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Diabetes precision medicine

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Type 1 diabetes reversed using precision medicine

A team of physicians from Texas Children’s Hospital, Baylor College of Medicine and the University of California, San Francisco, recently described a remarkable case of a precision/personalized medicine approach that eliminated the need for a Type 1 diabetes (T1D) patient to take insulin to maintain optimal blood sugar levels. Their description was outlined in a letter published in October 2020 in the New England Journal of Medicine. The treatment they developed specifically targets an underlying genetic mutation, which was the primary driver of the patient’s diabetes.

“To the best of our knowledge, this is the first example of a T1D patient who has experienced a complete reversal of insulin-dependence, and we are excited by the prospect that this could be a viable therapeutic strategy for a subset of T1D patients,” said corresponding author Dr. Lisa R. Forbes, deputy director for clinical services and community outreach for the Texas Children’s William T. Shearer Center for Human Immunobiology and assistant professor of Pediatrics, Immunology, Allergy and Retrovirology at Baylor.

T1D is a chronic condition in which the pancreas produces little to no insulin, a hormone that maintains sugar levels in the blood. Multiple factors, both genetic and environmental, contribute to the condition. Although it usually appears during childhood or adolescence, it can also develop in adults, and there is a global trend towards an increased prevalence of T1D. Traditional treatment options available to T1D patients are built around managing blood sugar levels with insulin, diet and exercise to prevent further complications.

The patient the physician team described in their letter is a young male who was diagnosed with a classic autoimmune presentation of T1D at when he was 17 years old. In addition to T1D, he had also experienced recurrent respiratory infections. The combination of these findings led to his referral to Dr. Forbes’ team.

The quest to find answers

A deeper investigation into the patient’s genome revealed that he harbored a harmful mutation in the gene STAT1 (signal transducer and activator of transcription 1) that dangerously heightened the activity of the STAT1 protein. This diagnosis explained the patient’s many seemingly unrelated clinical problems — other mutations that boost STAT1 activity are known to drive respiratory infections as well as various autoimmune conditions, including T1D.

The patient was started on a regimen of ruxolitinib, a potent inhibitor of the Jak/STAT signaling pathway. Over the next few months, this treatment significantly lowered the frequency of the patient’s chronic infections and — strikingly — reduced his dependence on insulin to control his blood sugar levels.

Hope for the future

A year after the initiation of therapy (and close to two years after his T1D diagnosis), the young man was able to discontinue daily injections of insulin and maintain normal blood glucose levels.

“This case was quite fascinating,” said Dr. Sophia Ebenezer, Texas Children’s physician, assistant professor of pediatric endocrinology at Baylor and a lead author of the letter. “This is the first clinical demonstration that Ruxolitinib can reverse insulin-dependence in T1D patients with STAT1 mutations, which is a very exciting prospect.”