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

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • 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
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • 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
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Letters: Observations

Comparative Trial Between Insulin Glargine and NPH Insulin in Children and Adolescents With Type 1 Diabetes

  1. Edith Schober, MD1,
  2. Eugen Schoenle, MD2,
  3. Jacobus Van Dyk, MD3,
  4. Karin Wernicke-Panten, MD4 and
  5. the Pediatric Study Group of Insulin Glargine
  1. 1University Children’s Hospital, Vienna, Austria
  2. 2University Children’s Hospital, Zurich, Switzerland
  3. 3University of Pretoria, Pretoria Academic Hospital, Pretoria, South Africa
  4. 4Clinical Development, Aventis Pharma Deutschland, Frankfurt, Germany
    Diabetes Care 2001 Nov; 24(11): 2005-2006. https://doi.org/10.2337/diacare.24.11.2005
    PreviousNext
    • Article
    • Info & Metrics
    • PDF
    Loading

    Studies such as the Diabetes Control and Complications Trial have shown that, as in adult patients, intensive diabetes management in adolescent patients results in better glycemic control and delays the onset and slows the progression of vascular and neurological complications (1). However, a cross-sectional multinational study showed that less than one-third of the children and adolescents who underwent treatment for diabetes had adequate metabolic control (2). Providing a constant supply of basal insulin that mimics that of healthy individuals is an essential aspect of maintaining tight glycemic control in patients with type 1 diabetes. The traditional NPH insulin and ultralente basal insulin formulations do not provide a constant and reliable 24-h basal insulin supply because their duration of action is too short, and unwanted peaks of action in the night can cause nocturnal hypoglycemia (3). This is of particular relevance in children and adolescents, who are more prone to hypoglycemic episodes (4,5).

    A new long-acting insulin analog has been developed using recombinant DNA technology. Insulin glargine differs from human insulin by the addition of two additional arginines on the COOH terminus of the B-chain and the replacement of an asparagine residue with glycine on the A-chain (6). The resulting molecule has a peakless, prolonged time-action profile and can be used once daily. These features enable insulin glargine to provide sufficient basal insulin over 24 h when used in a basal-bolus regimen while limiting the incidence of hypoglycemic, particularly nocturnal hypoglycemic, episodes (7). The objective of this study was to compare the metabolic effect and safety of insulin glargine with NPH insulin in children and adolescents with type 1 diabetes.

    In a multicenter open-label randomized study, 349 patients with type 1 diabetes, aged 5–16 years, who were using at least three daily preprandial injections of normal insulin and who had an HbA1c value of <12%, were treated for 6 months. Patients received insulin glargine once daily (at bedtime), irrespective of their prior regimen (174 patients), whereas the regimen for patients receiving NPH insulin was either once (at bedtime in 114 patients) or twice daily (in the morning and at bedtime in 61 patients), based on their prior treatment regimen. Titration of the bedtime dose of insulin was related to fasting blood glucose (FBG), with a target of 4.4–8.8 mmol/l. Regular insulin was injected before meals according to the habits of the patients. Insulin glargine and NPH insulin treatment groups had a similar distribution in terms of sex, age (11.8 ± 2 vs. 11.5 ± 2 years), BMI (18.8 ± 2 vs. 18.9 ± 2 kg/m2), ethnic group, puberty stage (preadolescent 32.8 vs. 35.4%; and adolescent 67.2 vs. 64.6%), and age at onset of diabetes (7.4 ± 3.17 vs. 7.4 ± 3.31 years).

    The primary efficacy measure was mean change from baseline in GHb levels, which was determined by analysis of covariance (ANCOVA). The difference in mean change from baseline between insulin glargine and NPH insulin was estimated using adjusted means together with the associated SE and 95% CI from the ANCOVA model. The secondary efficacy measures were mean change in FBG levels from baseline (analyzed by ANCOVA) and incidence of hypoglycemia (compared between treatment groups using rank analysis of variance). Hypoglycemia was catergorized as either symptomatic (with clinical symptoms that could be confirmed by blood glucose levels <2.8 mmol/l) or asymptomatic (any event with a confirmed blood glucose level <2.8 mmol/l but without any symptoms). Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required assistance from another person and which was associated with a blood glucose level <2.8 mmol/l or prompt recovery after oral carbohydrate or intravenous glucose or glucagon administration (8).

    There was no difference between insulin glargine and NPH insulin in terms of change in GHb from baseline to end point (0.28 ± 0.09% vs. 0.27 ± 0.09%, P = 0.93). However, FBG decreased more from baseline to end point in the insulin glargine group (−1.29 mmol/l) than in the NPH insulin group (−0.68 mmol/l; P = 0.02). At end point, a higher percentage of insulin glargine–treated patients (43.9%) than NPH insulin–treated patients (39.0%) reached the target range of 4.4–8.8 mmol/l. These improved FBG levels could be due to the extended time-action profile of insulin glargine.

    During the entire study period, the percentage of subjects reporting at least one episode of symptomatic hypoglycemia was similar for insulin glargine and NPH insulin treatment (78.9 and 79.3%, respectively); however, fewer patients in the insulin glargine versus the NPH insulin group reported severe hypoglycemia (23.0 vs. 28.6%, respectively; P = 0.22, Cochran-Mantel-Haenszel test) and severe nocturnal hypoglycemia (12.6 vs. 17.7%, respectively; P = 0.19), although these differences were not statistically significant.

