Elsevier

Clinical Therapeutics

Volume 40, Issue 6, June 2018, Pages 828-849
Clinical Therapeutics

Reviews
Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy

https://doi.org/10.1016/j.clinthera.2018.04.001Get rights and content

Abstract

Purpose

Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately half of patients with diabetes. DPN is symmetric and predominantly sensory, starting distally and gradually spreading proximally in a glove-and-stocking distribution. It causes substantial morbidity and is associated with increased mortality. The unrelenting nature of pain in this condition can negatively affect a patient's sleep, mood, and functionality and result in a poor quality of life. The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN.

Methods

A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. This review considers seminal and novel research in epidemiology; diagnosis, especially in relation to novel surrogate end points; and the treatment of neuropathic pain in DPN. We also consider potential new pharmacotherapies for painful DPN.

Findings

DPN is often misdiagnosed and inadequately treated. Other than improving glycemic control, there is no licensed pathogenetic treatment for diabetic neuropathy. Management of painful DPN remains challenging due to difficulties in personalizing therapy and ascertaining the best dosing strategy, choice of initial pharmacotherapy, consideration of combination therapy, and deciding on defining treatment for poor analgesic responders. Duloxetine and pregabalin remain first-line therapy for neuropathic pain in DPN in all 5 of the major published guidelines by the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, National Institute of Clinical Excellence (United Kingdom), and the American Diabetes Association, and their use has been approved by the US Food and Drug Administration.

Implications

Clinical recognition of DPN is imperative for allowing timely symptom management to reduce the morbidity associated with this condition.

Introduction

Diabetes has reached epidemic proportions worldwide, with International Diabetes Federation estimates suggesting a prevalence of 425 million people worldwide in 2017, rising to 628 million by 2045.1 This rise will be accompanied by an increase in the prevalence of the complications of diabetes.2 DPN is the most common cause of neuropathy worldwide, and is estimated to affect around half of people with diabetes.3, 4 It causes considerable morbidity, impairs quality of life, and increases mortality.5, 6 Indeed, approximately one fourth of the US health care expenditure on diabetes is spent on DPN.7

Diabetic neuropathy refers to a collection of clinically diverse disorders affecting the nervous system, with differing anatomic features, clinical courses, and phenotypes. The common underlying pathophysiology is a consequence of hyperglycemia and microangiopathy.8 The commonest form is distal symmetric sensorimotor polyneuropathy9; however, most body systems can be affected through involvement of the autonomic nerves. Despite the considerable, health care–related economic burden and effect on quality of life in DPN, treatment options are limited and prevention remains the key goal.10 The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN.

Section snippets

Materials and Methods

A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. Articles published from inception of databases to December 2017 were identified. Data from articles that were felt not relevant by authors with the guidance of the senior reviewers (R.A.M., U.A.) were excluded from the review.

Results

Databases searches were undertaken and 188 papers were cited in the final manuscript. Authors excluded studies that were not considered relevant to the aims of this article. Further appraisal of selected articles were undertaken and any relevant explanatory data from said articles were included in the present review as descriptive prose.

Conclusions

DPN is common, often misdiagnosed, and inadequately treated. DPN accounts for considerable morbidity and mortality and reduced quality of life. Clinical recognition is required for allowing timely symptomatic management to reduce the morbidity associated with this condition. Glycemic control is the central component of treatment, but it is difficult to achieve for many patients. Cardiovascular risk factors play a major role in the pathogenesis of DPN and should be intensively controlled with a

Conflicts of Interest

The authors have indicated that they have no conflicts of interest with regard to the content of this article.

Acknowledgments

No other individuals were involved in the production of this manuscript. There was no financial support for the production of this article. All authors contributed equally to the production of this manuscript.

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