# Exercise as it relates to Disease/Effects of long term aerobic exercise on the development of neuropathy in Diabetic individuals
## Topic Article

Balducci, S., Iacobellis, G., Parisi, L., Di Biase, N., Calandriello, E., Leonetti, F., & Fallucca, F. (2006). Exercise Training can modify the Natural History of Diabetic Peripheral Neuropathy. Journal Of Diabetes And Its Complications, 20(4), 216-223. http://dx.doi.org/10.1016/j.jdiacomp.2005.07.005

## What is the background to this research?

Diabetic Peripheral Neuropathy (DPN) is a common complication in diabetic populations that results in a type of nerve damage involving axon loss and segmental demyelination within nerves $^{1,2}$. The main cause of DPN is Hyperglycaemia, otherwise know as prolonged high blood sugar. High blood sugar can damage nerve fibres and hence interfere with the ability of nerves to transmit signals throughout the body, whilst also weakening vessel wall structures therefore reducing the supply of nutrients and oxygen to nerves $^3$. DPN ultimately reduces quality of life as it reduces sensation in the limbs, chronic pain, joint deterioration, ulcers and in severe cases loss of limbs $^{1,2,4}$. Researchers believe physical activity may be the key to preventing, or reducing the prevalence of DPN as exercise aids insulin sensitivity whilst other exercise induced vascular and metabolic changes have benefits for nerve perfusion and function $^{1,5}$. A study by Balducci has shown that aerobic exercise does have benefits in preventing the onset of DPN as well as positive effects on nerve conduction and vibration threshold in diabetic individuals.

## Where is the research from?

The study was conducted by researchers from the Metabolic Fitness Association, Monterotondo, Rome; Department of Clinical Sciences, Endocrinology, University of Rome; Department of Clinical Neurology, La Sapienza University, Rome; Department of Clinical Sciences, La Sapienza University, Rome; Center for Human Nutrition, The University of Texas Southwestern Medical Center at Dallas and the Pietro Hospital, Rome, Italy. The completed study was published in the Journal of Diabetes and its Complications.

## What kind of research was this?

Balducci's study was a 4-year prospective randomized intervention study, conducted in accordance with the Declaration of Helsinki guidelines. The intervention comprised of physical activity of 4hr/ week under supervision of a metabolic fitness assistant who supervised technical aspects of the proposed exercise. This study, being a randomised control trial, is considered a level two research intervention by the National health and Medical Research Council $^6$. This is the best method of performing this study and shows that the results presented by Balducci give strong evidence that aerobic exercise has a positive effect on DPN prevention and reduction.

## What did the research involve?

Balducci's study involved 78 participants, all of which showed no signs and symptoms of DPN. This group was divided into a control group of 47 and exercise group of 31, who participated in 4hr/ week supervised brisk walking on a treadmill between 50-85% heart rate reserve. Researchers monitored exercise expenditure through heart rate monitors each session whilst also documenting changes in vibration perception threshold, nerve distal latency, nerve conduction velocity and nerve action potential amplitude in the lower limbs on a yearly basis. Through monitoring of nerves in the lower limb, researchers where able to see changes in peripheral nerves and how such changes coincided with exercise participation vs no exercise. Participation and compliance was on average 90% over the four year study so outcomes can be considered reliable.

## What were the basic results?

The results of Balducci's study showed two main findings:
* The development of both sensory and motor DPN was much higher in the control group than exercise group. Sensory showed a 29.8% development in Control group vs 6.45% development in the Exercise group, whilst Motor showed a 17% development in Control group vs 0% development in the Exercise group.
* There were significant changes in peripheral nerves. Conduction Velocity of peroneal motor nerve significantly increased in exercise group whilst sural sensory nerve significantly decreased in the control. Vibration Perception Threshold increased significantly in those from the control group.

