Diabetic Neuropathy: An Intensive Review

Jeremiah John Duby; R. Keith Campbell; Stephen M. Setter; John Raymond White; Kristin A. Rasmussen

Abstract and Introduction

Abstract

Purpose: The epidemiology, classification, pathology, and treatment of diabetic neuropathy are reviewed.
Summary: Diabetic peripheral neuropathy is a common complication of diabetes that can cause significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetes patients have peripheral neuropathy; the annual incidence rate is approximately 2%. The primary risk factor is hyperglycemia. Sensorimotor neuropathy is marked by pain, paresthesia, and sensory loss. Cardiac autonomic neuropathy (CAN) may contribute to myocardial infarction, malignant arrhythmia, and sudden death. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy. Genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder. The pathology of diabetic neuropathy involves oxidative stress, advanced glycation end products, polyol pathway flux, and protein kinase C activation; all contribute to microvascular disease and nerve dysfunction. For symptom management current evidence from clinical trials supports the use of desipramine, amitriptyline, capsaicin, tramadol, gabapentin, bupropion, and venlafaxine as preferred medications. Citalopram, nonsteroidal antiinflammatory drugs, and opioid analgesics may be used as adjuvant agents. Lamotrigine, oxcarbazepine, paroxetine, levodopa, and α-lipoic acid are alternative considerations. Evidence supporting the use of zonisamide, fluoxetine, mexiletine, dextromethorphan, and phenytoin is considered equivocal. Complementary therapies have also shown efficacy. The symptoms of CAN may be ameliorated with fludrocortisone, clonidine, midodrine, dihydroergotamine or caffeine, octreotide, and β-blockers. Gastroparesis may be treated with metoclopramide or erythromycin. The most promising disease-modifying therapy is ruboxistaurin, which is in Phase III trials. Glycemic control remains the foundation of prevention and the prerequisite of adequate treatment.
Conclusion: Diabetic neuropathy is a many-faceted complication of diabetes that can be managed symptomatically with an array of drugs.Introduction

Diabetic peripheral neuropathy is a common complication of diabetes that can affect virtually every tissue of the body and cause significant morbidity and mortality. Current understanding of the pathophysiology is complicated and incomplete, but basic experimental research is on the threshold of producing the first disease-modifying therapies. The available treatments are modestly to moderately effective in relieving symptoms but are limited by adverse effects and drug interactions. The emphasis of management of diabetic neuropathy remains prevention by glycemic control. The purpose of this article is to review the epidemiology, classification, pathology, and treatment of diabetic neuropathy.

Section 1 of 6 Jeremiah John Duby, Pharm.D., is General Practice Resident, University of Arizona, Tucson. R. Keith Campbell, B.Pharm., M.B.A., CDE, FASHP, FAPhA, is Professor; Stephen M. Setter, Pharm.D., D.V.M., is Assistant Professor; and John Raymond White is Associate Professor of Pharmacotherapy, Department of Pharmacotherapy, College of Pharmacy, Washington State University (WSU), Spokane. Kristin A. Rasmussen is a D.V.M. degree candidate, College of Veterinary Medicine, WSU.
Am J Health-Syst Pharm 61(2):160-176, 2004. © 2004 American Society of Health-System Pharmacists
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