Diabetes neuropathy

Notes

## Basic introduction:

  • Diabetic neuropathies (DN) result from diabetic microvascular injury involving vasa nervorum (small blood vessels that supply nerves) as well as macrovascular conditions that can end up with diabetic neuropathy.
  • DN affects all peripheral nerves including motor neurons, the autonomic nervous system and pain fibers, among others.

## Epidemiology and Statistics:

  • Overall all 15% of individuals with diabetes mellitus will have foot ulcer during their lifetime
  • The annual global incidence of foot ulcers among diabetes mellitus is 2-3%
  • About 60-70% of diabetics have mild to severe forms of nervous system damage
  • Prevalence of Diabetes neuropathy in Sub-Saharan Africa ranges from 27% to 66%
  • > 60% of nontraumatic lower-limb amputations in the USA occur among people with diabetes due to DN
  • 70% of people die five years following an amputation
  • 49-85% of amputations can be prevented
  • In developing countries foot problems account for 40% of healthcare resources and 15% in developed countries.
  • Diabetes amputations has a 5 year mortality rate of 39 - 68% with a below knee amputation, and 89% with a single above knee amputation
  • Patients with a previous below knee amputation have a 42% chance of a contra lateral same level amputation within 1-3 years and 56% chance at 3 to 5 years.
  • Patients with bilateral below knee amputations have an 80% mortality rate at 2 years
  • ≥25% of men with diabetes have erectile dysfunction due to diabetes neuropathy

## Classification of DN:

  • Autonomic neuropathy

_It affects the autonomic nerves controlling internal organs in the genitourinary, gastrointestinal and cardiovascular systems as well as the peripheral autonomic nerves.

_Peripheral autonomic neuropathy presents with the following symptoms/signs: Neuropathic arthropathy (Charcot’s foot), aching, pulsation, tightness, cramping, dry skin, pruritus, edema, sweating abnormalities, weakening of the bones in the foot leading to fractures

_Peripheral autonomic neuropathy is tested by direct microelectrode recording of postganglionic C fibers, Galvanic skin responses, and measurement of vascular responses

_Genitourinary autonomic neuropathy manifests as bladder dysfunction, retrograde ejaculation, erectile dysfunction, and dyspareunia

_Gastrointestinal autonomic neuropathy manifests as gastroparesis (delayed gastric emptying) that can lead to anorexia, nausea, vomiting, and early satiety. Gastrointestinal autonomic neuropathy can also manifest as diabetic enteropathy that can lead to diarrhea and constipation

_Cardiovascular autonomic neuropathy manifests as exercise intolerance and postural hypotension

_Gustatory sweating (sweating on the forehead, face, scalp, and neck occurring soon after ingesting food)

  • Polyradiculopathy

_Polyradiculopathy is the damage of the multiple nerve roots that is sufficient to produce neurologic symptoms and signs such as pain, weakness, and sensory loss

_The common types of polyradiculopathy include: Lumbar polyradiculopathy (diabetic amyotrophy), thoracic polyradiculopathy and Diabetic neuropathic cachexia

_Lumbar polyradiculopathy (diabetic amyotrophy) is characterized by thigh pain followed by muscle weakness and atrophy

_Thoracic polyradiculopathy is characterized by severe pain on one or both sides of the abdomen, mostly in a band-like pattern

_Diabetic neuropathic cachexia is a combination of polyradiculopathy and peripheral neuropathy that is characterized by weight loss and depression.

_Diagnosis of polyradiculopathy is by Electromyographic (EMG) examination.

  • Mononeuropathy

_This is one of the members of focal and multifocal neuropathies:

_The two main classes of mononeuropathy are: peripheral mononeuropathy and cranial mononeuropathy

_Peripheral mononeuropathy occurs due to a single nerve damage, as a result of compression or ischemia, and it is characterized by numbness, edema, pain and prickling (or tickling) in the wrist (carpal tunnel syndrome), elbow, and/or foot (unilateral foot drop).

_Cranial mononeuropathy is known to affect the 12 pairs of nerves that are connected with the brain and control sight, eye movement, hearing, and taste. It manifests as unilateral pain adjacent to the affected eye, double vision, and paralysis of the eye muscle

  • Symmetric polyneuropathy

­_It is further classified into acute sensory DN, autonomic DN and distal symmetrical polyneuropathy (of which diabetic peripheral neuropathy is the most common presentation).

_It is the most common form of DN

_It affects distal lower extremities and hands (“stocking-glove” sensory loss)

_Its symptoms and signs include pain, loss of vibratory sensation, paresthesia, and dysesthesia (which is unpleasant sensation, such as pain, burning, or tingling when a part of the body is touched)

_Complications of symmetric polyneuropathy include ulcers, Charcot arthropathy (which is a progressive degeneration of a weight bearing joint that is marked by bony destruction, bone resorption, and eventual deformity), dislocation and stress fractures, and amputation.

