Diabetic Neuropathy
GENERAL PRINCIPLES
Classification
Diabetic neuropathy can be classified as (1) subclinical neuropathy, determined by abnormalities in electrodiagnostic and quantitative sensory testing; (2) diffuse symmetrical polyneuropathy with distal symmetric sensorimotor losses ± autonomic syndromes; and (3) focal syndromes.33
Epidemiology
Distal symmetric polyneuropathy (DPN) is the most common neuropathy in developed countries and accounts for more hospitalizations than all the other diabetic complications combined.
Sensorimotor DPN is a major risk factor for foot trauma, ulceration, and Charcot arthropathy and is responsible for 50%- 75% of nontraumatic amputations.Prevention
• Sensation in the lower extremities should be documented at least annually, using a combination of modalities such as 10 g monofilament, tuning fork (frequency of 128 Hz) or pinprick, and temperature.
• Foot examination should be conducted at least annually to evaluate the presence of musculoskeletal deformities, skin changes, and pulses, in addition to the sensory examination.
TREATMENT
• Painful peripheral neuropathy responds variably to treatment with tricyclic antidepressants (e.g., amitriptyline 10-150 mg PO at bedtime), topical capsaicin (0.075% cream), or anticonvulsants (e.g., carbamazepine 100-400 mg PO bid, gabapentin 900-3600 mg/d, or pregabalin 150-300 mg/d). Patients should be warned about adverse effects, including sedation and anticholinergic symptoms (tricyclics), burning sensation (capsaicin), and blood dyscrasias (carbamazepine). #945;-Lipoic acid (600 mg bid) and high-dose thiamine (50-100 mg tid) have been tested in early DPN. Vitamin B12 should be checked and replaced if low.
• Orthostatic hypotension: Treatment is symptomatic and includes postural maneuvers, use of compressive garments (e.g., Jobst stockings), and intravascular expansion using sodium chloride 1-4 g PO qid and fludrocortisone 0.1-0.3 mg PO daily.
Causes of orthostatic hypotension (other than diabetic autonomic neuropathy) should be excluded.• Intractable nausea and vomiting may be manifestations of impaired GI motility from autonomic neuropathy. DKA should be ruled out when nausea and vomiting are acute and adrenal insufficiency should be excluded. Frequent, small meals (six to eight per day) of soft consistency that are low in fat and fiber provide intermittent relief. Parenteral nutrition may become necessary in refractory cases.
Pharmacologic therapy includes the prokinetic agent metoclopramide, 10-20 mg PO (or as a suppository) before meals and at bedtime, and erythromycin, 125-500 mg PO qid for short-term therapy. Extrapyramidal side effects (tremor and tardive dyskinesia) from the antidopaminergic actions of metoclopramide may limit therapy. Cyclical vomiting unrelated to a GI motility disorder appears to respond to amitriptyline 25-50 mg PO at bedtime.
• Diabetic cystopathy, or bladder dysfunction, results from impaired autonomic control of detrusor muscle and sphincteric function. Manifestations include urgency, dribbling, incomplete emptying, overflow incontinence, and urinary retention. Recurrent urinary tract infections are common in patients with residual urine. Treatment with bethanechol 10 mg tid or intermittent self-catheterization may be required to relieve retention.
• Chronic, persistent diarrhea in patients with diabetes is probably multifactorial. Celiac disease and inflammatory bowel diseases should be ruled out, particularly in patients with T1DM. Exocrine pancreatic dysfunction should be considered. Bacterial overgrowth has been considered as an etiology but is difficult to diagnose. Empiric treatment with broad-spectrum antibiotics (e.g., azithromycin, tetracycline, cephalosporins) along with metronidazole may be beneficial. Antifungal agents and probiotic replacement can be tried. If diarrhea persists, loperamide or octreotide 50-75 mg SC bid can be effective in patients with intractable diarrhea.