Although the symptoms of DN greatly vary depending on types and location of affected sensory fibers, the most commonly reported symptoms include pain and dysesthesia (unpleasant sensations of burning, tingling or numbness). Pain intensity may vary, and can be described as burning, sticking, lancinating, prickling, aching, boring and/or excessively sensitive. Pain occurs initially at the most distal portions of the longest affected nerves, typically affecting fingers and toes, before proceeding proximal, sometimes with a "stocking-glove" pattern of loss of sensory function and pain. Loss of sensory function especially in nociceptive fibers, with or without accompanying pain and/or dysesthesia can lead to painless injuries and subsequent complications.

Pain-mediated sleep disturbances are common, with higher intensities of pain experienced during the night, potential feelings of tightness around the extremities, and/or electrical tingling sensations. Later or less common symptoms include weakness, mononeuropathies (such as carpal tunnel syndrome or footdrop), truncal radiculoneuropathy (pain over lower thoracic or abdominal wall), diabetic amyotrophy (associated with intense muscular pain and weakness, and proximal thigh muscle wasting) and in very rare cases cranial neuropathies.

Examination of the patient history may provide further indications of risk factors for the development of DN, such as prolonged duration of DM (over 10 years), older age (70 years or over), increased body height, and chronic or poorly controlled hyperglycemia [4] [10]. Additional contributing factors present in the history may include dyslipidemia with increased triglycerides and hypertension, as well as recent falls due to impaired balance or gait [11].

• Falling

  FINDINGS: Impairments in lower limb muscles reduce functional capacity and contribute to altered gait, increased fall risk, and impaired balance in patients with DPN. [ncbi.nlm.nih.gov]

  Injuries from falls are widely known to be a leading cause of hospitalization and mortality in the elderly. 8 [mdedge.com]

  Abstracts often contained words such as “falls risk” and “fear of falling” in addition to balance. [journals.lww.com]

• Limb Pain

  Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. [ncbi.nlm.nih.gov]

  Electrical spinal cord stimulation has been used to treat several chronic painful conditions, including phantom limb pain, vascular disease, and severe neuropathy. [clinical.diabetesjournals.org]

• Feet and Hand Pain

  In feet or hands: Pain Numbness Tingling Sensations EVALUATION AND TESTS (Not all evaluation and tests may be necessary.) [peripheralneuropathycenter.uchicago.edu]

• Chronic Infection

  This finding is an important concern for patients with DPN because their falls are likely to be injurious and lead to bone fractures, poorly healing wounds, and chronic infections that may require amputation. [ncbi.nlm.nih.gov]

• Animal Bite

  All animal bites have the potential to cause significant infection. In the UK, dogs are the most common source of bites. Incidence of hospital attendances attributable to dog bites has risen over the last decade. [ncbi.nlm.nih.gov]

• Numbness of the Feet

  Burning, tingling, numbness to your feet?! Does this sound familiar? Are you a diabetic? If you are, and are experiencing some or all of the symptoms, you are experiencing classic signs of diabetic peripheral neuropathy. [faant.com]

  Numbness in the feet can also contribute to loss of balance. Your foot may begin to look deformed. This is the result of unusual shifts in weight caused by walking abnormally and the loss of nerve function, which can affect the muscles. [healthline.com]

  Your provider will also check for numbness in your feet by touching your foot with a monofilament. It looks like a stiff piece of nylon fishing line or a bristle in a hairbrush. Other ways to check your nerves include using a tuning fork. [blackdoctor.org]

  Symptoms can range from pain and numbness in your feet to problems with the functions of your internal organs, such as your heart and bladder. What Is Diabetic Neuropathy? Diabetic neuropathy is nerve damage that is caused by diabetes. [niddk.nih.gov]

• Foot Pain

  A 45-year-old female complained of bilateral plantar foot pain. She had been treated for diabetes mellitus for 5 years. Oral analgesics did not resolve her pain. Even nerve block therapy did not adequately relieve her pain. [ncbi.nlm.nih.gov]

  Pain, Axsain, Capsicum Oleoresin, Capzasin, Salonpas Pain Patch with Capsaicin, Zostrix, Capsin, Capzasin-HP, Icy Hot PM Patch, Trixaicin, Capzasin-P, Menthac Arthritis Cream with Capsaicin, Salonpas Gel-Patch, Sloan's Liniment, Trixaicin HP, Capzasin [drugs.com]

  Typically, these topical medications are used by people who have foot pain (common in diabetic peripheral neuropathy). [endocrineweb.com]

  Neuropathic foot pain is one of a number of conditions affecting the feet which are termed as problems of ‘ the diabetic foot ’. For this reason, people with diabetes are advised to undergo a foot examination once each year. [diabetes.co.uk]

