Immunosuppressive combo quells type B insulin resistance
SEP 24, 2018- Reuters Health News –
Combined immunosuppressive therapy is highly effective against a rare but potentially deadly and hard-to-control type of diabetes, according to a prospective study.
This approach is recommended for managing “one of the most severe forms of diabetes—type B insulin resistance due to the autoantibodies against the insulin receptor,” Dr. Joanna Klubo-Gwiezdzinska told Reuters Health by email.
The prevalence of the condition is unknown. Only 104 cases have been reported in the literature, according to a paper online September 10 in Diabetes Care.
In the paper, Dr. Klubo-Gwiezdzinska of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, Bethesda, Maryland, and colleagues say the condition is “characterized by diabetes refractory to massive doses of insulin, severe hypercatabolism, hyperandrogenism, and a high mortality rate.”
The researchers had previously successfully treated seven patients using combined immunosuppressive therapy. For the current study, they recruited 22 patients, all but one of whom showed fasting hyperglycemia. Nineteen were women. The median age at diagnosis was 42, and the most common underlying autoimmune diseases were lupus (40.9%) and mixed connective tissue disease (31.8%).
At baseline, median fasting glucose was 307 mg/dL and HbA1c was 11.8%. Total testosterone in the women was 126 ng/dL (compared to a normal of 8 to 60), and daily insulin requirement was 1,775 units.
Patients were treated with regular or concentrated U-500 insulin and insulin sensitizers. They also received rituximab, high-dose pulsed steroids, and cyclophosphamide until remission, followed by maintenance therapy with azathioprine.
After a median of 5 months, 19 patients (86%) achieved remission; they discontinued insulin and achieved a normal fasting glucose of 80 mg/dL and a median HbA1c of 5.5%. Testosterone in the women fell to 28 ng/mL.
Over a median follow-up of 6 years, three patients had recurrence that responded to repeated therapy. None of the patients died.
“The study has important clinical implications,” added Dr. Klubo-Gwiezdzinska. The immunosuppression regimen “has changed the natural history of this disease, from 54% mortality to a curable form of diabetes, and as such should be recommended in patients with type B insulin resistance.”
Commenting by email, endocrinologist Dr. Lavanya Viswanathan, whose work was cited in the paper, told Reuters Health that this “very rare form of insulin resistance… may be missed as a potential diagnosis and more exposure to such research encourages better diagnosis and paves way for better research models as well.”…