Exploration of autophagy-associated genes and potential molecular mechanisms in type 1 diabetes and osteoporosis.

Abstract

The co-occurrence of osteoporosis (OP) and type 1 diabetes mellitus (T1DM) represents a clinically significant comorbidity pattern, characterized by skeletal fragility and insulin deficiency. While epidemiological links exist, their shared molecular mechanisms remain undefined. This study investigates autophagy-a critical cellular degradation pathway-as a potential mechanistic bridge between OP and T1DM pathogenesis. We integrated multi-omics approaches using GEO datasets to identify autophagy- associated hub genes. Machine learning (LASSO/Random Forest) prioritized CPNE1 and FRAT2, validated through ROC curve analysis. Functional annotation via GO/KEGG enrichment analyses revealed enrichment in disease-associated pathways, corroborated by immune infiltration profiling and single-cell RNA sequencing showing cell-type-specific expression patterns. miRNA-gene regulatory networks further elucidated post-transcriptional control mechanisms. Our integrated analyses suggest that CPNE1 and FRAT2 may represent novel targets for combined diagnosis and therapy in OP and T1DM, where autophagic dysregulation could contribute to comorbid pathogenesis. These insights offer fresh perspectives for developing dual-disease management approaches.