Type 2 diabetes mellitus (T2DM) and hypothyroidism are two common endocrine diseases and the phenomenon that the prevalence of diabetes-related hypothyroidism shows a significant upward trend deserves further attention, but the specific pathogenesis is not yet clear. The study aimed to explore the molecular mechanisms on DNA methylation regulating gene expression and participating in diabetes-related hypothyroidism through genome-wide DNA methylation and RNA sequencing. The prevalence of hypothyroidism in T2DM patients was significantly higher than that in patients without T2DM (P = 0.018). Meanwhile, high TSH and low T3 and T4 levels were detected in diabetic mice. Low T3 and T4 levels were detected in Nthy-ori3-1 cells incubated in high-glucose medium. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were detected by RNA sequencing and reduced representation bisulfite sequencing in Nthy-ori3-1 cells cultured in high-glucose and normal medium. Functional enrichment analyses reveled that DMRs and DEGs were related to significant pathways including Ras, Wnt and MAPK pathways. We observed the potential connection between T2DM and hypothyroidism. This study was the first one carrying out DNA methylation and gene expression profiles to explore epigenetic modification in diabetes-related hypothyroidism, which provided information for the detailed study of the molecular mechanism in diabetes-related hypothyroidism.

中文翻译：

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DNA甲基化和基因表达的全基因组分析揭示了糖尿病相关甲状腺功能减退症的表观遗传景观

2型糖尿病（T2DM）和甲状腺功能减退症是两种常见的内分泌疾病，糖尿病相关甲状腺功能减退症的患病率呈明显上升趋势的现象值得进一步关注，但具体发病机制尚不明确。本研究旨在通过全基因组DNA甲基化和RNA测序，探索DNA甲基化调控基因表达和参与糖尿病相关甲状腺功能减退的分子机制。T2DM 患者甲状腺功能减退的患病率显着高于非 T2DM 患者（P = 0.018）。同时，在糖尿病小鼠中检测到高 TSH 和低 T3 和 T4 水平。在高葡萄糖培养基中培养的 Nthy-ori3-1 细胞中检测到低 T3 和 T4 水平。在高葡萄糖和正常培养基中培养的 Nthy-ori3-1 细胞中，通过 RNA 测序和还原代表性亚硫酸氢盐测序检测差异表达基因 (DEG) 和差异甲基化区域 (DMR)。功能富集分析表明，DMR 和 DEG 与包括 Ras、Wnt 和 MAPK 途径在内的重要途径有关。我们观察到 T2DM 与甲状腺功能减退之间的潜在联系。本研究首次开展DNA甲基化和基因表达谱研究，探索糖尿病相关甲状腺功能减退的表观遗传修饰，为深入研究糖尿病相关甲状腺功能减退的分子机制提供信息。功能富集分析表明，DMR 和 DEG 与包括 Ras、Wnt 和 MAPK 途径在内的重要途径有关。我们观察到 T2DM 与甲状腺功能减退之间的潜在联系。本研究首次开展DNA甲基化和基因表达谱研究，探索糖尿病相关甲状腺功能减退的表观遗传修饰，为深入研究糖尿病相关甲状腺功能减退的分子机制提供信息。功能富集分析表明，DMR 和 DEG 与包括 Ras、Wnt 和 MAPK 途径在内的重要途径有关。我们观察到 T2DM 与甲状腺功能减退之间的潜在联系。本研究首次开展DNA甲基化和基因表达谱研究，探索糖尿病相关甲状腺功能减退的表观遗传修饰，为深入研究糖尿病相关甲状腺功能减退的分子机制提供信息。