Sunday, April 15, 2018

Insulin autoimmune syndrome aka Hirata disease

It’s caused by spontaneous development of insulin antibodies (no prior exposure to insulin). If that’s the case why does it cause hypoglycemia and not just hyperglycemia? From a review:

Although the precise mechanism for hypoglycemia in IAS is unknown, the most widely accepted hypothesis is a mismatch between blood glucose and free insulin concentration, secondary to the binding and release of secreted insulin by autoantibodies.7 Following a meal or oral glucose load, glucose concentration in the bloodstream rises, providing a stimulus for insulin secretion. Autoantibodies bind to these insulin molecules, rendering them unavailable to exert their effects. The resultant hyperglycemia not only promotes further insulin release, but may also explain the increased hemoglobin A1c often seen in IAS patients.6 As glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. Insulin molecules spontaneously dissociate from the autoantibodies at this time, giving rise to a raised free insulin level inappropriate for the glucose concentration, evoking hypoglycemia.7 Insulin autoantibodies with a high binding capacity and a low affinity are more likely to bring about hypoglycemic symptoms.10 Medications containing a sulfhydryl group have been proposed to induce autoantibody formation by interacting with the disulfide bonds of the insulin molecule and augmenting its immunogenicity;11 however, the true underlying pathophysiology remains unclear at this time. Rarely, the co-existence of both insulin autoantibodies and insulin receptor autoantibodies within the same patient has been described.12

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