A Novel Type of Extreme Insulin Resistance: Nonhypoglycemic Insulin Autoimmune Syndrome

Extreme insulin resistance is caused by genetic defects intersecting with the insulin action pathway or by the insulin receptor antibodies. Insulin autoimmune syndrome (IAS) is not considered one of the causes of extreme insulin resistance.

This work aimed to expand the current knowledge of extreme insulin resistance and to propose the diagnostic criteria and management strategy of a novel type of extreme insulin resistance.

A patient with IAS never experienced hypoglycemia but had persistent hyperglycemia and extreme insulin resistance with treatment with 200 U of intravenous insulin per day. Immunoreactive insulin (IRI), free insulin, and total insulin were measured. The ratio of free insulin to total insulin (insulin-free ratio, IFR) was calculated.

Extreme insulin resistance has not been reported to be caused by IAS. At admission, IRI and free insulin were undetectable in our patient; total insulin was more than 20 160 pmol/L; and the IFR was lower than 0.03% (control, 90.9%). After adding 500 U porcine insulin to the precipitate containing insulin antibodies, the IRI was still undetectable. Since the patient started glucocorticoid therapy, the free insulin has gradually increased to 11.16 pmol/L, his total insulin has decreased to 5040 pmol/L, and the IFR has increased to 18.26%. Intravenous insulin was stopped, with good glycemic control.

High-affinity insulin autoantibodies with a large capacity can induce a novel type of extreme insulin resistance characterized by extremely high total insulin and very low free insulin levels. The IFR can be used to evaluate therapeutic effects.