Diabetic Peripheral Neuropathy - patient examination guidelines for practitioners (part 1)

Part 1 – Background of diabetic peripheral neuropathy

Objectives

Diabetic peripheral neuropathy is the most common complication of both type 1 (T1DM) and type 2 (T2DM) diabetes.  Diabetes causes a number of different neuropathic complications to include sympathetic and parasympathetic autonomic dysfunction.  Part 1 of this three-part blog post focuses on the causes of diabetic peripheral neuropathy (DPN), the economic impact of DPN and proposes a staging classification for clinicians who treat patients with DPN. This post is intended to act as a guideline for lower extremity health practitioners including podiatrists, primary care physicians, NPs and PAs.  The objective of this post is to create a framework for a meaningful patient exam of patients with diabetic peripheral neuropathy.

Click this link to print patient guidelines for diabetic foot care.
Click this link to print patient guidelines for treatment of diabetic peripheral neuropathy.

Background of diabetic peripheral neuropathy

Introduction

The incidence of diabetes makes it one of the most significant health issues of the 21st century.  Current estimates note that 10% of the general population has diabetes with a global incidence to reach 366 million people by 2020. (1)  Diabetic peripheral neuropathy (also called distal symmetrical polyneuropathy) is the most common complication of diabetes and is found in 90% of type 1 and type 2 diabetics. (2-6) 

The term neuropathy is a paradox in that it describes both loss of sensation and increased sensation (hyperalgesia).  Loss of protective sensation (LOPS) leads to significant foot wounds that may result in loss of limb.  Loss of sensation also leads to gait instability and falls.  30% of all cases of DPN will have painful neuropathy. (5-8)  The annual cost of treating diabetes increases with DPN, LOPS and even more significantly with the onset of painful neuropathic neuropathy.  It has been estimated that 27% of the cost of treating diabetes is associated with the treatment of DPN. (9-11)                                              

The pathophysiology of diabetic neuropathy

Although the precise cause of diabetic peripheral neuropathy is not fully understood, there are several key factors that are attributed to the onset of peripheral nerve pain in patients with sustained diabetes.(12)  Those theories include –

• Polyal pathway hyperactivity
• Oxidative and nitrosative stress
• Microvascular changes
• Channels sprouting
• Microglial activation
• Central sensitization
• Brain plasticity

Is DPN exclusively due to sustained hyperglycemia?  Recent research has begun to look at metabolic syndrome as a complimentary condition that may influence the onset and severity of DPN.  Conditions considered a part of metabolic syndrome that may affect the onset and treatment of DPN include obesity, hypertriglyceridemia, hypercholesterolemia, hypertension and cigarette smoking.(13,14)  The concept that these commorbidities are in part a cause for DPN is support by the fact that the DPN symptoms of T1DM are more responsive to treatment than the DPN symptoms of T2DM.(15-20)

Therefore, in addition to hyperglycemia, a host of other factors need to be considered when assessing the root cause of damage to the peripheral nerve.  Additional influencing factors include toxic adiposity, oxidative stress, mitochondrial dysfunction, activation of the polyal pathway, accumulation of advanced glycation end products (AGE’s) and elevated inflammatory markers. (2,21)

Treatment-induced neuropathy in diabetes (TIND)

TIND is described as “acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large improvement in glycemic control specified as a decrease in glycosylated HbA1c of more than 2% points over 3 months”. (22)  TIND was first described by Caravati in 1933 and originally called insulin neuritis. (22)  The underlying pathophysiology of TIND is poorly understood, but TIND is thought to be secondary to rapid change in Hbg A1c that results in arterio-venous changes within the nerve fiber resulting in hypoxemia of the nerve.(23,24)  Compared to non-TIND DPN, symptoms of TIND are found to be more severe and less responsive to opioids.  TIND is self-limiting and resolves over a period of 6-12 months as HbA1c levels normalize.  At the onset of treatment of diabetes, the risk of developing TIND is greater than 10%.(25)

Staging of diabetic peripheral neuropathy symptoms

The following is a staging schema that I use in my clinic to define the symptoms of diabetic peripheral neuropathy and the indications for treatment.

Stage 1

Symmetrical loss of sensation in the toes and forefoot as measured by Weinstein monofilament but not known to the patient at the time of exam.

No symptoms of pins and needles.

Tinel’s sign of posterior tibial nerve, deep peroneal nerve and common peroneal nerve negative.

Stage 2

Symmetrical loss of sensation in the toes and forefoot as measured by Weinstein monofilament known to the patient at the time of exam.

Symptoms of pins and needles that do not affect the patient's sleep cycle.

Tinel’s sign of posterior tibial nerve, deep peroneal nerve and common peroneal nerve positive or negative.

Stage 3

Symmetrical loss of sensation in the toes and forefoot as measured by Weinstein monofilament known to the patient at the time of exam.

Symptoms of pins and needles that negatively affect the patient’s sleep cycle.

Tinel’s sign of posterior tibial nerve, deep peroneal nerve and common peroneal nerve positive.

Stage 3 – late-stage

Additional symptoms may include –

Loss of sensation that progresses to both hands and feet in a stocking and glove distribution.

Instability of gait secondary to loss of proprioception and the inability to feel the floor.

Motor changes to include foot drop, steppage gait, and interosseous muscle wasting. 

