SUN-275 Azathioprine for Tertiary Prevention of Diabetes in Patients with Newly Diagnosed Type 1 Diabetes

Background: Co-occurrence of type 1 diabetes (T1DM) and autoimmune hepatitis (AIH) is rare(1). Older studies on azathioprine for tertiary prevention of T1DM show mixed results and often intolerable side effects. (2,3) There are no recent studies or case reports on the effect of azathioprine on the tertiary prevention of T1DM. Clinical Case: A 6 y.o. M with recently diagnosed AIH on prednisolone taper (15 mg BID; 2mg/kg/day) presented to pediatric endocrinology due to abnormal labs including glucose of 684 mg/dL. He endorsed abdominal pain and polydipsia but was otherwise well. Further workup showed VBG: pH 7.4, bicarbonate 26.7, glucose 653mg/dL, C-peptide 4.7, HgbA1c 6.6%. He was given IV fluids and started on basal/bolus insulin regimen. He was positive for 5/5 diabetes related autoantibodies: Glutamic Acid Decarboxylase Antibody: >250 IU/mL [Ref Range: <5 IU/mL], Insulin Antibody: 8.3 U/mL [Ref Range: <0.4 U/mL], Islet Cell Antibody Screen: POSITIVE [Ref Range: NEGATIVE]; Reflex, Islet Cell Antibody Titer: 80 JDF units [Ref Range: < 1.25 JDF units], IA-2 Antibody: 7.8 U/mL[Ref Range: <0.8 U/mL], ZnT8 Antibody: >500 U/mL [Ref Range: <15 U/ml]. His hepatitis was well controlled and over a period of a few weeks his corticosteroids were weaned and azathioprine was started as treatment for his AIH. As his corticosteroid dose was decreased, his insulin requirements decreased; after he was weaned off corticosteroids he was weaned off insulin a few weeks later. He has not required insulin now for over 1 year since diagnosis, with most recent HgbA1c 5.5%. He is continued on azathioprine for his AIH with good control of his hepatitis and without significant medication side effects. Conclusion: This is one of the first recent case reports showing the possible positive effect of azathioprine in tertiary prevention of T1DM. This patient's results may be more dramatic since the onset of hyperglycemia was associated with corticosteroids. Recent trials of immunotherapy in the prevention and treatment of T1DM have focused more on targeted immunomodulation, but in certain cases azathioprine may still be beneficial.(4) More studies of immune modulation therapies for preventing and treating T1DM are needed. References: 1.Kremer Hovinga, ICL et al. A girl with type 1 diabetes and a yellowish appearance. BMJ Case Report. 2010 Nov 26 published online. 2.Cook, JJ, et al. Double-Blind Controlled Trial of Azathioprine in Children with Newly Diagnosed Type I Diabetes. Diabetes, vol. 38, no. 6, June 1989, pp. 779-783. 3.Silverstein, Janet, et al. Immunosuppression with Azathioprine and Prednisone in Recent-Onset Insulin-Dependent Diabetes Mellitus. New England Journal of Medicine, vol. 319, no. 10, 1988, pp. 599-604. 4. Ryden AKE et al. Non-antigenic and antigenic interventions in type 1 diabetes. Human Vaccines & Immunotherapeutics. April 2014;10(4):838-46.