HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lindholm, A. Articles by Råstam, J. Search for Related Content PubMed PubMed Citation Articles by Lindholm, A. Articles by Råstam, J. Social Bookmarking                What's this?

Immune Responses to Insulin Aspart and Biphasic Insulin Aspart in People With Type 1 and Type 2 Diabetes

¹ Novo Nordisk, Bagsvaerd, Denmark
² University of Newcastle Upon Tyne, Newcastle Upon Tyne, U.K.
³ University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
⁴ Division of Endocrinology and Diabetes, Ulm University, Ulm, Germany

OBJECTIVE—The antibody responses to a novel rapid-acting insulin analog, insulin aspart (IAsp), and their potential clinical correlates were studied with a specifically developed method in 2,420 people with diabetes treated for up to 1 year with preprandial subcutaneous injections of IAsp.

RESEARCH DESIGN AND METHODS—Circulating insulin antibodies were analyzed by radioimmunoassay with ¹²⁵I insulin or IAsp tracers and polyethylene glycol precipitation. Four multinational, open, parallel group studies were conducted in Europe and North America, with a total of 1,534 people with diabetes exposed to IAsp and 886 people exposed to human insulin (HI) as meal-related insulin for 6–12 months.

RESULTS—Insulin antibodies specific to HI or IAsp were absent in a majority of patients throughout the 6- to 12-month study periods. A majority of the patients (64–68%) had antibodies cross-reacting between HI and IAsp when entering the studies, with baseline levels (means ± SD of percent bound/total) of 16.6 ± 16.3% in study 1 and 10.3 ± 14.0% in study 4. In all four studies, cross-reactive antibodies increased in patients exposed to IAsp, with a maximum at 3 months, and thereafter there was a decline toward baseline levels at 9–12 months (levels at 3 and 12 months: 22.3 ± 19.7 and 16.8 ± 16.5% in study 1 and 21.5 ± 21.9 and 16.9 ± 17.4% in study 4). Antibody levels showed similar changes in people with type 1 and type 2 diabetes, and there was no consistent relationship between antibody formation and glycemic control or between antibody formation and safety in terms of adverse events.

CONCLUSIONS—Treatment with IAsp is associated with an increase in cross-reactive insulin antibodies, with a subsequent fall toward baseline values, without any indication of clinical relevance because no effect on efficacy or safety could be identified.

Abbreviations: BIAsp, biphasic insulin aspart • BHI, biphasic human insulin • B/T, bound/total • C_max, maximum glucose concentration • HI, human insulin • IAsp, insulin aspart • PEG, polyethylene glycol • t_max, time of maximum concentration.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. E. Fineberg, T. T. Kawabata, D. Finco-Kent, R. J. Fountaine, G. L. Finch, and A. S. Krasner Immunological Responses to Exogenous Insulin Endocr. Rev., October 1, 2007; 28(6): 625 - 652. [Abstract] [Full Text] [PDF]

				J-W Chen, J Frystyk, T Lauritzen, and J S Christiansen Impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week treatment with multiple daily injections of biphasic insulin aspart 30 in patients with type 1 diabetes Eur. J. Endocrinol., December 1, 2005; 153(6): 907 - 913. [Abstract] [Full Text] [PDF]

				S. Madsbad, O. Schmitz, J. Ranstam, G. Jakobsen, and D. R. Matthews Improved Glycemic Control With No Weight Increase in Patients With Type 2 Diabetes After Once-Daily Treatment With the Long-Acting Glucagon-Like Peptide 1 Analog Liraglutide (NN2211): A 12-week, double-blind, randomized, controlled trial Diabetes Care, June 1, 2004; 27(6): 1335 - 1342. [Abstract] [Full Text] [PDF]

				R. G. Bretzel, S. Arnolds, J. Medding, and T. Linn A Direct Efficacy and Safety Comparison of Insulin Aspart, Human Soluble Insulin, and Human Premix Insulin (70/30) in Patients With Type 2 Diabetes Diabetes Care, May 1, 2004; 27(5): 1023 - 1027. [Abstract] [Full Text] [PDF]

				B. Ahmad Review: Pharmacology of insulin The British Journal of Diabetes & Vascular Disease, January 1, 2004; 4(1): 10 - 14. [Abstract] [PDF]

				K. Hermansen, T. Ronnemaa, A. H. Petersen, S. Bellaire, and U. Adamson Intensive Therapy With Inhaled Insulin via the AERx Insulin Diabetes Management System: A 12-week proof-of-concept trial in patients with type 2 diabetes Diabetes Care, January 1, 2004; 27(1): 162 - 167. [Abstract] [Full Text] [PDF]

				M. R. Burge and J. D. Carey Vitiligo Associated With Subcutaneous Insulin Lispro Infusion in Type 1 Diabetes Diabetes Care, January 1, 2004; 27(1): 275 - 276. [Full Text] [PDF]