One of the most feared and common complications of diabetes mellitus is diabetic neuropathy. It affects around 50% of all patients diagnosed with type 1 and type 2 diabetes, and is characterized by progressive dysfunction of the peripheral nerves. Diabetic neuropathy is the primary etiology behind diabetic foot ulcer and its complications. Therefore, its early detection and management by podiatrists and wound care specialists can help improve wound care outcomes in patients with diabetes. 

What Is Diabetic Neuropathy?

Patients with diabetes mellitus are at an increased risk of peripheral nervous system dysfunction which is termed diabetic neuropathy. Even though the prevalence of peripheral nerve damage is common in patients with diabetes, it should only be diagnosed after the exclusion of other causes that cause peripheral nerve damage. Diabetic neuropathy is not a single entity and refers to a group of disorders that affect the peripheral and autonomic nervous systems in patients with diabetes. The most common form of diabetic neuropathy is "distal symmetric polyneuropathy"  which is characterized by the loss of sensation in the lower limbs. It presents with a "pins and needle sensation" in the lower limbs with a progressive loss of sensation and function. This form of diabetic neuropathy is implicated in the pathogenesis and development of diabetic foot ulcers with impaired wound healing. Therefore, glycemic control and management of diabetic neuropathy form an essential component of diabetic wound care.

Symptoms Of Diabetic Neuropathy 

The signs and symptoms of diabetic neuropathy depend on the specific subtype of diabetic neuropathies. The major recognized types of diabetic neuropathies and their presenting symptoms are described as  follows:

• Symmetric polyneuropathy: It is the most common type of nerve disorder in diabetic patients. The word diabetic neuropathy is synonymous with this type. It presents with a typical "stocking-glove" sensory loss in the lower extremities. The severe forms of symmetric polyneuropathies also affect the motor axons and can cause motor weakness. 
  

• Autonomic Neuropathy: Due to the unspecific nature of the symptoms, autonomic neuropathy mostly goes unnoticed. However, it is a serious complication of diabetes and causes autonomic dysfunction. Patients can present with orthostatic hypotension, exercise intolerance, sleep apnea, and gastroparesis. It is associated with an increased risk of mortality.

• Polyradiculopathies: These are characterized by injury to the proximal nerve roots. Patients are generally older and present with weakness or atrophy in the region supplied by the affected nerve roots. 

• Cranial mononeuropathy: Patients with diabetes mellitus can have involvement of cranial nerves. Cranial mononeuropathies present with ‍

• Peripheral mononeuropathy: Median nerve mononeuropathy is the most common peripheral neuropathy in diabetic patients. It is also known as the "carpal tunnel" syndrome and presents with numbness or tingling in the hand. 

What Causes Diabetic Neuropathy?

The pathogenesis of diabetic neuropathy is not properly understood but is generally regarded as a multifactorial process. The major factors implicated in the development of diabetic neuropathy include reactive oxygen species, polyol pathway, and advanced glycation end products.

In the presence of hyperglycemia, excessive levels of glucose are present in the nerves which are shunted into the polyol pathway. As a result, fructose and sorbitol accumulate inside the nerve fiber which affects the propagation of action potential through disruption of sodium-potassium pump activity. The increase in the production of free radicals also causes damage to blood vessels supplying the nerves leading to ischemic injury. Excess glucose combines with proteins, lipids, and nucleotides leading to the production of advanced glycation end-products. These products disrupt nerve integrity and function, contributing to the development of diabetic neuropathy.

Management Of Diabetic Neuropathy 

Diabetic neuropathy affects wound healing and should therefore be properly diagnosed and managed by podiatrists and wound care specialists. As diabetic foot ulcers are one of the leading causes of lower-limb amputations, primary care physicians should be vigilant to any early signs of diabetic neuropathic changes. The general principles for the management of diabetic neuropathy include:

• Glycemic Control: Optimal glycemic control can help limit the progression of diabetic neuropathy in patients with type 1 diabetes mellitus. Patients with type 2 diabetes mellitus can also benefit from glycemic control but effects are relatively modest. Patients should be informed about the importance of keeping their blood sugar levels at an optimal level and should be given appropriate lifestyle advice.

• Lifestyle Interventions: Lifestyle modifications form the cornerstone of type 2 diabetes mellitus treatment, and can help limit the progression of diabetic neuropathy. Patients should be advised to keep their body mass index within a healthy limit and should aim for 150 minutes of moderate-intensity exercise every week. 

• Correct B12 Deficiency: B12 deficiency is a common cause of peripheral neuropathy and can be aggravated by metformin intake. Therefore, patients presenting with peripheral neuropathy symptoms should be screened for B12 deficiency.

• Pain Control: Patients with diabetic neuropathy can present with burning, stabbing pain in the lower limbs which affects around 15 to 20% of patients. As neuropathic pain can be severe and does not respond to routine analgesics, it is usually treated with antidepressant medications. These include amitriptyline, duloxetine, venlafaxine, or anti-seizure drugs like gabapentin or pregabalin. Pregabalin is an effective alternative to first-line antidepressant medications.

Diabetic neuropathies are irreversible and can be debilitating. However, early intervention and management can help limit the progression of the disease. Treatment of diabetic neuropathy is also effective in limiting ulcer recurrence and therefore can help lower the rate of diabetic foot-related amputations.