Chanoine Jean-Pierre, Thompson David M, Lehman Anna
Endocrinology and Diabetes Unit, Department of Pediatrics, BC Children's Hospital and The University of British Columbia, Vancouver, British Columbia, Canada.
Division of Endocrinology, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
Diabetes. 2025 Feb 1;74(2):153-163. doi: 10.2337/db24-0515.
Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized primarily by hearing impairment and diabetes. m.3243A>G, the most common phenotypic variant, causes a complex rewiring of the cell with discontinuous remodeling of both mitochondrial and nuclear genome expressions. We propose that MIDD depends on a combination of insulin resistance and impaired β-cell function that occurs in the presence of high skeletal muscle heteroplasmy (approximately ≥60%) and more moderate cell heteroplasmy (∼25%-72%) for m.3243A>G. Understanding the complex mechanisms of MIDD is necessary to develop disease-specific management guidelines that are presently lacking.
母系遗传糖尿病和耳聋（MIDD）是一种线粒体疾病，主要特征为听力障碍和糖尿病。m.3243A>G是最常见的表型变异，会导致细胞内复杂的重新布线，伴随线粒体和核基因组表达的不连续重塑。我们提出，MIDD取决于胰岛素抵抗和β细胞功能受损的共同作用，这种情况发生在骨骼肌异质性较高（约≥60%）且m.3243A>G的细胞异质性更为中等（约25%-72%）的情况下。了解MIDD的复杂机制对于制定目前尚缺乏的疾病特异性管理指南至关重要。
