7923 Latent Autoimmune Diabetes of Adulthood (LADA) Complicating Common Variable Immunodeficiency (CVID)

Abstract Disclosure: L. Pathak: None. M.G. Jakoby: None. Introduction: CVID is caused by defective B-lymphocyte maturation that results in immunoglobulin deficiency. Patients with CVID are predisposed to both infections and autoimmune disorders, with approximately 20% experiencing at least one autoimmune complication. We present a patient with LADA complicating CVID. Case A 31-year-old woman was referred for newly diagnosed diabetes mellitus (DM). Medical history was notable for primary hypothyroidism and apparent chronic lymphocytic thyroiditis. A presumptive diagnosis of type 2 DM was made due to obesity, and the patient was treated with metformin. However, she could not tolerate the medication due to diarrhea. Semaglutide was substituted and tolerated without adverse effects. During the first six months of treatment with semaglutide 0.5 mg weekly, HbA1c improved from 6.4 to 5.6%. However, in the next six months, HbA1c increased to 6.6% despite full compliance with medication and stable weight. Anti-glutamic acid decarboxylase (GADA) titer was unequivocally elevated at 69.8 IU/mL (0.0-5.0), though anti-insulin and islet antigen-2 (IA-2) antibodies were undetectable. Insulin glargine was added to the patient’s diabetes regimen, and HbA1c improved to 5.5% three months later. Discussion This patient meets Immunology of Diabetes Society diagnostic criteria for LADA, namely diabetes diagnosed in adulthood (≥ 30 y), elevated diabetes-associated autoantibody titer, and insulin independence for at least six months after diagnosis. Patients with high-titer GADA tend to be younger and have more rapid and significant loss of β-cell function than patients with low GADA titers, and this patient’s rapidly waning glycemic response to semaglutide conforms with this observation. Until recently, autoimmune diabetes in the setting of CVID was thought to be an unusual complication, though the prevalence of type 1 diabetes among CVID patients in the European Society for Immunodeficiency registry is 1.6%, approximately four-fold higher than the general European population. LADA shares genetic features linked to childhood-onset type 1 DM, making it possible or evenly likely that LADA has occurred in cases of CVID, though a careful search of PubMed failed to identify reported cases. This patient illustrates the importance of considering LADA in CVID, particularly with abrupt loss of glycemic response to noninsulin therapeutic agents. Presentation: 6/1/2024