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Insulin autoimmune syndrome
Other Resources UpToDate PubMed

Insulin autoimmune syndrome

Contributors: Ferda Tan, Eric Ingerowski MD, FAAP, Paritosh Prasad MD
Other Resources UpToDate PubMed


Emergent Care / Stabilization:
Intravenous (IV) glucose infusion to stabilize hypoglycemia

Diagnosis Overview:
Insulin autoimmune syndrome (IAS), also known as Hirata disease, is a rare syndrome of intermittent hypoglycemia due to high circulating levels of autoantibodies to insulin. It is most prevalent among Asian individuals, as the suspected allele is more common in this population. It affects both sexes equally. The pathophysiology of this syndrome arises from the formation of insulin-insulin autoantibody complexes when insulin is released after a meal, resulting in a disconnect between glucose levels and free insulin concentrations. These autoantibodies have high binding capacity and low affinity. Due to the presence of these complexes, the binding of insulin to its receptors is ineffective, leading to hyperglycemia. This then signals the pancreatic beta cells to secrete more insulin, causing hyperinsulinemia. When the autoantibodies are saturated with insulin, glucose levels fall and the remaining complexes form a reservoir of insulin that spontaneously dissociates and does not cease, even when plasma glucose concentrations are low, leading to spontaneous hypoglycemia. 

Since many patients with IAS also have other autoimmune diseases, (most commonly Graves disease, rheumatoid arthritis, and systemic lupus erythematosus), many studies focused on methimazole and IAS. Studies demonstrate that IAS can be triggered by sulfhydryl and reducing drugs such as methimazole, alpha-lipoic acid, tiopronin, captopril, insulin, propranolol, and d-penicillamine.

Viral infections such as measles, mumps, rubella, varicella, and hepatitis C have also been reported to trigger IAS. 

Hence, history of autoimmune diagnoses or viral infections exposure serve as risk factors and predisposing medical history for IAS.

  • Hypoglycemia (especially postprandial) OR alternating episodes of hypoglycemia and hyperglycemia
  • Typical Whipple triad:
    1. Symptoms of hypoglycemia such as tremor, palpitation, anxiety, sweating, hunger, and sensory abnormalities
    2. Blood glucose < 2.8 mmol/l during episode
    3. Symptoms relieved quickly after administering glucose-increasing drugs
IAS is mostly a self-limiting disease with a good prognosis; removing triggers and using certain medications will eliminate symptoms and yield good outcomes (in the absence of serious complications).


E10.9 – Type 1 diabetes mellitus without complications

408539000 – Insulin autoimmune syndrome

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Last Reviewed:04/22/2024
Last Updated:04/24/2024
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Insulin autoimmune syndrome
A medical illustration showing key findings of Insulin autoimmune syndrome
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