arrow Log In to View Account     |      
Johns Hopkins Medicine
Hopkins Logo

Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Diabetic Microvascular Complications: Are We Doing Enough?
Part II: Diabetic Peripheral Neuropathy

To delineate the multifactorial pathogenesis of diabetic microvascular complications, review methods of diagnosis, and present emerging data on future treatment options.

This activity is designed for neurologists, endocrinologists, diabetologists, and primary care physicians. No prerequisites required.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Discuss the impact and prevalence of diabetic microvascular complications, including retinopathy, nephropathy, and peripheral neuropathy.
  • Review the multifactorial pathogenesis of microvascular damage.
  • Discuss the importance of screening and early diagnosis of diabetic peripheral neuropathy to prevent complications.
  • Evaluate the current and emerging screening and diagnostic tools for peripheral neuropathy.
  • Evaluate emerging data on future treatment options to treat the underlying process of microvascular damage.

The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.

Release date: September 15, 2004. Expiration date: September 15, 2006.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Eli Lilly and Company.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:


Christopher D. Saudek, MD
Hugh P. McCormick Family Professor of Endocrinology and Metabolism
The Johns Hopkins University School of Medicine
Director, Johns Hopkins Diabetes Center
Program Director,
General Research Center at Johns Hopkins
Baltimore, Maryland
Dr Saudek reports serving as a consultant to Eli Lilly and Company.


Andrew J. M. Boulton, MD, DSc, FRCP
Professor of Medicine
University of Manchester
Consultant Physician
Manchester Royal Infirmary
Manchester, United Kingdom
Professor of Medicine
Division of Endocrinology
University of Miami
Miami, Florida
Dr Boulton reports serving as a consultant to and receiving honoraria from Eli Lilly and Company.

Vera Bril, BSCI, MD, FRCPC
Professor of Medicine
Department of Neurology
University Health Network
Toronto General Hospital
University of Toronto
Toronto, Ontario, Canada
Dr Bril reports having no significant financial or advisory relationships with corporate organizations related to this activity.

David R. Cornblath, MD
Professor of Neurology
The Johns Hopkins University School of Medicine
Director, Neurology EMG Laboratory
The Johns Hopkins Hospital
Baltimore, Maryland
Dr Cornblath reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Eva L. Feldman, MD, PhD
Professor of Neurology
Department of Neurology
University of Michigan Health System
Ann Arbor, Michigan
Dr Feldman reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Andrea Vincent, PhD
Research Investigator
Department of Neurology
University of Michigan Health System
Ann Arbor, Michigan
Dr Vincent reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Notice: In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:

Dr Bril—a-lipoic acid, aminoguanidine, AS-3201, bupropion, capsaicin cream, duloxetine, fidarestat, gabapentin, isosorbide dinitrate spray, lamotrigine, memantine, oxcarbazepine, oxycodone, pregabalin, ruboxistaurin, topiramate, tramadol, venlafaxine, zenarestat, zonisamide.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

The Diagnosis, Prevention, And Treatment Of Diabetic Peripheral Neuropathy: A Comprehensive Overview
Christopher D. Saudek, MD*

Diabetic neuropathy is the most common microvascular complication associated with diabetes and the most common form of diabetic neuropathy is sensorimotor diabetic peripheral neuropathy (DPN). As many as 50% of all patients with diabetes have DPN. The personal suffering is great, and the financial cost to society is also considerable, particularly since DPN is a major risk factor for lower extremity amputation. An estimated 15% of all individuals with diabetes requiring an amputation over the course of their lifetime.

We have known for some years that the severity of DPN correlates with the duration of diabetes, the patient's level of glycemic control, smoking, excess alcohol intake, and the age of the patient. We know that DPN affects the longest nerves first, progressing proximally. Thus, individuals with DPN usually experience dysaesthesias or loss of distal sensation in the feet, although DPN may occasionally present with symptoms in the hands. Most often, DPN progresses from discomfort toward numbness. Unfortunately, while lack of pain may be considered a blessing, it is the insensate foot that, by unrecognized trauma, can develop ulcers and infections, ultimately being at highest risk of amputation.

Patients with established DPN who do not receive proper foot care may develop nonhealing infections and foot ulcerations. Therefore, close attention must be paid to prevention of foot ulcers as well as slowing the progression of DPN. But treatment options for symptom control and prevention are relatively limited. Even careful glycemic control may not prevent the progression of DPN, since some patients appear exquisitely sensitive to even the mildest levels of hyperglycemia. One new insight, for example, is that DPN may develop when diabetes is not even present, ie in the "prediabetic" states of impaired glucose tolerance or impaired fasting glucose.

The good news is that our learning curve now is particularly steep. Many new insights are emerging about DPN. Our understanding of the basic pathophysiology of DPN is evolving rapidly. The importance of oxidative stress, a unifying hypothesis for many diabetic complications, is discussed in some detail in this monograph. And based on this hypothesis, there are new drugs being developed that hold promise of addressing the underlying cause of DPN. Clinical trial results provide new hope to patients who suffer from DPN.

In this issue of Advanced Studies in Medicine, Dr Andrew J. M. Boulton, in a clinician interview, discusses the importance of screening and diagnosing DPN early. He offers his insights into which patients should be screened for DPN, which clinical indicators healthcare providers might use for DPN, and how often to screen for DPN.

The interview is followed by 3 review articles. The first, by Drs Eva Feldman and Andrea Vincent, presents the current medical understanding on the multifactorial pathogenesis of DPN. The article includes describes for the clinician the 4 major pathways of glucose metabolism implicated in the development of DPN and discusses the possibility that glucose-mediated cellular oxidative stress may be the unifying mechanism underlying the metabolic and vascular dysfunction seen in DPN.

Dr David Cornblath explores the finer points of the detection and diagnosis of DPN, reviewing the methods and tools used to objectify DPN. Given the variability of symptoms and the subjectivity of many clinical assessment tools, it is particularly important to know about available gold-standard tests. While certain routine clinical assessments are useful in the office, better tests are available for use in clinical trials designed to test benefit objectively.

Finally, Dr Vera Bril reviews current and emerging treatments that target the symptoms of diabetic neuropathy, and also presents the emerging data on new therapies that make use of current understanding of pathogenesis.

Drs Cornblath and Bril both contribute a case study that illustrates some of the important elements, methodologies, and tools of screening and diagnosis of DPN, in addition to exploring the use of pharmacotherapy.

In sum, painful and limb-threatening foot problems are not an inevitable consequence of diabetes or DPN. But physicians, podiatrists, therapists, educators, and patients need to work together to reduce the morbidity and amputation rate of DPN. Developing strategies for early identification of those at potential risk for DPN is an important component in preventing or slowing the development of diabetic microvascular complications. Simple interventions can reduce amputations by up to 80%. But further research is essential, since our tools are limited. With a better understanding of the pathogenesis of DPN and the emergence of new treatments, we are entering an era that could allow prevention and even the possibility of reversing DPN. This monograph will bring you up to date on the latest developments.

*Hugh P. McCormick Family Professor of Endocrinology and Metabolism; The Johns Hopkins University School of Medicine; Director, The Johns Hopkins Diabetes Center; Program Director, General Research Center at Johns Hopkins, Baltimore, Maryland.

Address correspondence to: Christopher D. Saudek, MD, Johns Hopkins University School of Medicine, Osler 576, 600 North Wolfe St, Baltimore, MD 21287. E-mail:

Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by ASiM CE, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2017 by ASiM CE, LLC. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of ASiM CE LLC.