Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes
Church, David S Barker, Peter Burling, Keith A Shinwari, Shah K Kennedy, Carmel Smith, Diarmuid Macfarlane, David P Kernohan, Andrew Stears, Anna Karamat, Muhammad A
Church, David S
Barker, Peter
Burling, Keith A
Shinwari, Shah K
Kennedy, Carmel
Smith, Diarmuid
Macfarlane, David P
Kernohan, Andrew
Stears, Anna
Karamat, Muhammad A
Abstract
Aims: Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making.
Methods: Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation.
Results: Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate.
Conclusions: Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.
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Date
2023-08-10
Type
Article
Subject
Endocrinology
Collections
Citation
Church DS, Barker P, Burling KA, Shinwari SK, Kennedy C, Smith D, Macfarlane DP, Kernohan A, Stears A, Karamat MA, Whyte K, Narendran P, Halsall DJ, Semple RK. Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes. Diabet Med. 2023 Aug 10:e15194. doi: 10.1111/dme.15194. Epub ahead of print. PMID: 37562398.
Journal / Source Title
Diabetic Medicine
DOI
10.1111/dme.15194
PMID
37562398
Publisher
Wiley
Publisher’s URL
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-5491