Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Perspective in Diabetes

Clinical Trials of Diabetic Neuropathy: Past, Present, and Future

  1. Michael A Pfeifer and
  2. Mary P Schumer
  1. Department of Internal Medicine, Division of Metabolism, Endocrinology, Nutrition and Diabetes, Diabetes Research and Treatment Center at Southern Illinois University, Southern Illinois University School of Medicine Springfield, Illinois
  1. Address correspondence and reprint requests to Dr. Michael A. Pfeifer, Diabetes Research and Treatment Center at SIU, Southern Illinois University School of Medicine, P.O. Box 19230, Mail Stop 1619, Springfield, IL 62794–1619.
Diabetes 1995 Dec; 44(12): 1355-1361. https://doi.org/10.2337/diab.44.12.1355
PreviousNext
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

This article reviews current knowledge of the etiology of diabetic neuropathy and the outcomes and limitations of previous trials and discusses future directions for the investigation of its prevention and treatment. Proposed mechanisms for the development of diabetic neuropathy have been widely studied. It has been shown that there is improvement of nerve function associated with some short-term clinical trials of treatments that address a number of possible etiologic pathways. Improvement of morphometry has also been demonstrated in some short-term clinical trials. However, with the exception of the Diabetes Control and Complications Trial (DCCT), long-term trials with adequate statistical power to evaluate clinical outcome endpoints have not been conducted. The changes in nerve function are similar in most of the clinical trials. For instance, in four clinical trials directed at separate mechanisms (improved glucose control, high myo-inositol diet, therapy with an aldose reductase inhibitor, and therapy with supplementary γ-linolenic acid), a similar improvement in peroneal motor velocity of 1–2 m/s is observed. This implies that each of the proposed mechanisms contributes equally to the development of neuropathy or that there is some redundancy to their mechanisms. In addition to an etiologic approach, nonspecific neural stimulants, such as gangliosides and nerve growth factors, have also been investigated for the treatment of diabetic neuropathy. With the exception of the prevention of neuropathy by intensive glycemic control, the modest improvements with all other treatments have not led to sufficient evidence to approve any approach. Subanalyses of previous clinical trials suggest that treatment effects are greatest and most clear in patients with mild-to-moderate early neuropathy (stage I or early stage II). Thus, variation in composition and severity of baseline neuropathic disease inpast clinical trials may have “washed out” any potential treatment effect. It is encouraging that more recent clinical trials have established more rigid inclusion and exclusion criteria so as to recruit only those patients with early or mild-to-moderate disease and a more homogeneous study population. Improvement with treatment has been measured with several markers including nerve conduction velocity, quantitative sensory testing, autonomic function testing, and morphometric changes. Presumably, the combined finding of improved nerve function and improved nerve morphometry will predict improvement in long-term clinical outcomes such as impaired sensation, painful neuropathy, insensitive feet, neurotrophic ulceration, and/or amputation. However, data to support this possibility are still lacking. It is our opinion that the overall design of neuropathy trials must consider present knowledge about complications in general and neuropathy specifically. We recommend that future trials be conducted over long periods with clinically significant outcomes as in the angiotensin-converting enzyme-inhibitor nephropathy trials and the DCCT with the recognition that reducing the development, rather than reversal, of complications is the best thatcan be reasonably expected. Patients with mild-to-moderate neuropathy (stage I or early stage II) with presumably more metabolic than structural neuropathy would be preferred subjects, and follow-up of 3–5 years is likely to be needed.

  • Received February 27, 1995.
  • Revision received September 14, 1995.
  • Accepted September 14, 1995.
  • Copyright © 1995 by the American Diabetes Association

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this Issue

December 1995, 44(12)
  • Table of Contents
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Clinical Trials of Diabetic Neuropathy: Past, Present, and Future
(Your Name) has forwarded a page to you from Diabetes
(Your Name) thought you would like to see this page from the Diabetes web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Clinical Trials of Diabetic Neuropathy: Past, Present, and Future
Michael A Pfeifer, Mary P Schumer
Diabetes Dec 1995, 44 (12) 1355-1361; DOI: 10.2337/diab.44.12.1355

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Clinical Trials of Diabetic Neuropathy: Past, Present, and Future
Michael A Pfeifer, Mary P Schumer
Diabetes Dec 1995, 44 (12) 1355-1361; DOI: 10.2337/diab.44.12.1355
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Redox Paradox
  • Dissipating Excess Energy Stored in the Liver Is a Potential Treatment Strategy for Diabetes Associated With Obesity
  • Identification of Individuals With Insulin Resistance Using Routine Clinical Measurements
Show more Perspective in Diabetes

Similar Articles

Navigate

  • Current Issue
  • Online Ahead of Print
  • Scientific Sessions Abstracts
  • Collections
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes Care
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.