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Diabetic Peripheral Neuropathy

Patient examination guidelines for practitioners

Part 1 – 1. Background of diabetic peripheral neuropathy. 2.History and physical exam


Diabetic neuropathy is the most common complication of both type 1 (T2DM) and type 2 (T2DM) diabetes.  Diabetes causes a number of different neuropathic complication to include sympathetic and parasympathetic autonomic dysfunction .  This blog post focuses on the causes of diabetic peripheral neuropathy (DPN) and clinical exam of patients with DPN.  This post is intended to act as a guideline for lower extremity health practitioners including podiatrists, primary care physicians, NP’s and PA’s.  The objective of this post is to create a framework for a meaningful patient exam of patients with diabetic peripheral neuropathy.

Background of diabetic peripheral neuropathy


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 subsequent 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)

Annual cost per diabetic patient                                                         $6,632

Annual cost per diabetic patient with DPN                                           $12,492

Annual cost per diabetic patient with painful neuropathy                      $30,755

The physiopathology 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 at 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)



Lifetime incidence of DPN



Potential change of DPN with treatment



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 Polyol 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.

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 their sleep cycle

Tinel’s sign of posterior tibial nerve, deep peroneal nerve and common peroneal nerve 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 inability to feel the floor.

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

Clinical Exam of Patients with Diabetic Peripheral neuropathy


  • When were you first diagnosed with diabetes?
  • Have you used Metformin?  And if so how long?
  • Have you been insulin dependent?  And if so how long?
  • What is your current HbA1c?
  • Are you familiar with your A1c history and what the A1c test is?
  • Upon initiation of treatment, how rapidly did your A1c change?
  • Do you feel that you have lost sensation in your feet?
  • Do you experience tingling in your feet?
  • If you do experience tingling in your feet, does it keep you awake at night?

Physical exam of patients with diabetic peripheral neuropathy

  • Vascular exam
  • DP and PT pulses
  • Capillary refill time
  • Skin exam
  • Skin turgor, hair growth, areas of callus, wounds, overall hygiene
  • Neurological exam
  • Light touch (Weinstein monofilament), Tinel’s sign of the tarsal canal, deep peroneal nerve and common peroneal nerve, deep reflexes, vibratory sensation

Orthopedic exam

  • Muscle strength testing, documentation of foot structure

Labs and related testing

  • Fasting serum blood glucose, hemoglobin A1c, Vitamin B12 level
  • Small fiber nerve density testing when indicated
  • Electrodiagnostic (NCV/EMG) studies are not indicated

Clinical caveats


  • There is no direct correlation between type of duration of diabetes and onset of LOPS.
  • There is prevalence of LOPS in type 1 vs. type 2 diabetes


  • When were you first diagnosed with diabetes?  Although there is not a direct correlation between the onset of and severity of DPN, this question provides an opportunity for the patient to describe their history, treatment and compliance.
  • Have you used Metformin?  Metformin can deplete vitamin B12 that can contribute to DPN.
  • Have you used insulin and if so, for how long?  Insulin use can often define the severity of hyperglycemia.  Although not a direct correlation, the more difficult hyperglycemia is to manage, the greater the potential for DPN.
  • What is your current A1c?  Optimal treatment of diabetes is a dance between provider and patient.  The more informed the patient is regarding their A1c, the greater the compliance.
  • Are you familiar with your A1c history and what the A1c test is?  If treatment of DM and DPN is a dance, here is your first opportunity to educate your partner.  Your partner should know each step of the dance and why the steps are important.
  • Upon initiation of treatment, how rapidly did your A1c change?  Are the symptoms of DPN due to TIND?
  • Do you feel that you have lost sensation in your feet?  What stage is the patient in their DPN?  This question provides an opportunity to discuss the importance of LOPS.  Showing a patient that they cannot feel light touch with a Weinstein monofilament helps to define LOPS for the patient.
  • Do you experience tingling in your feet and if so, does it keep you awake at night?  Is treatment of the DPN necessary?
  • Symptoms
  • DPN symptoms are most significant when trying to fall asleep.  When active by day, the mind is preoccupied with tasks at hand.  When trying to fall asleep, significant symptoms of DPN will limit a patient’s ability to fall asleep or maintain a deep sleep cycle.


  • Serial hemoglobin A1c levels should be used to monitor the rate of change and decrease of A1c during treatment.
  • Depleted B12 is often a symptom of chronic Metformin use.

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  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.
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Dr. Jeffrey Oster
Jeffrey A. Oster, DPM

Medical Director

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