Diagnosis and treatment of anti‐insulin antibody‐mediated labile glycaemia in insulin‐treated diabetes

David S. Church, Peter Barker, Keith A. Burling, Shah K. Shinwari, Carmel Kennedy, Diarmuid Smith, David P. Macfarlane, Andrew Kernohan, Anna Stears, Muhammad A. Karamat, Karen Whyte, Parth Narendran, David J. Halsall, Robert K. Semple*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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: 40 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: 27 people had insulin immunoreactivity (IIR) below 3,000 pmol/L that fell to below 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3,000 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 patients IIR was below 3,000 pmol/L but fell by more than 50% after PEG precipitation. 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.
Original languageEnglish
JournalDiabetic Medicine
Early online date10 Aug 2023
Publication statusE-pub ahead of print - 10 Aug 2023

Keywords / Materials (for Non-textual outputs)

  • Diabetes mellitus
  • gel filtration chromatography
  • Hirata disease
  • immunoassay
  • anti-insulin antibodies
  • insulin autoimmune syndrome
  • polyethylene glycol


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