SAT087 Maternally Inherited Diabetes And Deafness: Support For SGLT2 Inhibitor Use

Disclosure: S. Pandya: None. K. Selk: None. Introduction: Maternally inherited diabetes and deafness (MIDD) is a rare genetic disease resulting from a mitochondrial mutation. There is a wide phenotypic expression secondary to heteroplasmy. The clinical manifestations of MIDD are hyperglycemia, sensorineural hearing loss, maculopathy, cardiac conduction defects, myopathy/poor exercise tolerance, and neuropathy. Diabetes mellitus generally occurs during the third decade of life, and there tends to be rapid progression to insulin therapy with reported earlier onset of microvascular complications. Here we present a case of MIDD successfully treated long-term with empagliflozin and linagliptin. Clinical Case: A 36-year-old male with sensorineural hearing loss presented with a 20-pound unintentional weight loss, polyphagia, and polydipsia. His blood glucose level was 300 mg/dL and HbA1c was 14.3%. His mother carried a diagnosis of type 2 diabetes mellitus and his grandmother had latent autoimmune diabetes of adulthood. Prior to presenting to endocrinology, he had been started on metformin, glipizide, and linagliptin with ongoing poor glycemic control. Given his presentation, family history, and lean habitus with BMI of 20, he was assessed for possible autoimmune diabetes. Testing for glutamic acid decarboxylase 65-kilodalton isoform antibody (GAD65), islet cell antibody, tyrosine phosphatase-related islet antigen 2 (IA2), and zinc transporter 8 antibody (ZNT8) was unrevealing. A C-peptide level was detectable but <1 ng/mL. His sulfonylurea was discontinued, and he was started on basal insulin with a dramatic improvement in his glycemic control. He was later able to discontinue insulin therapy. However, given poor exercise tolerance and his known hearing loss, he was seen by genetics where he underwent testing and was found to have a m.3243 A>G mutation in MT-TL1 gene making the diagnosis of MIDD. Metformin was discontinued due to a possible risk of lactic acidosis and sitagliptin was initiated. Due to hyperglycemia, empagliflozin was added and he was later transitioned to empagliflozin-linagliptin to reduce his pill burden. He has continued to have a1c levels of 6.5% or less for the last 3 years and periodic C-peptide measurements have been >1 ng/mL. Conclusion: Given MIDD is a rare form of monogenic diabetes, treatment tends to be individualized with many transitioning to insulin early in their disease course. Given the reported increased risk for microvascular complications, sodium-glucose cotransporter-2 (SGLT2) inhibitors are an attractive therapeutic agent. However, there is little literature on the use of these agents in MIDD and there is concern about the risk for diabetic ketoacidosis given insulin use is required by many afflicted individuals. This case highlights the safety of long-term empagliflozin in a patient with MIDD. Presentation: Saturday, June 17, 2023