SAT-542 Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke Like Symptoms - a rare cause of diabetes mellitus.

Abstract Disclosure: E. Triantafyllou: None. M. Williams: None. M. Cardenas Ona: None. P. Madhavan: None. Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke Like Symptoms (MELAS) is a rare, multi-system disorder usually caused by a mutation in the mitochondrial MT-TL1 gene which impairs mitochondrial protein synthesis. This can result in defective oxidative phosphorylation and decreased ATP availability. Prominent effects of MELAS occur in tissues with high energy utilization such as in the brain and muscles, resulting in the clinical presentation of neurological deficits and lactic acidosis. Despite an unclear etiology, proposed mechanisms for diabetes mellitus (DM) in the setting of MELAS include insufficient insulin release due to low ATP levels, lowered tissue insulin sensitivity due to oxidative damage, and lactate-driven gluconeogenesis since lactate is a major substrate for gluconeogenesis. Case: A 45-year-old female with a past medical history of DM and gestational diabetes, started to develop neurological symptoms as outlined below 2 years after diagnosis of DM. Her initial neurological symptoms included focal seizures, headaches, gait imbalance, and transient expressive aphasia. Labs also were notable for elevated lactic acid levels from 3.0- 2.4 mmol/L (.5-2.2). After extensive evaluation with neurology, she was diagnosed to have MELAS. Her family history is significant for early-onset cerebrovascular accidents (CVA) and diabetes. Her physical exam was notable for a BMI of 20, Blood pressure 100/70 mmHg, heart rate of 90 bpm, mild left lower extremity weakness and gait instability. Additional testing including GAD antibodies, islet cell antibodies, and C-peptide levels were unrevealing. She was receiving pioglitazone, sulphonylurea and empagliflozin in the initial presentation, but her glycemic control was suboptimal. Due to concerns of low bone density, the pioglitazone was discontinued, and she was switched from sulfonylurea to insulin due to suboptimal glycemic control. The Empagliflozin was continued. Discussion: Type 2 diabetes secondary to MELAS is a rare but important diagnostic consideration for individuals presenting with atypical DM and neurological deficits. These patients pose unique treatment challenges as they may have normal BMI and be prone to developing lactic acidosis. Dipeptidyl peptidase 4 (DPP4) inhibitors are considered a good option for this group of patients. Our patient unfortunately was not a good candidate for a DPP4 inhibitor due to elevated pancreatic enzyme level and was initiated on insulin. Further studies may be needed to evaluate optimal DM management options in these patients. Presentation: Saturday, July 12, 2025