MON-560 The Myth Between Type 2 Diabetes Mellitus, Hemoglobin A1C and Maple Syrup Urine Disease

Abstract Disclosure: B. Zaidan: None. M. Pennant: None. Background: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by a defect in the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex, essential for metabolizing branched-chain amino acids (BCAAs): isoleucine, leucine, and valine. These amino acids are crucial for cellular signaling, cholesterol synthesis, energy production, and mTOR pathway regulation. Leucine activates mTORC1, affecting insulin sensitivity (1). Excessive BCAA intake can elevate mTORC1 activity, leading to insulin resistance and type 2 diabetes (2,3). Case-control studies link BCAA metabolism to insulin resistance and diabetes risk (4). Though HbA1c data in MSUD adults is limited, a case report describes a 4-year-old with MSUD and type 1 diabetes, managed with dietary changes and insulin (2,3). Case description: A 40-year-old male with a medical history of maple syrup urine disease (MSUD), anxiety, and prediabetes has experienced multiple hospitalizations due to MSUD crises. His most recent admission was complicated by acute leucine encephalopathy, raising concerns about the progression to type 2 diabetes mellitus (T2DM). The underlying triggers for these metabolic crises have often been unclear. During hospitalization, the patient adhered to a strict dietary regimen, limiting protein intake to a maximum of 45 grams per day. He was maintained on MSUD-specific formulas, such as Ketonex, designed to provide essential nutrients while minimizing leucine, isoleucine, and valine intake. His glucose intolerance was closely monitored even before the T2DM diagnosis through HbA1C and blood glucose measurements. Over the years, his HbA1C levels varied, 5.4%, 6.5%, and most recently 5.6%. While his early glucose values were within the normal range, prior to and around the time of T2DM diagnosis, a higher reading with an average of 126 mg/dL, with the highest of 418 mg/dL and a lowest of 72 mg/dL (normal range: 74-109 mg/dL). What made this case unique was the challenge of managing his impaired glucose tolerance without worsening MSUD. Individuals with MSUD require pure starch and simple sugars to maintain balanced branched-chain amino acids (BCAA) levels. During this hospitalization, we adopted a dietary strategy that maintained adequate simple carbohydrate intake while continuing Ketonex supplementation. Conclusion: This case underscores the necessity of timely and appropriate management in patients with MSUD to prevent severe complications. A multidisciplinary treatment approach is crucial to navigate the intricacies of the disease, dietary adherence, and psychological health. Future efforts should focus on improving care coordination and patient education to enhance the quality of life for individuals with this complex condition. Presentation: Monday, July 14, 2025