Insulin Antibodies in Ætiology of Labile Diabetes

Dixon, K.; Exon, P.D.; Hughes, H

doi:10.1016/s0140-6736(72)92841-3

Cited by 61 publications

(34 citation statements)

References 8 publications

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“…Such a variability in insulin pharmacokinetics might result in a labile glycaemic control (23). It has been suggested that insulin antibodies may act as a buffer, binding circulating insulin and releasing it slowly, thereby stabilising glycaemic control (24,25). Accordingly, it was anticipated that patients with elevated levels of insulin antibodies would have a smaller day-to-day variation in insulin pharmacokinetics.…”

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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“…Other possible effects of insulin antibodies are less clear. Andersen [8] showed that the presence of antibodies was associated with a reduction in the honeymoon period independent of the level of diabetic control and the hypothesis that insulin antibody might 'buffer' the effect of circulating insulin [9] has not been substantiated. We report a study of the relationship between changes in insulin antibody, insulin dose and diabetic control in established diabetics changing from ordinary bovine soluble and isophane to highly purified porcine equivalents and the effects of rechallenge with the original insulins.…”

Section: Discussionmentioning

confidence: 99%

The effect of insulin antibodies on insulin dose and diabetic control

1982

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Summary.In a single blind randomised cross-over study, 40 patients were changed from ordinary bovine to highly purified porcine insulins for a period of 6 months. Half were later rechallenged with bovine insulin. Sequential determinations of IgG insulin binding capacity for bovine insulin were correlated with insulin dose and diabetic control. After changing to highly purified insulins the following correlations were observed between percentage change in insulin dose and change in insulin binding capacity: at 2 months r = 0.35 (p < 0.05), at 4 months r = 0.38 (p < 0.02) and at 6 months r = 0.37 (p < 0.02). When the patients who showed substantial changes in HbA~ were removed from the analysis, the remaining 29 demonstrated a clearer relationship between these two variables (r = 0.56,p < 0.01). Removal of patients with a low initial insulin binding capacity left 18 patients with stable diabetes, and changes in insulin binding capacity and insulin dose showed an even closer correlation for this group (r = 0.77, p < 0.001). A similar degree of positive correlation was observed after rechallenge with bovine insulin. We conclude that the level of circulating insulin antibody affects the dose of insulin required to maintain stable diabetic control.Key words: Insulin, insulin antibody, diabetic control.Most patients treated with ordinary bovine insulins develop circulating insulin antibodies [1]. Higt/ly purified porcine insulins are much less immunogenic and patients changing to these insulins often experience a reduction in insulin requirement [2,3], a fall in circulating insulin binding capacity [4] and an increase in circulating levels of free insulin [5]. Although antibody mediated insulin resistance is unusual [6], injection site lipoatrophy is a common complication of the use of ordinary bovine insulins [7]. Other possible effects of insulin antibodies are less clear. Andersen [8] showed that the presence of antibodies was associated with a reduction in the honeymoon period independent of the level of diabetic control and the hypothesis that insulin antibody might 'buffer' the effect of circulating insulin [9] has not been substantiated. We report a study of the relationship between changes in insulin antibody, insulin dose and diabetic control in established diabetics changing from ordinary bovine soluble and isophane to highly purified porcine equivalents and the effects of rechallenge with the original insulins. Patients and MethodsThe practice of one hospital diabetologist was surveyed to identify all the patients aged between 16 and 65 years who had had diabetes for at least 3 years and had been treated regularly with ordinary bovine soluble and isophane insulins for at least that time. Those who were blind or pregnant or who had other serious medical or psychological illness were excluded. Fifty-nine of the 71 eligible patients consented to be studied and 40 completed the 18 month protocol. These 14 women and 26 men were aged between 16 and 64 years (mean 40 years). The age at diagnosis ranged from 2 to 5...

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“…It has been suggested [14,15] that in patients who have no endogenous insulin secretion, high insulin antibody binding may improve diabetic control by prolonging the half-life of insulin [16,17]. Thus, C-peptide non-secretors with low insulin antibody binding might be expected to gain particular advantage from an evening dose of insulin.…”

Section: Discussionmentioning

confidence: 99%