Diabetic Peripheral Neuropathy

One emerging treatment category for patients with diabetes is exercise physiology. As we reported recently, an important study finds that weightbearing activity for patients with diabetic peripheral neuropathy (DPN) does not increase the rate of foot ulcers.4 Moreover, the usual patterns of decline associated with DPN can be transformed into patterns of improvement.

Patients with diabetic peripheral neuropathy who engage in exercise therapy regularly realise improvements in nerve conduction velocity,5 pain interference,6 general fatigue,7 balance,8 gait,9 and mobility.10 In animal models, exercise in DPN leads to decreased pain,11 normalised epidermal innervation,12 enhanced nerve regeneration,13 and restored electrophysiological function.14

One of the less discussed effects of diabetes is limited joint mobility syndrome (LJMS).15 In fact, LJMS presents as the most common musculoskeletal complication in diabetes. It involves stiffness in the joints of the ankle and big toe. More importantly, LJMS results in alterations to peak plantar pressures (PPP) that, in turn, add to the incidence of diabetic foot ulcerations. Theoretically, a DPN exercise therapy intervention should include activities designed to restore ankle and toe range of motion (ROM), thereby normalising PPP, and lowering the risk of diabetic foot ulceration. However, the literature evaluating such interventions has produced mixed results. 

To see if more clarity can be established, researchers from the U.K.’s University of Plymouth recently completed a systematic review and meta-analysis.16 The science on the best exercise therapy interventions for LJMS is still emerging. Some interventions tested were reported to be ineffective. For instance, stretching alone in eight-minute sessions produced no results. Nevertheless, the meta-analyses find that exercise therapy for diabetes-related LJMS creates statistically significant improvements in PPP and ankle and hallux range of motion. Effective treatment plans tend to involve warmup, stretching, strengthening, and mobilisation, in longer sessions occurring multiple times per week. Interestingly, the difference in ankle ROM between patients who developed foot ulcers and those who did not was quite small (2° to 4°). 

Much research is needed to establish the optimal exercise therapy protocol for minimising foot ulceration in DPN. Nevertheless, the current study is encouraging for including LJMS interventions in overall exercise physiology programs for patients with DPN. To ensure safety, exercise programs closely supervised by an exercise physiologist will include ongoing screening for integumentary, nervous, musculoskeletal, vascular, endocrine, and cardiovascular systems. Footwear will also be evaluated before each exercise session, and patients will be thoroughly trained in all these aspects of safe exercise. Exercise physiology can implement multi-focused, supervised exercise plans designed to achieve aerobic, gait, balance, and strength benefits, while triggering the non-metabolic mechanisms associated with nerve improvement. The treatment plans will give people with DPN the confidence and motivation they need to improve activity levels long-term, empowering them to have greater control over their disease and to reverse the common patterns of decline.

References

1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Research and Clinical Practice. 2019 Nov 1;157:107843.

2. Kerr M, Barron E, Chadwick P, Evans T, Kong WM, Rayman G, Sutton‐Smith M, Todd G, Young B, Jeffcoate WJ. The cost of diabetic foot ulcers and amputations to the National Health Service in England. Diabetic Medicine. 2019 Aug;36(8):995-1002.

3. AIHW. Health Expenditure Australia 2017–18.

4. LeMaster JW, Mueller MJ, Reiber GE, Mehr DR, Madsen RW, Conn VS. Effect of weight-bearing activity on foot ulcer incidence in people with diabetic peripheral neuropathy: feet first randomized controlled trial. Physical Therapy. 2008 Nov 1;88(11):1385-98.

5. Dixit S, Maiya AG, Shastry BA. Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: a single blind, parallel group randomized controlled trial. Journal of Diabetes and its Complications. 2014 May 1;28(3):332-9.

6. Yoo M, D'Silva LJ, Martin K, Sharma NK, Pasnoor M, LeMaster JW, Kluding PM. Pilot study of exercise therapy on painful diabetic peripheral neuropathy. Pain Medicine. 2015 Aug 1;16(8):1482-9.

7. Fisher MA, Langbein WE, Collins EG, Williams K, Corzine L. Physiological improvement with moderate exercise in type II diabetic neuropathy. Electromyography and Clinical Neurophysiology. 2007 Jan 1;47 (1):23-8.

8. Akbari M, Jafari H, Moshashaee A, Forugh B. Do diabetic neuropathy patients benefit from balance training?. Journal of Rehabilitation Research & Development. 2012 Mar 1;49(2).

9. Allet L, Armand S, De Bie RA, Golay A, Monnin D, Aminian K, Staal JB, de Bruin ED. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010 Mar;53:458-66.

10. Kruse RL, LeMaster JW, Madsen RW. Fall and balance outcomes after an intervention to promote leg strength, balance, and walking in people with diabetic peripheral neuropathy:“feet first” randomized controlled trial. Physical Therapy. 2010 Nov 1;90(11):1568-79.

11. Chen YW, Hsieh PL, Chen YC, Hung CH, Cheng JT. Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats. Anesthesia & Analgesia. 2013 Feb 1;116(2):482-90.

12. Groover AL, Ryals JM, Guilford BL, Wilson NM, Christianson JA, Wright DE. Exercise-mediated improvements in painful neuropathy associated with prediabetes in mice. Pain®. 2013 Dec 1;154(12):2658-67.

13. Malysz T, Ilha J, do Nascimento PS, De Angelis K, Schaan BD, Achaval M. Beneficial effects of treadmill training in experimental diabetic nerve regeneration. Clinics. 2010 Jan 1;65(12):1329-37.

14. Li H, Shen Z, Lu Y, Lin F, Wu Y, Jiang Z. Muscle NT-3 levels increased by exercise training contribute to the improvement in caudal nerve conduction velocity in diabetic rats. Molecular Medicine Reports. 2012 Jul 1;6(1):69-74.

15. Francia P, Anichini R, Seghieri G, De Bellis A, Gulisano M. History, prevalence and assessment of limited joint mobility, from stiff hand syndrome to diabetic foot ulcer prevention: a narrative review of the literature. Current Diabetes Reviews. 2018 Oct 1;14(5):411-26.

16. Lepesis V, Marsden J, Rickard A, Latour JM, Paton J. Systematic review and meta‐analysis of the effects of foot and ankle physical therapy, including mobilisations and exercises, in people with diabetic peripheral neuropathy on range of motion, peak plantar pressures and balance. Diabetes/Metabolism Research and Reviews. 2023 Jul 10:e3692.