Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes

Anders Lindholm, Lisbeth B. Jensen, Philip D. Home, Philip Raskin, Bernhard O. Boehm, Jacob Råstam

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)876-882
Number of pages7
JournalDiabetes Care
Volume25
Issue number5
DOIs
StatePublished - May 2002

Fingerprint

Insulin Aspart
Biphasic Insulins
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Insulin Antibodies
Insulin
Antibody Formation
Antibodies
Short-Acting Insulin
Safety
Subcutaneous Injections
North America
Radioimmunoassay
Meals
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes. / Lindholm, Anders; Jensen, Lisbeth B.; Home, Philip D.; Raskin, Philip; Boehm, Bernhard O.; Råstam, Jacob.

In: Diabetes Care, Vol. 25, No. 5, 05.2002, p. 876-882.

Research output: Contribution to journalArticle

Lindholm, Anders ; Jensen, Lisbeth B. ; Home, Philip D. ; Raskin, Philip ; Boehm, Bernhard O. ; Råstam, Jacob. / Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes. In: Diabetes Care. 2002 ; Vol. 25, No. 5. pp. 876-882.
@article{227d33cab22f436a80098a6dfd9aacbf,
title = "Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes",
abstract = "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.",
author = "Anders Lindholm and Jensen, {Lisbeth B.} and Home, {Philip D.} and Philip Raskin and Boehm, {Bernhard O.} and Jacob R{\aa}stam",
year = "2002",
month = "5",
doi = "10.2337/diacare.25.5.876",
language = "English (US)",
volume = "25",
pages = "876--882",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "5",

}

TY - JOUR

T1 - Immune responses to insulin aspart and biphasic insulin aspart in people with type 1 and type 2 diabetes

AU - Lindholm, Anders

AU - Jensen, Lisbeth B.

AU - Home, Philip D.

AU - Raskin, Philip

AU - Boehm, Bernhard O.

AU - Råstam, Jacob

PY - 2002/5

Y1 - 2002/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036580827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036580827&partnerID=8YFLogxK

U2 - 10.2337/diacare.25.5.876

DO - 10.2337/diacare.25.5.876

M3 - Article

C2 - 11978684

AN - SCOPUS:0036580827

VL - 25

SP - 876

EP - 882

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 5

ER -