• Neuropathic Arthropathy

  Charcot joint is also called neuropathic arthropathy and occurs when the bones in the feet fracture or "powder" and the foot becomes misaligned. [joslin.org]

• Restless Legs Syndrome

  Some may even describe restless leg syndrome. In the patient with diabetes, first and foremost you need to make sure that there is optimum glycemic control. [podiatrytoday.com]

• Bilateral Plantar Foot Pain

  A 45-year-old female complained of bilateral plantar foot pain. She had been treated for diabetes mellitus for 5 years. Oral analgesics did not resolve her pain. Even nerve block therapy did not adequately relieve her pain. [ncbi.nlm.nih.gov]

• Peripheral Neuropathy

  RESULTS: In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3% [ncbi.nlm.nih.gov]

• Neuralgia

  OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians [ncbi.nlm.nih.gov]

  Most neuralgia sufferers feel acute pan in a specific part of the body. Sensations can range from a steady burning to a pricking or electrical shock. Diabetic Neuropathy Diabetic neuropathy is nerve damage caused by diabetes. [arizonapaintreatmentcenters.com]

  Code: E11.42 Code Name: ICD-10 Code for Type 2 diabetes mellitus with diabetic polyneuropathy Block: Diabetes mellitus (E08-E13) Details: Type 2 diabetes mellitus with diabetic polyneuropathy Type 2 diabetes mellitus with diabetic neuralgia E11 Use additional [aapc.com]

  An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy, CNS Drugs 2008; volume 22(5): pages 417-42. [passeportsante.net]

• Sleep Disturbance

  disturbances. 18 Clinical Management Management of DPN can be classified into two strategies: treating the underlying cause and targeting the relief of symptoms. [uspharmacist.com]

  Pain-mediated sleep disturbances are common, with higher intensities of pain experienced during the night, potential feelings of tightness around the extremities, and/or electrical tingling sensations. [symptoma.com]

• Absent Ankle Reflex

  The Toronto consensus criteria define probable neuropathy as the presence of two or more of the following: neuropathic symptoms, decreased distal sensation, or decreased or absent ankle reflexes. [f1000research.com]

• Cranial Nerve Involvement

  The patient with cranial nerve involvement usually has diplopia and single third, fourth, or sixth nerve weakness on examination but the pupil is spared. A full recovery of function occurs in 6-12 weeks. [health.am]

Foot exams

Regular foot exams should routinely be offered annually to people with DM, while those with DPN may need more frequent examinations. A comprehensive foot exam should include assessment of skin, muscles, bones, circulation and sensory functions. The latter are usually assessed by touching the feet with a bristled nylon monofilament or by pin pricking. A lack of response to stimulation indicates loss of protective sensation and/or feeling, and puts affected patients at risk of developing foot ulcers or painless injuries. Additional elements of the foot exam include assessment of perception of temperature, as well as vibration perception e.g. using a tuning fork.

Other tests

A bona fide diagnosis or assessment of DN or DPN might require additional tests. Studies assessing neuronal conduction by evaluating the transmission of electrical current through a nerve can be used to evaluate disease progression and the extent of neuronal damage. Electromyography measures the muscular response to electrical signals transmitted by nerves in the vicinity. Despite their prognostic value, these tools are rarely required for diagnosis of DN.

Evaluations of function and responses of internal organs represent additional diagnostic tools for DN. Alterations in heart rate variability can indicate impaired responses to deep breathing, as well as the changes in blood pressure and posture. Ultrasound examination of internal organs such as the bladder may be useful for morphological and functional assessment, such as complete emptying of the bladder after urination. Skin biopsy and intra-epidermal nerve fiber density measurements can provide further information on disease progression [12].

Stable glycemic control represents the cornerstone of management and therapy, as glycemic fluctuations have been associated with neuronal aggravation and increased intensities of pain [13]. Symptomatic treatment by using pain relievers or non-steroid anti-inflammatory drugs (NSAIDs) may be helpful, as well as self management by appropriate and pain-relieving attire (loos clothing, supportive footwear).

Tricyclic drugs can be effective for pain relief, but may not be suitable for all patients due to unfavorable side effect profiles [14]. In case of severe pain, advanced therapeutic options such as spinal cord stimulation should be considered.

Alternative treatments such as acupuncture and vitamin supplements may be suitable and effective for long-term pain relief or as a preferred patient choice.

The prognosis of DN is improves with optimal management of the underlying DM. Tight glycemic control and reduction of hyperglycemia can reduce symptoms and allow potential recovery. Quality care of patients with DN is essential to prevent serious complications such as foot ulcers, most commonly associated with DPN [9].

