Diabetic Autonomic Neuropathy

Aaron I. Vinik, MD, PhD.; Roy Freeman, MB, ChB.; Tomris Erbas, MD


Semin Neurol. 2003;23(4) 

In This Article

Treatment of Diabetic Autonomic Neuropathy

Treatment of Cardiac Autonomic Neuropathy and Orthostatic Hypotension

The results from the Diabetes Control and Complications Trial show that intensive glycemic treatment can prevent the development of abnormal heart rate variability and slow the deterioration of autonomic dysfunction over time for individuals with type 1 diabetes.[46] In a study of type 2 diabetic patients with microalbuminuria, the stepwise implementation of intensified multifactorial treatment slowed the progression to autonomic neuropathy.[47] Early identification of cardiovascular autonomic neuropathy permits timely initiation of therapy with the antioxidant α-lipoic acid, which appears to slow or reverse progression of neuropathies in some studies.[48] Beta-blockers that are cardioselective or lipophilic might modulate the effects of autonomic dysfunction in diabetes either centrally or peripherally by opposing the sympathetic stimulus, and thereby restore the parasympathetic-sympathetic balance.[49] Studies using angiotensin-converting enzyme inhibitors as a means to improve heart rate variability have resulted in conflicting results. Whereas quinapril significantly increased parasympathetic activity after 3 months of treatment, cardiovascular autonomic function did not change significantly after 12 months of treatment with trandolapril.[50,51]

The removal of potential reversible causes of orthostatic hypotension is the first and most important management step; 9-α-fluorohydrocortisone, a synthetic mineralocorticoid, is the medication of first choice for most patients with orthostatic hypotension.[4] Treatment is initiated with a 0.1 mg tablet and can be increased to 0.5 mg daily, although such high doses are usually not necessary. Unfortunately, this agent does not improve symptoms until fluid retention or edema develops. There is an associated risk of hypokalemia, hypertension particularly in the supine position, and, more rarely, congestive heart failure. A sympathomimetic agent can be added to fludrocortisone acetate should the patient remain symptomatic. The peripherally acting selective α-agonist midodrine is the most widely used of these pressors. Patient sensitivity to this agent varies and the dose should be titrated from 2.5 mg to 10 mg three times a day.

Treatment of Gastrointestinal Autonomic Neuropathy

Initial treatment of diabetic gastroparesis should focus on blood glucose control, which improves gastric motor dysfunction. In addition, patients should be advised to eat multiple small meals (four to six per day) and to reduce the fat content of their diet. They should also restrict their fiber intake to prevent the formation of bezoars. Prokinetic agents used to treat diabetic gastropathy are metoclopramide, domperidone, erythromycin, and levosulpiride.[39] Given in a dose of 10 mg orally 30 minutes before meals and at bedtime, metoclopramide accelerates gastric emptying and has a central antiemetic action. It also may release acetylcholine from intramural cholinergic neurons or directly stimulate antral muscle. Domperidone (10 to 20 mg four times a day), a peripheral D2 receptor antidopaminergic agent, is frequently helpful in the treatment of this disorder. Erythromycin and related macrolide compounds have motilin agonist properties. Intravenous and oral erythromycin (250 mg three times a day) improve gastric-emptying time in diabetic patients with gastroparesis.[52,53] The majority of patients can be treated with these medical interventions and jejunostomy tube placement is rarely necessary. Severe cases with intractable vomiting may benefit from nasogastric suctioning.

The severe and intermittent nature of diabetic diarrhea makes treatment and assessment difficult. Because afferent denervation may contribute to the problem, a bowel program that includes restriction of soluble fiber and regular effort to move the bowels is indicated. In addition, trials of gluten-free diet, restriction of lactose, cholestyramine, clonidine, somatostatin analog, pancreatic enzyme supplements, and antibiotics such as metronidazole may be indicated.[1]

Treatment of Genitourinary Autonomic Neuropathy

Once diagnosed, treatment may include withdrawal from offending medications coupled with psychological counseling, medical treatment, or surgery.[42] Medical treatment may include sildenafil taken at a dose of 50 mg. Sildenafil is a guanine monophosphate type-5 phosphodiesterase inhibitor that enhances blood flow to the corpora cavernosae with sexual stimulation. A lower dosage is needed for individuals with renal failure or liver dysfunction. Sildenafil should not be taken by individuals with unstable ischemic heart disease or those using nitroglycerin or other nitrate-containing medications.[39] Tadalafil (20 mg) and vardenafil (20 mg) are also effective in more than 60% of diabetic patients with erectile dysfunction. Other therapies include the injection of vasoactive substances such papaverine, phentolamine, and prostaglandin E1 into the corpus cavernosum, transurethral delivery of vasoactive agents, and the use of mechanical devices such as the vacuum erection device or constricting rings. Penile prosthetic implants may be used if these therapies fail or are not tolerated by the patient.

Patients with neurogenic bladder should be instructed to palpate their bladder and, if they are unable to initiate micturition when their bladders are full, use Crede's maneuver to start the flow of urine every 4 hours. Parasympathomimetics such as bethanechol (10 to 30 mg three times a day) are sometimes helpful, although frequently they do not help to fully empty the bladder. Extended sphincter relaxation can be achieved with a α1-blocker, such as doxazosin. Clean intermittent self-catheterization may also be used to facility emptying.

Treatment of Hyperhidrosis

This socially embarrassing phenomenon may be treated with anticholinergic agents such as trihexyphenidyl, propantheline, or scopolamine. High doses of these agents are usually required and therapy is usually limited by other anticholinergic side effects, such as dry mouth, urinary retention, and constipation. Glycopyrrolate may benefit diabetic patients with gustatory sweating.[54] In addition, local intracutaneous injection of botulinum toxin type A may be used to treat this disorder.[55]


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