Summary

Diabetic peripheral neuropathy is the most common complication of type 1 and type 2 diabetes.  The social and economic impact of diabetic peripheral neuropathy is significant.  An understanding of the underlying pathophysiology and staging of the neuropathy can help to treat these challenging patients. 

In part 2 of this three-part blog post, we'll take a close look at the history and physical exam of the patient with diabetic peripheral neuropathy.  In part 3, we'll drill down into treatment options of the patient with diabetic peripheral neuropathy.

Click this link to print patient guidelines for diabetic foot care.
Click this link to print patient guidelines for treatment of diabetic peripheral neuropathy.

1. Hossain P, Kawar B, El Nahas M: Obesity and diabetes in the developing world--a growing challenge. N Engl J Med. 2007;356(3):213–5. 10.1056/NEJMp068177 [CrossRef]
2. Singh R, Kishore L, Kaur N: Diabetic peripheral neuropathy: current perspective and future directions.Pharmacol Res. 2014;80:21–35. 10.1016/j.phrs.2013.12.005 [CrossRef] 
3. Boulton AJ: Management of Diabetic Peripheral Neuropathy. Clin Diabetes. 2005;23(1):9–15. 10.2337/diaclin.23.1.9 [CrossRef]
4. Tesfaye S, Selvarajah D: Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012;28(Suppl 1):8–14. 10.1002/dmrr.2239 [CrossRef]
5. Tesfaye S, Vileikyte L, Rayman G, et al. : Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27(7):629–38. 10.1002/dmrr.1225[CrossRef]
6. Tesfaye S, Boulton AJ, Dyck PJ, et al. : Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285–93. 10.2337/dc10-1303[PMC free article] [CrossRef]
7. Quattrini C, Tesfaye S: Understanding the impact of painful diabetic neuropathy. Diabetes Metab Res Rev. 2003;19(Suppl 1):S2–8. 10.1002/dmrr.360 [CrossRef]
8. Callaghan BC, Cheng HT, Stables CL, et al. : Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521–34. 10.1016/S1474-4422(12)70065-0 [PMC free article][CrossRef]
9. Sadosky A, Mardekian J, Parsons B, et al. : Healthcare utilization and costs in diabetes relative to the clinical spectrum of painful diabetic peripheral neuropathy. J Diabetes Complications. 2015;29(2):212–7. 10.1016/j.jdiacomp.2014.10.013[CrossRef] 
10.  American Diabetes Association: Economic costs of diabetes in the U.S. in 2012. Diabetes Care.2013;36(4):1033–46. 10.2337/dc12-2625 [PMC free article] [CrossRef] 
11. Gordois A, Scuffham P, Shearer A, et al. : The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003;26(6):1790–5. 10.2337/diacare.26.6.1790[CrossRef]
12. Schreiber AK, Nones C, Reis RC, Chichorro JG, Cunha JM: Diabetic neuropathic pain: Physiopathology and treatment. World J Diabetes. 2015 Apr 15; 6(3): 432–444.
13. Callaghan B, Feldman E: The metabolic syndrome and neuropathy: therapeutic challenges and opportunities. Ann Neurol. 2013;74(3):397–403. 10.1002/ana.23986 [PMC free article] [CrossRef] 
14. Zilliox L, Russell JW: Treatment of diabetic sensory polyneuropathy. Curr Treat Options Neurol.2011;13(2):143–59. 10.1007/s11940-011-0113-1 [PMC free article] [CrossRef]
15. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329(14):977–86. 10.1056/NEJM199309303291401[CrossRef]
16. Linn T, Ortac K, Laube H, et al. : Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients. Metabolism. 1996;45(12):1508–13. 10.1016/S0026-0495(96)90180-8] [CrossRef]
17. Duckworth W, Abraira C, Moritz T, et al. : Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129–39. 10.1056/NEJMoa0808431[CrossRef]
18. Ismail-Beigi F, Craven T, Banerji MA, et al. : Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet.2010;376(9739):419–30. 10.1016/S0140-6736(10)60576-4 [PMC free article] [CrossRef] 
19. Gibbons CH, Freeman R: Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy. Ann Neurol. 2010;67(4):534–41. 10.1002/ana.21952 [PMC free article] [CrossRef]
20. Tesfaye S, Malik R, Harris N, et al. : Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis). Diabetologia. 1996;39(3):329–35. 10.1007/s001250050449[CrossRef]
21. Tesfaye S, Chaturvedi N, Eaton SE, et al. : Vascular risk factors and diabetic neuropathy. N Engl J Med.2005;352(4):341–50. 10.1056/NEJMoa032782[CrossRef]
22. Caravati CM.  Insulin Neuritis: a case report. VA. Med.Monthly. 1933;59:745-746.
23. Tran C, Philippe J, Ochsner F, et al. : Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy. Swiss Med Wkly. 2015;145:w14131. 10.4414/smw.2015.14131[CrossRef] 
24. Callaghan BC: The Impact of the Metabolic Syndrome on Neuropathy. Reference Source
25. Callaghan B, Feldman E: The metabolic syndrome and neuropathy: therapeutic challenges and opportunities. Ann Neurol. 2013;74(3):397–403. 10.1002/ana.23986 [PMC free article]  [CrossRef]

Jeff

Jeffrey A. Oster, DPM

Medical Advisor
Myfootshop.com

Updated 12/24/2019

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