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Background  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.    Results  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.    Conclusions  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.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13148-021-01109-2.

Genome‑wide profiling of DNA methylation and gene expression unravel the epigenetic landscape in diabetes-related hypothyroidism