Lai Valerie, Shahidi Mariam, Chan Alicia, Jain-Ghai Shailly
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Division of Endocrinology and Metabolism, University of Alberta, Edmonton, AB, Canada.
Endocrinol Diabetes Metab Case Rep. 2023 Mar 29;2023(1):22-0413. doi: 10.1530/EDM-22-0413.
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency is an inborn error of metabolism resulting in a lack of ketogenesis and leucine catabolism. Hallmarks of decompensation include hypoglycemia without ketosis (or hypoketosis), metabolic acidosis, and hyperammonemia. Management includes avoiding fasting and restricting dietary protein and fat. Conversely, type 2 diabetes mellitus (T2DM) requires carbohydrate restriction and/or anti-hyperglycemic agents; thus, managing these co-existing disorders is challenging. A 36-year-old male with HMG-CoA lyase deficiency and T2DM (Hemoglobin A1c (HbA1c): 7.9%) presented with confusion and shock. Blood work revealed metabolic acidosis, hyperammonemia, hyperglycemia, and hypoketosis. The patient was diagnosed with hyperosmolar non-ketotic hyperglycemia and hyperammonemia secondary to HMG-CoA lyase metabolic decompensation requiring intensive care unit admission. Hyperammonemia management was challenging because alternative calories with i.v. dextrose (due to hyperglycemia) and i.v. lipids (due to HMG-CoA lyase deficiency) could not be provided as usual. The patient was started on hemodialysis and i.v. insulin with marked improvement. Once stabilized, metformin and insulin were initiated. T2DM impaired cellular glucose uptake and produced a state similar to hypoglycemia, despite the patient being profoundly hyperglycemic, which led to metabolic decompensation of HMG-CoA lyase deficiency. Managing T2DM and HMG-CoA lyase deficiency warrants special considerations due to the potential for metabolic decompensation with both hyperglycemia and hypoglycemia.
In a patient with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency and type 2 diabetes mellitus (T2DM), management principles include avoiding hypoglycemia to prevent metabolic decompensation, providing insulin for proper glucose utilization, and moderation of carbohydrate intake to prevent consequences of chronic hyperglycemia. The development of insulin resistance in the form of T2DM in HMG-CoA lyase deficiency likely triggered a state similar to hypoglycemia, leading to cellular energy deficiency and subsequently metabolic decompensation. It is important to avoid hypoglycemia in patients with HMG-CoA lyase deficiency and T2DM, as the risk of metabolic decompensation is increased due to the lack of ketogenesis in HMG-CoA lyase deficiency. Selection of antidiabetic agents in this patient population requires careful consideration, and agents that have a higher risk of hypoglycemia should be avoided.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）裂解酶缺乏症是一种先天性代谢缺陷，导致酮体生成和亮氨酸分解代谢缺乏。失代偿的特征包括无酮血症（或低酮血症）的低血糖、代谢性酸中毒和高氨血症。治疗措施包括避免禁食以及限制饮食中的蛋白质和脂肪。相反，2型糖尿病（T2DM）需要限制碳水化合物摄入和/或使用降糖药物；因此，同时管理这些并存的疾病具有挑战性。一名36岁患有HMG-CoA裂解酶缺乏症和T2DM（糖化血红蛋白（HbA1c）：7.9%）的男性出现意识模糊和休克。血液检查显示存在代谢性酸中毒、高氨血症、高血糖和低酮血症。该患者被诊断为继发于HMG-CoA裂解酶代谢失代偿的高渗性非酮症高血糖和高氨血症，需要入住重症监护病房。高氨血症的管理具有挑战性，因为无法像往常一样通过静脉输注葡萄糖（由于高血糖）和静脉输注脂质（由于HMG-CoA裂解酶缺乏）来提供替代热量。患者开始接受血液透析和静脉注射胰岛素，病情有明显改善。病情稳定后，开始使用二甲双胍和胰岛素。尽管患者血糖极高，但T2DM导致细胞葡萄糖摄取受损并产生类似于低血糖的状态，这导致了HMG-CoA裂解酶缺乏症的代谢失代偿。由于存在高血糖和低血糖导致代谢失代偿的可能性，管理T2DM和HMG-CoA裂解酶缺乏症需要特别考虑。
在患有3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）裂解酶缺乏症和2型糖尿病（T2DM）的患者中，治疗原则包括避免低血糖以防止代谢失代偿，提供胰岛素以促进葡萄糖的适当利用，以及适度控制碳水化合物摄入以防止慢性高血糖的后果。HMG-CoA裂解酶缺乏症患者中以T2DM形式出现的胰岛素抵抗可能引发类似于低血糖的状态，导致细胞能量缺乏，进而引起代谢失代偿。对于患有HMG-CoA裂解酶缺乏症和T2DM的患者，避免低血糖很重要，因为HMG-CoA裂解酶缺乏导致酮体生成缺乏，从而增加了代谢失代偿的风险。在这一患者群体中选择抗糖尿病药物需要仔细考虑，应避免使用低血糖风险较高的药物。