## What conclusions should be taken away from this research?

Balducci's has concluded that long term aerobic exercise can prevent the onset of DPN and also modify the natural history of both motor and sensory neuromuscular parameters. The study was the first long term exercise intervention, so they believe that this is the reason for seeing significant benefits of exercise on diabetics $^1$. Use of supervision during the study also influenced high compliance rates and hence resulted in more accurate findings from this study. Researchers believe the benefit of exercise on DPN is its effect on insulin. Insulin is the only mechanism the body has to lower blood glucose (sugar) levels. When exercising, glucose requirement in the cell increases. This triggers the release of insulin, which binds to glucose molecules and promotes its delivery into working muscle cells. All together, this increases insulin sensitivity and removes excess glucose from the blood, hence lowering the chance of prolonged hyperglycaemic states, ultimately preventing nerve damage $^{7,8}$. Balducci recommend that submaximal, easily reproducible and reliable exercise, of 4hr/ week, is needed to see positive effects on DPN. This exercise prescription is mirrored through Diabetes Australia's guidelines of moderate intensity exercise performed at a minimum of 30 minutes of planned exercise a day $^5$. Balducci recognise that the limitation of the study was that it needs to be performed on a larger population.

## What are the implications and practical advice of this research?

Balducci's research has provided evidence that shows long term aerobic exercise can reduce the onset of DPN and also modify the natural history of the disease $^1$. Exercise of this type has been shown to have a beneficial effect on insulin which in turn reduces prolonged hyperglycaemic states $^{7,8}$. This information has a high impact on the diabetic population as they now have a means of potentially preventing the onset of such a life changing and debilitating disease. Balducci's exercise intervention, if replicated similarly and with high compliance rates, could significantly improve the health of diabetics. The study also paves the way for further research in this area, potentially of different durations and with different exercise prescription.

## Further information and resources
#### Diabetes Australia

https://www.diabetesaustralia.com.au Helpline: 1300 136 588

#### Support Groups

* Type 1 Diabetes Support Groups: http://www.jdrf.org.au/type-1-diabetes/support-groups
* NSW Diabetes Support Groups: https://diabetesnsw.com.au/support-diabetes-nsw/support-group-network/
* Queensland Diabetes Support Groups: http://www.diabetesqld.org.au/find-support/support-groups.aspx
* Victoria Support Groups: https://www.diabetesvic.org.au/support-groups

#### Diabetic Neuropathy Information

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/diabetic-neuropathy

## References

* Balducci, S., Iacobellis, G., Parisi, L., Di Biase, N., Calandriello, E., Leonetti, F., & Fallucca, F. (2006). Exercise Training can modify the Natural History of Diabetic Peripheral Neuropathy. Journal Of Diabetes And Its Complications, 20(4), 216-223. http://dx.doi.org/10.1016/j.jdiacomp.2005.07.005
* Mayoclinic.org,. (2015). Diabetic neuropathy - Mayo Clinic. Retrieved 12 September 2015, from http://www.mayoclinic.org/diseases-conditions/diabetic-neuropathy/basics/definition/con-20033336
* Medscape,. (2015). Diabetic Neuropathy: An Intensive Review. Retrieved 13 September 2015, from http://www.medscape.com/viewarticle/467524_2
* Galer, B., Gianas, A., & Jensen, M. (2000). Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Research And Clinical Practice, 47(2), 123-128. doi:10.1016/s0168-8227(99)00112-6
* Exercise. (2016). Diabetesaustralia.com.au. Retrieved 27 September 2016, from https://www.diabetesaustralia.com.au/exercise
* Merlin, T., Weston, A., & Tooher, R. (2016). NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. National Health and Research Council. Retrieved 24 September 2016, from https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf
* Douen, A., Ramlal, T., Rastogi, S., Bilan, P., Cartee, G., & Vranic, M. et al. (1990). Exercise Induces Recruitment of the “Insulin-responsive Glucose Transporter”. Journal Of Biological Chemistry, 265(23), 13427-13430. Retrieved from http://www.jbc.org/content/265/23/13427.full.pdf
* O’Gorman, D., Karlsson, H., McQuaid, S., Yousif, O., Rahman, Y., & Gasparro, D. et al. (2006). Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes. Diabetologia, 49(12), 2983-2992. http://dx.doi.org/10.1007/s00125-006-0457-3