Diabetic Neuropathy Signs and Symptoms

Definition

• Group of progressive, degenerative conditions involving autonomic, motor, or sensory peripheral nerves that develops in patients with diabetes mellitus (DM) and cannot be attributed to other causes of peripheral neuropathy
  • Diagnosis of exclusion
• Pathogenesis is multifactorial and mainly due to oxidative and inflammatory stress in association with metabolic dysfunction causing nerve cell damage

Dịch tễ học

• Affects about 50% of DM patients
• More common in adults >50 years of age
• More common in patients with type 2 DM

Yếu tố nguy cơ

Unmodifiable Risk Factors

• Advanced age
• Duration of diabetes
  • Risk of developing neuropathy increases with duration of diabetes and age
• Height
  • Independent predictor of neuropathy in both type 1 and type 2 DM patients

Modifiable Risk Factors

• Hyperglycemia
• Abdominal obesity
• Dyslipidemia
  
  • Hypertriglyceridemia increases the occurrence of diabetic sensorimotor polyneuropathy (DSPN) by 2.1 times
  • Increased levels of low-density lipoprotein cholesterol (LDL-C)
  • Decreased high-density lipoprotein cholesterol (HDL-C)
• Hypertension
• Obesity
  
  • Body mass index (BMI), weight, and waist circumference are associated with neuropathy
• Smoking
• Heavy alcohol consumption

Signs and Symptoms

DSPN

• Fifty percent of patients are asymptomatic
• Early symptoms are due to small-fiber involvement followed by large-fiber impairment
• Patients have either pain or negative symptoms or both
  • Small-nerve dysfunction symptoms include pain and dysesthesia which is characterized as unpleasant sensations of burning and tingling
  • Painful DSPN may be described as sensation of electricity, shooting pain, contact hyperalgesia, burning, lancinating or tingling and tends to occur or worsen at night
    • Pain may be elicited from contact such as contact with socks, shoes and bedclothes
    • Present in 13-26% of patients with DM
  • Negative symptoms include selective loss of temperature and pain sensation

• Large-fiber dysfunction may present as numbness, tingling without pain, and loss of protective sensation (LOPS) which can be a risk factor for diabetic foot ulceration
  • Described by patients as a feeling of their feet wrapped in wool or walking on thick socks
  • Risk factor for falls due to disturbance in gait

• Muscular symptoms include muscle weakness, atrophy, balance problems and ataxic gait
• “Stocking-glove”-like distribution of neuropathic symptoms are present in patients with long-term diabetes
• Neuropathic pain is usually worse at night and may interfere with daily activities and reduce sleep quality and quality of life

Diabetic Autonomic Neuropathies

• Clinical manifestations include hypoglycemia unawareness, resting tachycardia, orthostatic hypotension, gastroparesis, constipation, diarrhea, fecal incontinence, erectile dysfunction, neurogenic bladder, cracking of skin or peripheral dryness, and sudomotor dysfunction with either increased or decreased sweating

• Cardiovascular autonomic neuropathy (CAN)
  
  • Asymptomatic in the early phase
  • May present as exercise intolerance, fatigue, syncope or dizziness, persistent sinus tachycardia, decreased heart rate variability, bradycardia and supine hypertension
  • Orthostatic hypotension may occur as a result of vasomotor neuropathy

• GI autonomic neuropathy
  
  • Most common symptoms are gastroparesis, dysphagia, diabetic diarrhea, fecal incontinence and constipation
  • Delayed esophageal transit occurs in 50% of patients and gastroparesis occurs in 40% of patients with long-term diabetes
    
    • Gastroparesis can lead to dysphagia, regurgitation, esophageal erosion and strictures
    • Delayed gastric emptying and gastric retention can lead to early satiety, cramping, bloating, epigastric pain or heartburn, nausea, vomiting, and appetite loss which in turn can lead to anorexia
    • May lead to medication malabsorption and possibility of hypoglycemia
  • Impairment of the colon may lead to severe constipation, diarrhea and fecal incontinence

• Urogenital autonomic neuropathy
  
  • May manifest as erectile dysfunction which is present in 35-90% of men with DM and/or retrograde ejaculation
  • May cause vaginal dryness, dyspareunia and decreased libido in women with DM
  • Bladder dysfunction is often observed in type 1 DM than type 2 DM patients
    
    • Bladder sensation impairment may lead to retention and incomplete emptying of urine, overflow incontinence, and urinary tract infections (UTI)
    • Most common symptoms include dysuria, frequency, urgency, nocturia, incomplete voiding, weak urinary stream and urinary incontinence

• Diabetic sudomotor dysfunction
  
  • Presents as dry skin, anhidrosis or heat intolerance
  • Initial manifestation is global anhidrosis due to thermoregulatory sweating loss
  • May also present with hyperhidrosis, gustatory sweating, and abnormal sweat production on the face, head, neck, shoulders and chest after food consumption

• Treatment-induced neuropathy
  
  • Manifests as severe burning pain, hyperalgesia or allodynia, and signs and symptoms of autonomic dysfunction within days to weeks after rapid glycemic control

• Diabetic neuropathic cachexia
  
  • Manifest as unintentional severe weight loss (10% weight loss from baseline body weight)

• Cranial mononeuropathies
  
  • Diabetic oculomotor palsy will present as third nerve palsy with pupillary sparing

• Peripheral nerve neuropathies
  
  • with acute onset but self-limited course resolving within 2 months
  • May occur during periods of transition in the diabetic illness such as after an episode of hypoglycemia or hyperglycemia, during insulin dosage adjustment, or when there is rapid weight loss
  • Usually presents with pain

• Entrapment neuropathies
  
  • Often asymptomatic and discovered only during nerve conduction studies
  • Carpal tunnel syndrome symptoms include numbness, pain, or tingling in the area innervated by the median nerve
    
    • Thenar muscle wasting may be observed especially in the elderly patients with DM but motor weakness is not common

• Diabetic radiculoplexus neuropathies
  
  • Symptoms include unilateral or multiple asymmetrical neuropathic pain and may lead to muscle weakness and atrophy
  • Diabetic cervical radiculoplexus neuropathy presents with pain accompanied by weakness which may affect the whole brachial plexus or upper limbs
    
    • Usually unilateral presentation but may progress to bilateral
  • Diabetic thoracic radiculoneuropathy presents with chronic abdominal pain
  • Diabetic lumbosacral radiculoplexus neuropathy symptoms begin abruptly, unilaterally and proximally and presents with severe, deep thigh pain progressing to weakness and muscle atrophy which is often debilitating