    Both insulin glargine and NPH insulin treatments were well tolerated. Of note, injection site reactions, categorized as adverse events of special interest, were evenly distributed between the insulin glargine and NPH insulin groups (9.2 vs. 8.6%, respectively). Serious adverse events were observed more often in the NPH insulin group than in the insulin glargine group (13.7 vs. 5.8%, respectively; P < 0.02, Fisher’s exact test).

    In conclusion, a once-daily subcutaneous dose of insulin glargine provides glycemic control that is at least as effective as once- or twice-daily NPH insulin in children and adolescents with type 1 diabetes, with significantly lower FBG levels and a trend toward fewer episodes of severe hypoglycemia and nocturnal hypoglycemia.

    Appendix

    Investigators for the Pediatric Study Group of Insulin Glargine

    Austria: Peter Kitzler, MD; Klaus Schmitt, MD; Edith Schober, MD; Belgium: Jean De Schepper, MD; Raoul Rooman, MD; Croatia: Katarina Cvijovic, MD; Czech Republic: Stanislava Kolouskova, MD, Jan Lebel, MD; Libuse Osickova, MD; Jaroslav Skvor, MD; Jirina Venhacova, MD; Finland: Marja-Liisa Kaar, MD; Paevi Tapanainen, MD; Raisa Lounamaa, MD; Matti Salo, MD; Germany: Juergen Herwig, MD; Eberhard Kauf, MD; Andreas Lemmer, MD; Ulf Wendel, MD; Bernd Schulze-Schleppinghoff, MD; South Africa: Larry Distiller, MD; L. Robertson, MD; J. Van Dyk, MD; Switzerland: Eugen Schoenle, MD; the Netherlands: Mieke Houdijk, MD; Joan Schermer-Rotte, MD; Adrianus van Rhijn, MD; U.K.: David Dunger, MD.

    Footnotes

    • Address correspondence to Edith Schober, University Children’s Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: edith.schober{at}akh-wien.ac.at.

      E.S. received supporting funds from Aventis Pharma. J.V.D. was paid consultation fees by Aventis for each participating patient. K.W.-P. holds stock in Aventis Pharma Germany.

    References

    1. ↵
      Diabetes Control and Complications Trial Research Group: Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 125:177–188, 1994
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      Mortensen HB, Hougaard P, the Hvidore Study Group on Childhood Diabetes: Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. Diabetes Care 20:714–720, 1997
      OpenUrlAbstract/FREE Full Text
    3. ↵
      Heinemann L, Richter B: Clinical pharmacology of human insulin. Diabetes Care 16(Suppl. 3):S90–S100, 1993
      OpenUrl
    4. ↵
      Bhatia V, Wolfsdorf J: Severe hypoglycemia in youth with insulin-dependent diabetes mellitus: frequency and causative factors. Pediatrics 88:1187–1193, 1991
      OpenUrlAbstract/FREE Full Text
    5. ↵
      Limbert C, Schwingshandl J, Haas J, Roth R, Borkenstein M: Severe hypoglycemia in children and adolescents with IDDM: frequency and associated factors. J Diabetes Complications 7:216–220, 1993
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedalk M, Heise T: Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 23:644–649, 2000
      OpenUrlAbstract/FREE Full Text
    7. ↵
      Matthews D, Pfeiffer C: A new long-acting insulin (HOE901) demonstrates less nocturnal hypoglycaemia when compared with protamine insulin in a clinical trial (Abstract). Diabetologia 41:A245, 1998
      OpenUrlCrossRef
    8. ↵
      The Diabetes Control and Complications Trial Research Group: Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 90:450–459, 1991
      OpenUrlCrossRefPubMedWeb of Science
    PreviousNext
    Back to top
    Diabetes Care: 24 (11)

    In this Issue

    November 2001, 24(11)
    • Table of Contents
    • About the Cover
    • Index by Author
    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.
    Comparative Trial Between Insulin Glargine and NPH Insulin in Children and Adolescents With Type 1 Diabetes
    (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.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Citation Tools
    Comparative Trial Between Insulin Glargine and NPH Insulin in Children and Adolescents With Type 1 Diabetes
    Edith Schober, Eugen Schoenle, Jacobus Van Dyk, Karin Wernicke-Panten
    Diabetes Care Nov 2001, 24 (11) 2005-2006; DOI: 10.2337/diacare.24.11.2005

    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

    Comparative Trial Between Insulin Glargine and NPH Insulin in Children and Adolescents With Type 1 Diabetes
    Edith Schober, Eugen Schoenle, Jacobus Van Dyk, Karin Wernicke-Panten
    Diabetes Care Nov 2001, 24 (11) 2005-2006; DOI: 10.2337/diacare.24.11.2005
    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
      • Appendix
      • Footnotes
      • References
    • Info & Metrics
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • Weight Gain and Gestational Diabetes Mellitus Is a Sensitive Issue
    • Beneficial Effects of a 4-Week Exercise Program on Plasma Concentrations of Adhesion Molecules
    • Malignant Melanoma Misdiagnosed as a Diabetic Foot Ulcer
    Show more Letters: Observations

    Similar Articles

    Navigate

    • Current Issue
    • Standards of Care Guidelines
    • 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
    • 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 Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.