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A very interesting case of Type 1 diabetes reversal has been reported.

The boy, then 17, has not had to take insulin for almost 2 years. Recovery of pancreatic beta-cell function remains a challenge because type 1 diabetes is not reversible, even early in the disease. Signal transducer and activator of transcription 1 (STAT1) gain of function is a monogenic syndrome associated with a heterozygous mutation in STAT1. A number of autoimmune conditions develop in patients with this syndrome, including type 1 diabetes and susceptibility to infection. At age 15, the boy presented with a history of chronic mucocutaneous candidiasis, chronic diarrhea, oral and rectal ulcers, recurrent sinopulmonary infections, and a condition called hypogammaglobulinemia which impairs the immune system and increases risk for infection. Then, at the 17 years of age, he received a diagnosis of type 1 diabetes.

Nine months after the diagnosis of type 1 diabetes, reassessment of the patient’s clinical picture with the constellation of type 1 diabetes caused concern regarding an underlying immune dysregulation disorder. Tests showed a pathogenic mutation in STAT1 that confirmed the diagnosis of STAT1 gain-of-function disease. A medication called ruxolitinib, an inhibitor of Janus kinase (JAK) 1 and 2, was previously shown to decrease many of the symptoms of this disorder. The patient subsequently began to receive ruxolitinib at a dose of 10 mg twice daily. Over the next few months, treatment led to resolution of the chronic mucocutaneous candidiasis and autoimmunity, decreased frequency of infection, and decreased use of exogenous insulin. A total of 21 months after the patient received a diagnosis of type 1 diabetes and 12 months after the initiation of ruxolitinib therapy – exogenous insulin was discontinued, and the patient had normal ranges of glucose in the blood.

Although this patient did not receive insulin for almost 2 years now, it remains conceivable that this was a long lasting effect. More time will be needed to assess the permanence of this reversal but indicates that type 1 diabetes may be reversed in young adults. Further study is warranted on how JAK inhibition led to this clinical outcome and perhaps its broader use for the treatment of type 1 diabetes.

For more information visit: https://www.nejm.org/doi/full/10.1056/NEJMc2022226

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