Autoimmune hypoglycaemia: a narrative review from the laboratory perspective

Abstract

: Whilst hypoglycaemia is common, autoimmune causes are relatively rare. Autoimmune causes of hypoglycaemia includes both insulin autoimmune syndrome (IAS), and type B insulin resistance syndrome (TBIR). IAS typically presents with post-prandial hypoglycaemia in adulthood and is characterised by inappropriately high plasma insulin, proinsulin and C-peptide concentrations during hypoglycaemia, with C-peptide:insulin molar ratios of <1, high insulin autoantibody titres and the presence of macroinsulin. TBIR typically presents with hyperglycaemia due to insulin resistance as a result of insulin receptor antibodies. TBIR may, however, also present with endogenous hyperinsulinaemic hypoglycaemia or hyperglycaemia-hypoglycaemia depending on the activating or inhibiting action of the insulin receptor antibodies. Very rarely, autoimmune hypoglycaemia may be due to insulin antibodies raised to therapeutic insulin or insulin-binding paraproteins with purported mechanisms similar to IAS in producing hypoglycaemia. This review summarises the pathophysiology and laboratory features of IAS and TBIR, and highlights the importance of considering these diagnoses in patients with hypoglycaemia associated with non-suppressed insulin levels, to prevent unnecessary pancreatic surgery.