Diabetic Neuropathy Initial Assessment

Clinical Presentation

Diabetic Sensorimotor Polyneuropathy  

Fifty percent of diabetic sensorimotor polyneuropathy 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 are characterized as unpleasant sensations of burning and tingling. Painful diabetic sensorimotor polyneuropathy may be described as a 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 socks, shoes, or bedclothes. This is 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. It is described by patients as a feeling of their feet being wrapped in wool or as if walking on thick socks. This poses as a risk factor for falls due to disturbances in gait. Muscular symptoms may include muscle weakness, atrophy, balance problems, and ataxic gait. A “stocking-glove”-like distribution of neuropathic symptoms is commonly seen in patients with long-term diabetes. Neuropathic pain is usually worse at night and may interfere with daily activities, reduce sleep quality, and negatively impact overall quality of life.  

Diabetic Autonomic Neuropathies  

Clinical manifestations of diabetic autonomic neuropathies include hypoglycemia unawareness, resting tachycardia, orthostatic hypotension, gastroparesis, constipation, diarrhea, fecal incontinence, erectile dysfunction, neurogenic bladder, cracking of the skin or peripheral dryness, and sudomotor dysfunction with either increased or decreased sweating. CAN is asymptomatic in its early phase but may present as exercise intolerance, fatigue, syncope or dizziness, persistent sinus tachycardia, decreased heart rate variability, bradycardia, and supine hypertension. Orthostatic hypotension may also occur as a result of vasomotor neuropathy.  

The most common symptoms of GI autonomic neuropathy are gastroparesis, dysphagia, diabetic diarrhea, fecal incontinence, and constipation. Delayed esophageal transit occurs in 50% of patients, while gastroparesis occurs in 40% of those with long-term diabetes. Gastroparesis can lead to dysphagia, regurgitation, esophageal erosion, and strictures. Additionally, 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. This may also lead to medication malabsorption and the possibility of hypoglycemia. Lastly, 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. In women with DM, it may cause vaginal dryness, dyspareunia, and decreased libido. Bladder dysfunction is more commonly observed in patients with type 1 DM than in those with type 2 DM. Bladder sensation impairment may lead to urine retention and incomplete emptying of urine, resulting in overflow incontinence and urinary tract infections (UTIs). The 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. The initial manifestation is typically global anhidrosis due to thermoregulatory sweating loss. It 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 manifests as unintentional severe weight loss (defined as a 10% loss from baseline body weight). Cranial mononeuropathies include diabetic oculomotor palsy that represents as third nerve palsy with pupillary sparing.  

Peripheral nerve neuropathies usually have an acute onset but follow a self-limited course resolving within 2 months. They may occur during periods of transition in the diabetic illness, such as after episodes of hypoglycemia or hyperglycemia, during insulin dosage adjustment, or during rapid weight loss. These conditions usually present with pain. Entrapment neuropathies are often asymptomatic and are discovered only during nerve conduction studies. Carpal tunnel syndrome presents with numbness, pain, or tingling in the area innervated by the median nerve. Thenar muscle wasting may also be observed, especially in elderly patients with DM, but motor weakness is not common. Diabetic radiculoplexus neuropathies are characterized by symptoms that 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. It usually presents unilaterally but may progress bilaterally. Diabetic thoracic radiculoneuropathy presents with chronic abdominal pain, while diabetic lumbosacral radiculoplexus neuropathy symptoms begin abruptly, unilaterally, and proximally, and presents with severe, deep thigh pain that progresses to weakness and muscle atrophy, which is often debilitating.

History

Medical and neurological history should focus on documenting diabetes management and identifying signs and symptoms of diabetic polyneuropathy and autonomic neuropathy. This includes reviewing the patient’s medication history, history of alcohol use, and other present medical conditions. A prior history of ulceration, amputation, Charcot foot, angioplasty or vascular surgery, cigarette smoking, retinopathy, and renal disease should be obtained to guide foot care as well as symptoms of peripheral arterial disease (PAD) such as leg fatigue, claudication, and rest pain relieved with dependency. It is also essential to inquire about symptoms of orthostatic intolerance (eg lightheadedness, dizziness, or weakness upon standing), syncope, exercise intolerance, or changes in sweat function. History of GI symptoms (eg dysphagia, odynophagia, abdominal pain, nausea, vomiting, feeling of fullness, bloating, diarrhea, constipation, fecal incontinence) should also be gathered. Similarly, history of micturition problems (eg urination per day, residual urine, palpable bladder, recurrent UTI, pyelonephritis, weak urinary stream, incontinence, straining, or use of abdominal muscles when urinating) should be noted. Targeted history questions are also necessary in patients with functional sexual disorders.  

Assessment of pain intensity typically uses tools such as visual analog scales (VAS) or numerical rating scales in clinical practice; however, these tools do not provide insight into the effect of pain on the patients’ functioning and well-being. The use of scales such as the brief pain inventory-DPN, which assesses pain interference, or the Norfolk Quality of Life–diabetic neuropathy which assesses the effects on quality of life, provide more relevant information to assess the need for treatment. The “Douleur Neuropathique en 4 Questions” (DN4-Interview) may be used to screen for neuropathic pain in diabetes.  

Evaluation and management of other factors that may affect pain perception and quality of life, which include the presence of mood or sleeping disorders, is recommended to help reduce pain and improve the quality of life. The functional impact or effect of pain on the patients’ functioning and well-being should be assessed at each visit to monitor therapeutic response. Additionally, the patient should be asked about their family history; patient should be asked for family members with the same symptoms, or history suggesting hereditary neuropathy.

Physical Examination

Evaluation of diabetic sensorimotor polyneuropathy includes a careful medical history and evaluation of either temperature or pinprick sensation to assess small-fiber, lower extremity reflexes, vibration sensation using a 128-Hz tuning fork and 10-g monofilament to assess large-fiber function. The 10-g monofilament test is also used to assess protective sensation. Assessment should start at the distal portions of the extremities (eg dorsal aspect of the hallux) on both sides, moving proximally until a sensory threshold is identified.

Diabetic Neuropathy_Initial Assesment 1

Screening

Early detection of diabetic polyneuropathy is important to prevent potentially severe complications such as amputation of infected, non-healing ulcers. The diagnosis of diabetic sensorimotor polyneuropathy is made clinically based on symptoms and the presence of symmetrical sensory loss or other typical signs. All patients with diabetes should be screened for DPN upon diagnosis of type 2 DM and 5 years after the diagnosis of type 1 DM, and at least yearly thereafter using simple clinical tests. Additionally, signs and symptoms of autonomic neuropathy must be evaluated in all patients at the time of diagnosis of type 2 DM and 5 years after the diagnosis of type 1 DM, and then at least annually.  

Screening Tests for Diabetic Autonomic Neuropathy  

Cardiovascular autonomic testing includes heart rate variability test during deep breathing and in response to standing up and the orthostatic test. Orthostatic hypotension is confirmed when the systolic blood pressure (SBP) falls ≥20 mmHg or diastolic BP falls ≥10 mmHg within 3 minutes of moving from a supine to an upright tilt table test or standing position. Other tests for diabetic autonomic neuropathy include sweat testing, urodynamic studies, gastric emptying tests, and endoscopy or colonoscopy. The measurement of gastric emptying with scintigraphy of digestible solids at 15-minute intervals for 4 hours after food intake is the gold standard diagnostic test for gastroparesis. An alternative test for gastroparesis is the C octanoic acid breath test.