Diabetic neuropathy

Diabetic neuropathy is various types of nerve damage associated with

Diabetic neuropathy can affect any peripheral nerves including sensory neurons, motor neurons, and the autonomic nervous system. Therefore, diabetic neuropathy has the potential to affect essentially any organ system and can cause a range of symptoms. There are several distinct syndromes based on the organ systems affected.^{[citation needed]}

Sensorimotor polyneuropathy

Longer nerve fibers are affected to a greater degree than shorter ones because

Gastrointestinal manifestations include gastroparesis, nausea, bloating, and diarrhea. Because many diabetics take oral medication for their diabetes, absorption of these medicines is greatly affected by the delayed gastric emptying. This can lead to hypoglycemia when an oral diabetic agent is taken before a meal and does not get absorbed until hours, or sometimes days later when there is normal or low blood sugar already. Sluggish movement of the small intestine can cause bacterial overgrowth, made worse by the presence of hyperglycemia. This leads to bloating, gas and diarrhea.^{[citation needed]}

Urinary symptoms include urinary frequency, urgency,

Vascular and neural diseases are closely related.

Advanced glycated end products

Elevated levels of glucose within cells cause a non-enzymatic covalent bonding with proteins, which alters their structure and inhibits their function. Some of these glycated proteins have been implicated in the pathology of diabetic neuropathy and other long-term complications of diabetes.

Polyol pathway

Also called the sorbitol/aldose reductase pathway, the polyol pathway appears to be implicated in diabetic complications, especially in microvascular damage to the

Diabetic peripheral neuropathy can be diagnosed with a history and physical examination. The diagnosis is considered in people who develop pain or numbness in a leg or foot with a history of diabetes. Muscle weakness, pain, balance loss, and lower limb dysfunction are the most common clinical manifestations.[5] Physical exam findings may include changes in appearance of the feet, presence of ulceration, and diminished ankle reflexes. The most useful physical examination finding for large fiber neuropathy is an abnormally decreased vibration perception to a 128-Hz tuning fork (likelihood ratio (LR) range, 16–35) or pressure sensation with a 5.07 Semmes-Weinstein monofilament (LR range, 11–16). Normal results on vibration testing (LR range, 0.33–0.51) or monofilament (LR range, 0.09–0.54) make large fiber peripheral neuropathy from diabetes less likely.^[6] Nerve conduction tests may show reduced functioning of the peripheral nerves, but seldom correlate with the severity of diabetic peripheral neuropathy and are not appropriate as routine tests for the condition.^[7] Small fiber neuropathy measured by QST and Sudomotor function tests, through electrochemical skin conductance, is more and more indicated to assess early signs of diabetic neuropathy^[8][9][10] and autonomic neuropathy.^[11]

Classification

Diabetic neuropathy encompasses a series of different neuropathic syndromes which can be categorized as follows:^[12]

• Focal and multifocal neuropathies:
  • Mononeuropathy which affects one nerve
  • Amyotrophy or radiculopathy such as proximal diabetic neuropathy, affecting a specific pattern of nerves
  • Multiple lesions, affecting nerves that don't follow a specific pattern, also called "mononeuritis multiplex"
  • Nerve damage from entrapment (e.g. median, ulnar, peroneal)
• Symmetrical neuropathies:
  • Sensory
  • Autonomic
  • Distal symmetrical polyneuropathy (DSPN), the diabetic type of which is also known as diabetic peripheral neuropathy (DPN) (most common presentation)

Prevention

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Diabetic neuropathy can be largely prevented by maintaining blood glucose levels and lifestyle modifications.^[13][14] Enhanced glucose control methods include more frequent subcutaneous insulin administration, continuous insulin infusion, oral antidiabetic agents, while lifestyle modifications may include exercise alone, or in combination with dietary modifications. Enhanced glucose control prevents the development of clinical neuropathy and reduces nerve abnormalities in type 1 diabetes, and delays the onset of neuropathy in both types of diabetes. However, such methods may increase the likelihood of experiencing a hypoglycemic event, and many of these more aggressive methods require more frequent insulin use which has been associated with excessive risk of falls.^[15]

Treatment

Blood glucose management

Treatment of early manifestations of sensorimotor polyneuropathy involves improving glycemic control.^[16] Tight control of blood glucose can reverse the changes of diabetic neuropathy if the neuropathy and diabetes are recent in onset. This is the primary treatment of diabetic neuropathy that may change the course of the condition as the other treatments focus on reducing pain and other symptoms.