Prognosis may differ between types of DN, as studies suggest increased mortality associated with autonomic neuropathy, and increased risks of silent MI and death in patients with cardiovascular autonomic neuropathy, especially in combination with impaired heart rate variability. Contributions of additional contributing factors in this patient group is however unclear to date. Other types of DN, such as cranial neuropathy, truncal mononeuropathy, mononeuropathies, and diabetic amyotrophy may gradually improve if managed appropriately.

Risk factors promoting disease progression and severity include poor glycemic control, total hyperglycemic exposure, age, elevated lipid levels, hypertension, duration of DM, dyslipidemia, smoking, alcohol intake, increased height, and genetic factors such as the HLA-DR3/4 phenotype [2] [3].

As patients with either type 1 or type 2 primary DM, as well as those with secondary diabetes due to other underlying illnesses present with DPN, a common etiologic mechanism can be assumed. The Diabetes Control and Complications Trial (DCCT) strongly supports chronic hyperglycemia as cause or contributing factor [4].

Diabetes-related neuropathies may affect about 60-70% of DM patients, making diabetes the most common cause of DPN [5] [6]. Patients with type 1 DM typically develop DPN 10 or more years after diagnosis of DM, while neuropathy associated with type 2 DM may be present at disease onset.

Evidence from animal and in vitro research indicates that the pathogenesis of DN is based on metabolic and vascular factors. Disturbances of the glucose metabolism may be caused by enzymatic pathways such as redox imbalance associated with aldose reductase activity, impaired protein kinase C activity, perturbed cyclooxygenase activity associated with changes in prostaglandin metabolism or alterations in mitogen-activated protein kinase. Nonenzymatic pathways involved in pathophysiology of DN include increased oxidative and nitrosative stress, nonenzymatic glycation of structural nerve protein, impaired nitric oxide synthesis and endothelial dysfunction, hypoxia and ischemia of nerve trunks and ganglia, deficiencies in neurotrophic support and in C-peptide. Additional cellular factors include increased chronic inflammation and impaired nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathways, activation of poly (ADP-ribose) polymerase (PARP) and transcription factors, and oxidized LDL-mediated injury.

Related or common mechanisms, such as endothelial dysfunction, low-grade inflammation and rheological abnormalities, might also contribute to micro- and macro-vascular disease in people with type 2 DM [7] [8].

These dysfunctions or alterations lead to impaired mitochondrial function and reduced neurotrophic support. Subsequent injury of neurons and Schwann cells leads to disease progression by continuous neuronal damage and ultimate sensory impairment due to loss of peripheral nerve fibers [7].

The most effective preventive strategy for DN in all people with DM is continuous and tight control of hyperglycemia [15]. Multifactorial treatment of people with type 2 DM and its effect of DN incidence rates remains unclear to date [16].

Diabetic neuropathies (DN) pose a potentially serious complication in up to 50% of diabetes mellitus (DM) patients of either type 1 or 2. While type 2 DM patients might present with neuropathies at the time of prognosis or shortly thereafter, symptoms of DN usually occur in type 1 DM patients after chronic prolonged hyperglycemia.

DN are defined by presence of diabetes-mediated symptoms and/or peripheral nerve dysfunction, and significantly impact patient quality of life [1]. While primary symptoms can be mild, subsequent secondary complications can include falls, cardiac arrhythmias, foot ulcers, and ileus potentially leading to fractures, amputations and death. Timely prognosis of diabetic peripheral neuropathy (DPN) is therefore essential to prevent disease progression and complications.

Testing for development of DPN hould commence during diagnosis of DM, using available lists of potential symptoms. Screening of patients should include electrophysiologic testing, such as nerve conduction test and needle electromyography of distal muscles. Management of DM should include education of affected patients by their primary care providers to raise awareness of potential acute and chronic complications, including DPN. Development of DPN requires more frequent follow-ups and increased self-management.

DN can affect different types of nerves and vary in location. DPN affects peripheral nerves, typically those of feet and legs, while diabetic proximal neuropathy is characterized by nerve damage in the thighs, hips and buttocks. Diabetic autonomic neuropathy describes dysfunctions of the autonomic nervous system, affecting gastrointestinal system, urinary system, genital, or vascular systems. Diabetic focal neuropathy refers to nerve damage in a specific site or area in any part of the body.

Due to potentially overlapping symptoms or disease progression, differential diagnosis of the different types of diabetic neuropathies is recommended.

Diabetic neuropathy affects people with diabetes. It describes nerve damage due to having diabetes. Diabetic peripheral neuropathy, one form of diabetic neuropathy, affects the arms, hands, fingers, legs and feet. It is different from peripheral arterial disease or circulation problems, which might have similar symptoms but are caused by problems with the blood vessels rather than by nerve damage.