## Pathology DN:

  • Microvascular disease (microangiopathy) and related ischemia
  • Hypertension
  • Advanced glycation end products
  • Defects in polyol or sorbitol pathway
  • Dyslipidemia

## Risk factors for DN:

  • Standard of glucose control
  • Duration of diabetes
  • Excessive alcohol
  • Being of tall stature
  • Lifestyle factors (such as smoking and diet)
  • Injury to nerves (e.g. mechanical injury)
  • Injury to blood vessels
  • Above 40yrs old
  • Coronary heart disease
  • Genetic predisposition
  • Autoimmune factors
  • Risk factors for amputation include:

_Peripheral neuropathy with loss of protective sensation

_Altered biomechanics (with neuropathy)

_Evidence of increased pressure

_Peripheral vascular disease

_History of ulcers or amputation

_Severe nail pathology

Symptoms
  • Anorgasmia
  • Burning or electric pain
  • Diarrhea
  • Difficulty swallowing
  • Dizziness
  • Dysesthesia
  • Erectile dysfunction
  • Facial, mouth and eyelid drooping
  • Fasciculation
  • Muscle weakness
  • Numbness and tingling of extremities (carpal tunnel syndrome is part of it)
  • Retrograde ejaculation (in males)
  • Speech impairment
  • Trouble with balance
  • Urinary incontinence
  • Vision changes
  • Slowed digestion of food in the stomach
Diagnosis
  • Clinical evaluation
  • Comprehensive foot exam
  • Skin sensation and skin integrity Quantitative Sensory Testing (QST)
  • X-ray
  • Ultrasound
  • Nerve conduction studies
  • Electromyographic examination (EMG)
Differential
  • Vitamin B12 deficiency
  • Osteoarthritis
  • Hypothyroidism
  • Uremic syndrome
  • Peripheral vascular disease
  • Toxins due to alcohol and occupational
  • Malignancies
  • Amyloidosis
  • AIDS
  • Cauda equina syndrome (Spinal cord disease)
Prevention
  • Regular screening for cardiovascular diseases
  • Close monitor for glucose levels
  • Regular examination of foot in patient with neuropathy
Reference
  1. American Diabetes Association: Preventive Foot Care in Diabetes (Position Statement). Diabetes Care 27 (Suppl.1): S63-S64, 2004
  2. Feldman, EL: Classification of diabetic neuropathy. In UpToDate. Wellesley, MA, UpToDate, 2003
  3. International Diabetes Federation (2012). The Global Burden. IDF Diabetes Atlas Fifth Edition.
  4. Kenyan Ministry of Health. Clinical guidelines for management and referral of common conditions at levels 4-6. Hospitals. 2009; 3:259-261.http://apps.who.int/medicinedocs/documents/s21000en/s21000en.pdf
  5. Ministry of Health, Kenya. Kenya Essential Medicine List (2016). http://publications.universalhealth2030.org/uploads/KEML-2016Final-1.pdf
  6. National Diabetes Information Clearinghouse. Diabetic Neuropathies: The Nerve Damage of Diabetes. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), DHHS; 2002
  7. National Diabetes Information Clearinghouse. Prevent Diabetes Problems: Keep Your Feet and Skin Healthy. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), DHHS; 2003
  8. Rutkove SB, Tarulli A. Polyradiculopathy: Spinal stenosis, infectious, carcinomatous, and inflammatory nerve root syndromes. UpToDate. July 24, 2013.
Management
  • Management depends on the class and type of neuropathy:

_Peripheral autonomic neuropathy is managed by appropriate Foot care (like elevation of feet when sitting), avoiding aggravating drugs, diuretics to reduce edema and wearing of support stockings as well as regular screening for cardiovascular diseases

_Genitourinary autonomic neuropathy symptoms are managed as follows: bladder dysfunction by voluntary urination or catheterization, retrograde ejaculation by antihistamines such chlorpheniramine, erectile dysfunction by use of PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil, and dyspareunia by use of lubrication creams and estrogen cream

_Gastrointestinal autonomic neuropathy symptoms are managed as follows: gastroparesis by ruling out other causes first, small and frequent meals and metoclopramide or erythromycin.  Diarrhea is managed by loperamide, and constipation by stool softeners or dietary fiber

_Cardiovascular autonomic neuropathy symptoms are managed as follows: discontinuing aggravating medicines, changing the posture slowly and using elevated bed, and increasing plasma volume.

_ Polyradiculopathy symptoms are managed by observing appropriate foot care, control of glucose and analgesics

  • Effective control of diabetes
  • Pain control with tricyclic antidepressants (mainly venlafaxine 75-225mg/day, duloxetine 60-120mg/day and amitriptyline 25-100mg/day), topical creams and anticonvulsants (pregabalin, gabapentin 900-3600mg/day and sodium valproate 500-1200mg/day)
  • Foot care
  • Weight control
  • Transcutaneous Electrical Nerve Stimulation (TENS) 3-4 weeks
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