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

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • New and Noteworthy
    • Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Special Collections
    • Recent ADA Position Statements
  • Info
    • About the Journal
    • Meet the Editors
    • Reprints & Permissions
    • Journal Policies
    • For Authors
    • For Reviewers
    • For Advertisers
  • Subscriptions
    • Manage Online Access
    • Individual Subscriptions
    • Institutional Subscriptions
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Diabetes Discovery
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • Standards of Medical Care
    • Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • New and Noteworthy
    • Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Special Collections
    • Recent ADA Position Statements
  • Info
    • About the Journal
    • Meet the Editors
    • Reprints & Permissions
    • Journal Policies
    • For Authors
    • For Reviewers
    • For Advertisers
  • Subscriptions
    • Manage Online Access
    • Individual Subscriptions
    • Institutional Subscriptions
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Diabetes Discovery
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • Peer Review
Special Article Collection: Insulin

Pharmacokinetics and Pharmacodynamics of Biosimilar Insulins: Is Clamp Technology Fit for Purpose?

  1. Philip Home⇑
  1. Institute for Cellular Medicine-Diabetes, Newcastle University, Newcastle upon Tyne, U.K.
  1. Corresponding author: Philip Home, philip.home{at}ncl.ac.uk.
Diabetes Care 2015 Dec; 38(12): 2234-2236. https://doi.org/10.2337/dc15-1046
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

Article Figures & Tables

Tables

  • Table 1

    Some glucose clamp advantages and limitations in the study of subcutaneous injection profiles of insulin preparations

    Advantages
     Ability to study PK and PD together and understand relationships
     Ability to study PK without possible disturbance of subcutaneous absorption by adrenergic hormone release through hypoglycemia
     Ability to study PD without disturbance of glucose dynamics from counterregulatory hormone changes or concentration-driven changes in glucose disposal (glucose uptake and urinary glucose disposal)
     Ability to study PD without disturbance of hepatic autoregulation of glucose production
    Disadvantages
     The technique requires research skills, in particular if conducted in people with type 1 diabetes.
     Insulin given to correct or maintain prior blood glucose control will continue to have measurable action for around 1.5 h.
     In type 1 diabetes, management of change from prior insulin (usually intravenous) can be problematic and interferes with interpretation of PK until about 0.5 h after this can be discontinued (unless a specific insulin assay is available) and with PD for about 1.5 h (due to half-time of insulin action).
     In type 1 diabetes, when loss of action of the studied insulin occurs at end of clamp, insulin must be given or glucose levels left to rise above clamp levels, both options interfering with interpretation of PD and the former with PK (unless a specific insulin assay is available).
     In people without diabetes and people with type 2 diabetes, clamp conduct must be good to prevent stimulation of endogenous insulin secretion.
     C-peptide measurements can be used to correct for gradual changes in endogenous insulin secretion, but the long plasma half-life of C-peptide (20 min) means this is problematic for studies of faster-acting insulins and that it cannot correct for rapid changes due to poor clamp technique, while in type 2 diabetes, proinsulin (which cross-reacts in many C-peptide assays) poses additional interpretation problems.
     PD (glucose infusion rate) estimation has higher variance than insulin concentration (PK) and, in particular, in type 1 diabetes often needs smoothing algorithms for determination of profiles.
     In studies of long-acting insulins, the metabolic state is increasingly that of fasting/starvation (glucose infusion rate is low), so the metabolic state changes with time (notably hepatic glucose output); the clamp level, if constant, deviates from physiological levels, and the glucose infusion rate is then artifactually disturbed.
     In studies of long-acting insulins, even with larger doses, plasma insulin levels at the beginning and end of the studies are around the LLoQ of the assay and indeed often so in some individuals for long periods: statistical handling of such undetectable levels can create very large changes and uncertainties in the shape of the published profile.
     In people with type 1 diabetes and people with type 2 diabetes exposed to insulin, insulin antibody–bound insulin will interfere with interpretation of insulin assays; the interference can be erratic and result in high variance of measured levels.
PreviousNext
Back to top
Diabetes Care: 38 (12)

In this Issue

December 2015, 38(12)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Masthead (PDF)
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

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

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.
Pharmacokinetics and Pharmacodynamics of Biosimilar Insulins: Is Clamp Technology Fit for Purpose?
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
Citation Tools
Pharmacokinetics and Pharmacodynamics of Biosimilar Insulins: Is Clamp Technology Fit for Purpose?
Philip Home
Diabetes Care Dec 2015, 38 (12) 2234-2236; DOI: 10.2337/dc15-1046

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

Pharmacokinetics and Pharmacodynamics of Biosimilar Insulins: Is Clamp Technology Fit for Purpose?
Philip Home
Diabetes Care Dec 2015, 38 (12) 2234-2236; DOI: 10.2337/dc15-1046
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
    • Article Information
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Insulin’s Role in Diabetes Management: After 90 Years, Still Considered the Essential “Black Dress”
  • Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents
  • Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection
Show more Special Article Collection: Insulin

Similar Articles

Navigate

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

 

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

© 2018 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.