Diabetic neuropathy can damage different types of nerves, such as sensory nerves, motor nerves or autonomic nerves. Sensory nerves are necessary to feel temperature, pain, and other sensations. Motor nerves control muscles and movement while autonomic nerves are responsible for involuntary functions, such as sweating.

Especially in type 1 diabetes, diabetic peripheral neuropathy develops over time, and people might have diabetes for more than 10 years before it is diagnosed. In other cases, such as in those people with type 2 diabetes, it might be diagnosed at the same time as diabetes. In general, having diabetes for many years increases the risk of developing diabetic peripheral neuropathy.

Patients with diabetic peripheral neuropathy are more likely to develop skin ulcers, which are open sores prone to infections. In case of poor wound healing and recurrent or continuous infections, these complications of diabetic peripheral neuropathy can lead to amputation of a foot or a leg, or to death in worst cases.

Causes

Diabetic peripheral neuropathy is more common in diabetes patients with poor control of blood sugar levels and frequent fluctuations. However, it can also develop in those patients with well-managed blood glucose levels. Although the direct link between diabetes and diabetic peripheral neuropathy is not entirely clear, theories suggest that high blood glucose levels or constricted blood vessels can cause nerve damage.

Causes for developing sores, a serious complication of diabetes, include deformities, numbness and cracked skin. Here, motor neuropathy can lead to the development of deformities such as bunions or hammertoes. These might rub and cause sores when wearing shoes, but due to numbness and reduced perception of specific pain, these sores as well as possible skin cuts might go unnoticed. Likewise, cracked skin, which can be caused by autonomic neuropathy, can lead to the development of sores. Sores that are untreated might become infected.

Symptoms

Symptoms can vary and depend on the type(s) of nerves involved. The most common symptoms associated with all types of diabetic neuropathy are pain and numbness. Other symptoms include tingling or discomfort in the feet, or prickly, sharp pain and burning feet in the case of sensory neuropathy. Motor neuropathy typically causes muscle weakness and loss of muscle tone in feet and legs, loss of balance and possibly deformities (changes in foot shape). Symptoms of autonomic neuropathy include cracked skin and dry feet.

Diagnosis

Diagnosis of diabetic peripheral neuropathy is usually made by a foot and ankle surgeon after a range of simple tests that evaluate the patient's perception of touch, pain, vibration, and temperature as well as his/her reflexes in feet and lower legs. Other neurological tests might be necessary to confirm the diagnosis.

Treatment

The best and most effective treatment of diabetic peripheral neuropathy is tight control of blood sugar levels. Additional treatments for pain relief and other symptoms, such as tingling or burning, may be used. These treatments may be used in combination to increase effectiveness. Physical therapy may helpful in some patients with other symptoms.

1. Boulton AJ, Malik RA. Diabetic neuropathy. Med Clin North Am. 1998 Jul; 82(4):909-29.
2. Dorsey RR, Eberhardt MS, Gregg EW, et al. Control of risk factors among people with diagnosed diabetes, by lower extremity disease status. Prev Chronic Dis. 2009 Oct; 6(4):A114.
3. Tavakkoly-Bazzaz J, Amoli MM, Pravica V, et al. VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep. 2010; 37(7):3625-30.
4. Diabetes control and complications trial research group. 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.
5. Charnogursky G, Lee H, Lopez N. Diabetic neuropathy. Handb Clin Neurol. 2014; 120:773-85.
6. Said G. Diabetic neuropathy. Handb Clin Neurol. 2013; 115:579-89.
7. Sullivan KA, Feldman EL. New developments in diabetic neuropathy. Curr Opin Neurol. 2005; 18:586-590.
8. Rosenson RS, Fioretto P, Dodson PM. Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis. 2011; 218:13-18.
9. 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. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837-853.
11. Thurman DJ, Stevens JA, Rao JK; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: assessing patients in a neurology practice for risk of falls (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2008; 70:473-479.
12. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010; 17:903-912.
13. Skyler JS. Diabetic complications. The importance of glucose control. Endocrinol Metab Clin North Am. 1996 Jun. 25(2):243-54.
14. Chou R, Carson S, Chan BK. Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials. J Gen Intern Med. 2009; 24(2):178-88.
15. Ang L, Jaiswal M, Martin C, et al. Glucose control and diabetic neuropathy: lessons from recent large clinical trials. Curr Diab Rep. 2014; 14:528.
16. Charles M, Ejskjaer N, Witte DR, et al. Prevalence of neuropathy and peripheral arterial disease and the impact of treatment in people with screen-detected type 2 diabetes: the ADDITION-Denmark study. Diabetes Care. 2011; 34:2244-2249.