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

Autor: Church DS; Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; The University of Cambridge MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK., Barker P; Core Biochemical Assay Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Burling KA; Core Biochemical Assay Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Shinwari SK; Diabetes & Endocrinology Centre, Birmingham Heartlands Hospital, Birmingham, UK., Kennedy C; Department of Diabetes and Endocrinology, Beaumont Hospital, RCSI Medical School Dublin, Dublin, Ireland., Smith D; Department of Diabetes and Endocrinology, Beaumont Hospital, RCSI Medical School Dublin, Dublin, Ireland., Macfarlane DP; Department of Diabetes & Endocrinology, Raigmore Hospital, Inverness, UK., Kernohan A; Department of Diabetes and Endocrinology, Queen Elizabeth University Hospital, Glasgow, UK., Stears A; National Severe Insulin Resistance Service, Wolfson Diabetes & Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Karamat MA; Diabetes & Endocrinology Centre, Birmingham Heartlands Hospital, Birmingham, UK., Whyte K; West Glasgow Ambulatory Care Hospital, Glasgow, UK., Narendran P; Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, UK., Halsall DJ; Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Semple RK; The University of Cambridge MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.; University of Edinburgh Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK.
Jazyk: angličtina
Zdroj: Diabetic medicine : a journal of the British Diabetic Association [Diabet Med] 2023 Nov; Vol. 40 (11), pp. e15194. Date of Electronic Publication: 2023 Sep 01.
DOI: 10.1111/dme.15194
Abstrakt: 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.
(© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)
Databáze: MEDLINE
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