New extreme insulin resistance type discovered: nonhypoglycaemic insulin autoimmune syndrome

A novel type of extreme insulin resistance, characterized by very high total insulin and very low free insulin levels, has been found to be caused by high-affinity insulin autoantibodies with a large capacity, reveals a study.

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

This study sought 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.

The authors examined a patient with IAS who never experienced hypoglycaemia but had persistent hyperglycaemia and extreme insulin resistance on treatment with 200 U of intravenous insulin daily. They then measured immunoreactive insulin (IRI), free insulin, and total insulin, as well as the ratio of free insulin to total insulin (insulin-free ratio [IFR]).

Free insulin and IRI were not detectable in the patient upon admission. Total insulin was more than 20,160 pmol/L, and the IFR was lower than 0.03 percent (control, 90.9 percent). The IRI remained undetectable after adding 500 U porcine insulin to the precipitate containing insulin antibodies.

When the patient initiated glucocorticoid therapy, his free insulin steadily increased to 11.16 pmol/L, his total insulin decreased to 5,040 pmol/L, and his IFR rose to 18.26 percent. Intravenous insulin was then discontinued, with good glycaemic control.

“The IFR can be used to evaluate therapeutic effects,” the authors said.