BioChem - DOS

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

Diabetic medicine : a journal of the British Diabetic Association

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.; Whyte, Karen; Narendran, Parth; Halsall, David J.; Semple, Robert K.

<P><B>Abstract</B></P><P><B>Aims</B></P><P>Anti&#8208;insulin antibodies in insulin&#8208;treated diabetes can derange glycaemia, but are under&#8208;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.</P><P><B>Methods</B></P><P>Forty people with insulin&#8208;treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad&#8208;specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation.</P><P><B>Results</B></P><P>Twenty&#8208;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.</P><P><B>Conclusions</B></P><P>Anti&#8208;insulin antibodies should be considered in insulin&#8208;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.</P>

2023

0742-3071

1464-5491

40

11

pp.e15194

10.1111/dme.15194

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART126860348

anti&#x2010; insulin antibodies; diabetes mellitus; gel filtration chromatography; Hirata disease; immunoassay; insulin autoimmune syndrome; polyethylene glycol;