Autoimmune Insulin Dysregulation Syndromes

Autoimmune insulin dysregulation syndromes encompass a spectrum of rare disorders in which the immune system produces antibodies that bind to insulin or its receptor, leading to unpredictable glycaemic excursions. These conditions range from insulin autoimmune syndrome, marked by spontaneous hypoglycaemia in the absence of exogenous insulin, to type B insulin resistance, characterised by severe hyperglycaemia due to autoantibodies targeting the insulin receptor. The pathogenesis involves high‐affinity or high‐capacity antibody–insulin complexes that alter the bioavailability and clearance of insulin, while receptor‐blocking antibodies impede insulin signalling at target tissues. Clinically, patients present with recurrent hypoglycaemic or hyperglycaemic episodes that are refractory to conventional management and may be misdiagnosed as factitious disorder or insulinoma. Diagnosis requires demonstration of insulin–antibody complexes or receptor autoantibodies, often using gel filtration chromatography, polyethylene glycol precipitation or mass spectrometry. Therapeutic strategies include dietary modification, agents that delay carbohydrate absorption, immunomodulation with corticosteroids, rituximab or other immunosuppressants, and, in extreme cases, plasmapheresis to remove pathogenic antibodies. Despite the rarity of these syndromes, their study has yielded insights into autoantibody biology, insulin kinetics and personalised approaches to endocrine autoimmunity.

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Autoimmune Insulin Dysregulation Syndromes publication trend

The graph below shows the total number of articles in autoimmune insulin dysregulation syndromes across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin Autoimmune Syndrome (IAS): A condition of spontaneous hypoglycaemia caused by autoantibodies binding endogenous insulin, leading to delayed insulin release and recurrent low-glucose episodes.

Anti-Insulin Antibodies (IAs): Immunoglobulins directed against insulin that form circulating complexes, altering insulin clearance and bioavailability.

Type B Insulin Resistance: A severe form of insulin resistance driven by autoantibodies that block insulin receptor function, resulting in extreme hyperglycaemia and often acanthosis nigricans.

Gel Filtration Chromatography: A laboratory technique that separates free insulin from high-molecular-weight insulin-antibody complexes to quantify unbound hormone levels.

References

1. When discordant insulin and C-peptide levels lead to a medical diagnosis in a patient with transient hypoglycemia: Varying degrees of interference of insulin-antibody complexes on three insulin immunoassays. Heliyon (2024).
2. Diagnosis of insulin autoimmune syndrome using polyethylene glycol precipitation and gel filtration chromatography with ex vivo insulin exchange. Clinical Endocrinology (2016).
3. Successful Treatment of Type B Insulin Resistance With Rituximab. The Journal of Clinical Endocrinology & Metabolism (2015).
4. Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome. The Journal of Clinical Endocrinology & Metabolism (2018).
5. Insulin Autoimmune Syndrome: A Systematic Review. International Journal of Endocrinology (2023).
6. Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study. Frontiers in Endocrinology (2023).