SUN-545 Diabetes & Mitochondrial Dysfunction: A Case of G[3243] Mutation with MELAS Potential

Abstract Disclosure: H.C. Davuluri: None. K. Kaur: None. N. Kharkongor Chengappa: None. E.I. Krug: None. A 28-year-old male with a history of type 2 diabetes mellitus, diagnosed during preemployment screening, was evaluated in an outpatient setting. During this evaluation, labs revealed an HbA1c of 7.4% and a positive C-peptide level of 2.7 (normal range: 1.1-4.4). The patient’s autoimmune panel, which included insulin antibodies (<5), GAD 65 antibodies (<5), ZNT8 antibodies (<15), and IA2 antibodies (<7.5), was negative, ruling out autoimmune causes of diabetes. Additional labs, including a basic metabolic panel (BMP) and lipid panel, were unremarkable. He was initially started on metformin, and, following follow-up visits, insulin therapy and a GLP-1 agonist were introduced for improved glycemic control. However, the patient was lost to follow-up for a significant period until late 2024, when he was found unresponsive early in the morning and subsequently presented to the emergency department (ED). His family reported that he had been diaphoretic and tremulous prior to being found unresponsive. His home medications included glargine (15 units with the last dose 24 hours prior) and weekly Ozempic injections (last dose 5 days ago). His home blood glucose was measured at 11 mg/dL. Notably, the patient had experienced a loss of appetite and significant weight loss (20 pounds over the past few weeks), which he attributed to the Ozempic. Of particular concern was the patient’s recent diagnosis of a genetically confirmed G[3243] mitochondrial mutation, identified at an outside facility in Boston. His family history revealed a strong predisposition to MELAS, with maternal cousins and his mother, who died at 53 years old exhibiting symptoms highly suggestive of MELAS, including diabetes, chronic kidney disease (CKD), deafness, and other clinical manifestations. Given this background, ddx included progression to MELAS, potential insulin overdose due to reduced appetite, and the possibility of suicide. Emergency interventions included the initiation of dextrose-containing fluids, an octreotide drip, and a high-carb diet. Over the next few days, the patient showed significant improvement in both his mental status and laboratory results. He was ultimately discharged with a plan to continue Ozempic and to add antioxidant therapy, including high-dose coenzyme Q10, vitamin D, vitamin C, and riboflavin—all known to support mitochondrial function. Upon follow-up, the patient showed significant improvement in hyperglycemia and fatigue with semaglutide therapy and antioxidant supplementation. Discussion: The presented patient is a highly complex case of genetically confirmed G[3243] mitochondrial mutation, with a strong family history of MELAS. The majority of individuals with this mutation typically develop MIDD (maternally inherited diabetes and deafness), while approximately 10% progress to MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome). Presentation: Sunday, July 13, 2025