Topical agents

Capsaicin applied to the skin in a 0.075% concentration has not been found to be more effective than placebo for treating pain associated with diabetic neuropathy. There is insufficient evidence to draw conclusions for more concentrated forms of capsaicin, clonidine, or lidocaine applied to the skin.^[17] About 10% of people who use capsaicin cream have a large benefit.^[18]

Medications

Medication options for pain control include antiepileptic drugs (AEDs),

The only three medications approved by the United States' Food and Drug Administration for diabetic peripheral neuropathy (DPN) are the antidepressant duloxetine, the anticonvulsant pregabalin, and the long-acting opioid tapentadol ER (extended release).^[22][23] Before trying a systemic medication, some doctors recommend treating localized diabetic peripheral neuropathy with lidocaine patches.^[7]

Antiepileptic drugs

Multiple guidelines from medical organizations such as the

As above, the serotonin-norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine are recommended in multiple medical guidelines as first or second-line therapy for DPN.[24] A 2017 systematic review and meta-analysis of randomized controlled trials concluded there is moderate quality evidence that duloxetine and venlafaxine each provide a large benefit in reducing diabetic neuropathic pain.^[17] Common side effects include dizziness, nausea, and sleepiness.^[17]

Tricyclic antidepressants

TCAs include

Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties.^[17] Opioid medications are recommended as second or third-line treatment for DPN.^[24]

Medical devices

Monochromatic infrared photo energy treatment (MIRE) has been shown to be an effective therapy in reducing and often eliminating pain associated with diabetic neuropathy.^{[citation needed]} The studied wavelength of 890 nm is able to penetrate into the subcutaneous tissue where it acts upon a specialized part of the cell called the cytochrome C. The infrared light energy prompts the cytochrome C to release nitric oxide into the cells. The nitric oxide in turn promotes vasodilation which results in increased blood flow that helps nourish damaged nerve cells. Once the nutrient rich blood is able to reach the affected areas (typically the feet, lower legs and hands) it promotes the regeneration of nerve tissues and helps reduce inflammation thereby reducing and/or eliminating pain in the area.

Gait training, posture training, and teaching these patients the basic principles of off-loading can help prevent and/or stabilize foot complications such as foot ulcers.^[26] Off-loading techniques can include the use of mobility aids (e.g. crutches) or foot splints.^[26] Gait re-training would also be beneficial for individuals who have lost limbs, due to diabetic neuropathy, and now wear a prosthesis.^[26]

Exercise programs, along with manual therapy, will help to prevent muscle contractures, spasms and atrophy. These programs may include general muscle stretching to maintain muscle length and a person's range of motion.^[28] General muscle strengthening exercises will help to maintain muscle strength and reduce muscle wasting.^[29] Aerobic exercise such as swimming and using a stationary bicycle can help peripheral neuropathy, but activities that place excessive pressure on the feet (e.g. walking long distances, running) may be contraindicated.^[30] Exercise therapy has been shown to increase the blood flow to the peripheral nerves, can improve gait function.^[31]

Heat,

Low-quality evidence supports a moderate-large beneficial effect of botulinum toxin injections.^[17] There is insufficient evidence to draw firm conclusions for the utility of the cannabinoids nabilone and nabiximols.^[17]

Prognosis

The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive.

As a complication, there is an increased risk of injury to the feet because of loss of sensation (see

Globally diabetic neuropathy affects approximately 132 million people as of 2010 (1.9% of the population).[33]

Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of

The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height, and hyperlipidemia are also risk factors for diabetic neuropathy.

References