Insulin antibody determination: Theoretical and practical considerations

Reeves, W G

doi:10.1007/bf00257336

Cited by 40 publications

(22 citation statements)

References 41 publications

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“…However, the latter hypothesis remains to be proven; in fact, de Meijer et al failed to demonstrate any significant difference in absorption rate of 125 Ilabelled soluble human insulin between patients with and without antibodies (16). The reason for this discrepancy is unknown, but it may relate to the inclusion of different patient groups as well as a different assay for insulin antibodies and for total and free insulin (21).…”

Section: Discussionmentioning

confidence: 99%

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

Jw¹,

Frystyk²,

Lauritzen³

et al. 2005

eur j endocrinol

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Objective: This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes. Methods: Twenty-three patients (8 women, 15 men) aged 44.8 (20.6-62.5) years (median and range) with diabetes duration of 19.5 (1.6 -44.6) years and haemoglobin (Hb)A 1C of 9.2% (8.1-12.3%) participated in the study, which consisted of 12-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA 1C and insulin antibodies were also determined. Results: Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75% (moderate vs high (%, median and range): 62 (15 -74) vs 80 (75 -89)). High levels of insulin antibodies resulted in about threefold increase in AUC (0 -24 h) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P , 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA 1C were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies. Conclusions: In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies. 153 907-913 European Journal of Endocrinology

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Section: Discussionmentioning

confidence: 99%

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

Jw¹,

Frystyk²,

Lauritzen³

et al. 2005

eur j endocrinol

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“…The production of insulin antibodies after insulin injection has been reported to play a role in the development of local and systemic allergic reactions, injection-site lipoatrophy and some types of insulin resistance as well as having more subtle effects on the dose requirement and on the pharmacokinetics of injected insulin [1]. It is therefore of paramount importance to document that therapeutic insulin is unlikely to cause antibody formation.…”

Section: Discussionmentioning

confidence: 99%

“…ELI-SA-data are presented as the ratio between the OD value for the day 30 sample and the OD value for the day 0 sample in a 1 : 500 dilution. TG, Transgenic mice munogenic preparations [1,3,[29][30][31]. Historically a high antibody titre in rabbits immunized with an insulin preparation is known often to predict a similar result in humans injected with the same preparation [29,30,32].…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies toward proteins administered for therapeutic purposes have been reported to play a role in allergic reactions and lipoatrophy at the injection site [1]. Moreover, antibodies directed against epitopes on the analogue could cross react with epitopes on the corresponding endogenous protein and lead to a neutralizing effect of both the analogue and the endogenous protein [2].…”

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confidence: 99%

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The potential immunogenicity of human insulin and insulin analogues evaluated in a transgenic mouse model

et al. 1994

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Summary Transgenic mice with tissue-specific expression of the human insulin gene in the beta cells of the pancreas do not produce insulin-specific antibodies when injected with human insulin. Tolerant transgenic mice injected with human or porcine insulin reflect the clinical situation. When injected with bovine insulin the transgenic mice produce antibodies. The potential immunogenicity of 12 recombinant human insulin analogues has been tested in this transgenic model. The analogues were designed either to prevent hexamer formation or to improve chemical stability or both. The analogues have amino acid substitutions or deletions at residue 8, 10 and 21 in the A-chain and residue 3, 9, 27 and 28 in the B-chain. The results show that substitution of single amino acids in the A-chain loop of human insulin for the corresponding amino acids in bovine insulin at residues A8 or A10 is sufficient to elicit an antibody response in responder mice. Only human insulin analogues with substitutions at residues 8 or 10 in the Achain elicit antibody formation in the transgenic mice, whereas non-transgenic control groups respond to insulin and all analogues. Antibodies developed against the human insulin analogues are cross reactive with recombinant human insulin. Antibodies developed against an immunogenic analogue could therefore neutralize both the analogue and the native insulin and thereby aggravate the patient's condition. This transgenic mouse immunogenicity model should be useful as an in vivo model to map immunogenic areas of recombinant proteins. [Diabetologia (1994[Diabetologia ( ) 37: 1178[Diabetologia ( -1185

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“…Furthermore, increased antibody affinity implies a slow dissociation of the insulin-antibody complex and therefore a lower clearance rate. In contrast, a low antibody affinity implies a rapid dissociation of the insulin-antibody complex, so that the antibodies will be more rapidly accessible to the catabolizing cells [7,[12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Disappearance rate of insulin antibodies after discontinuing insulin treatment in 42 Type 2 (non-insulin-dependent) diabetic patients

et al. 1984

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Summary.The disappearance rate of insulin antibodies was studied after cessation of insulin treatment which had been given for 3 months to 6 years in 42 Type 2 (non-insulin-dependent) diabetic patients. Insulin antibodies were measured before and 15 days after interruption of insulin treatment, and every 30 days until the disappearance of insulin antibodies. The mean + SD value of insulin binding in the entire group before the interruption of insulin treatment was 32 + 14%. There was no relationship between the antibody level at that time and the duration of insulin treatment. However, the insulin antibody level was significantly higher in 17 diabetic patients on an insulin dose of > 20 U/day (p < 0.02) than in 25 on an insulin dose of < 20 U/day (39 _+ 13% versus 28 _+ 12%). A positive correlation was found between intial insulin binding and the time required for it to fall below 10% (r = 0.74). Antibodies were absent 60 days after discontinuing insulin treatment in eight of ten subjects presenting with initial binding of < 20%. In contrast, in only two of 12 patients with an initial binding of > 40% were insulin antibodies detectable 150 days after discontinuation of insulin therapy. Disappearance of insulin antibodies sometimes took up to 1 year and occasionally even more than 2 years.

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Insulin antibody determination: Theoretical and practical considerations

Cited by 40 publications

References 41 publications

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

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

The potential immunogenicity of human insulin and insulin analogues evaluated in a transgenic mouse model

Disappearance rate of insulin antibodies after discontinuing insulin treatment in 42 Type 2 (non-insulin-dependent) diabetic patients

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