., Van Engelen, B. G., Hendricks, H. T., Van Der Wilt, G. J., & Oostendorp, R. A. (2007). Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: A systematic review. Archives of Physical Medicine and Rehabilitation, 88. https://doi.org/10.1016/j.apmr.2007.07.024

DeBolt, L. S., & McCubbin, J. A. (2004). The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis. Archives of Physical Medicine and Rehabilitation, 85(2), 290-297. https://doi.org/10.1016/j.apmr.2003.06.003

Hillman, C. H., Erickson, K. I., & Kramer, A. F. (2008). Be smart, exercise your heart: Exercise effects on brain and cognition. Nature Reviews Neuroscience, 9(1), 58-65. https://doi.org/10.1038/nrn2298

Knak, K. L., Andersen, L. K., & Vissing, J. (2017). Aerobic anti-gravity exercise in patients with Charcot-Marie-Tooth disease types 1A and X: A pilot study. Brain and Behavior, 7(12), e00794. https://doi.org/10.1002/brb3.794

Mead, G. E., Morley, W., Campbell, P., Greig, C. A., McMurdo, M. E., & Lawlor, D. A. (2010). Exercise for depression. Mental Health and Physical Activity, 2(2), 95-96. https://doi.org/10.1016/j.mhpa.2009.06.001

Pescatello, L. S., Franklin, B. A., Fagard, R., Farquhar, W. B., Kelley, G. A., & Ray, C. A. (2004). Exercise and hypertension. Medicine & Science in Sports & Exercise, 36(3), 533-553. https://doi.org/10.1249/01.mss.0000115224.88514.3a Rahbek, M. A., Mikkelsen, E. E., Overgaard, K., Vinge, L., Andersen, H., & Dalgas, U. (2017). Exercise in myasthenia gravis: A feasibility study of aerobic and resistance

training. Muscle & Nerve, 56(4), 700-709. https://doi.org/10.1002/mus.25552 Shaw, K. A., Gennat, H. C., O'Rourke, P., & Del Mar, C. (2006). Exercise for overweight or obesity. Cochrane Systematic Review - Intervention, (4).

https://doi.org/10.1002/14651858.CD003817.pub3 Westerberg, E., Molin, C. J., Lindblad, I., Emtner, M., & Punga, A. R. (2017). Physical exercise in myasthenia gravis is safe and improves neuromuscular parameters and

physical performance-based measures: A pilot study. Muscle & Nerve, 56(2), 207-214. https://doi.org/10.1002/mus.25493

Thanks for a great semester, Britton, and take care.

https://doi.org/10.1002/mus.24451

https://journals.sagepub.com/doi/pdf/10.1177/136140969100500401

https://journals.sagepub.com/doi/pdf/10.1177/154596839701100201

https://doi.org/10.1080/21678421.2017.1404108

https://doi.org/10.1016/j.apmr.2007.07.024

https://doi.org/10.1016/j.apmr.2003.06.003

https://doi.org/10.1038/nrn2298

https://doi.org/10.1002/brb3.794

https://doi.org/10.1016/j.mhpa.2009.06.001

https://doi.org/10.1249/01.mss.0000115224.88514.3a

https://doi.org/10.1002/mus.25552

https://doi.org/10.1002/14651858.CD003817.pub3

https://doi.org/10.1002/mus.25493