OBJECTIVES: Diabetes mellitus (DM) is a health issue affecting millions of people worldwide. Prolonged hyperglycemia increases the risk of pathological fractures
however, verifying this risk through bone analysis is challenging because of the heterogeneity of bone. METHODS: The systemic effects of type 2 DM (T2DM) on calcified tissues were investigated by examining dentin in mice, focusing on the underlying cellular and molecular mechanisms. Mouse incisor dentin was selected because of its continuous growth, similar to the annual rings of wood, offering a unique opportunity to study the time-dependent deterioration of calcified tissue affected by T2DM. RNA sequencing of pulp-derived cells was used to identify transcriptomic alterations in a db/db mouse model (BKS.cg-Lepr[db]/Lepr[db]Jc). Structural and mechanical changes in dentin were evaluated using Raman spectroscopy and nanoindentation. RESULTS: There was an increase in dentin volume in diabetic mice, accompanied by a deterioration in mechanical properties, particularly in primary dentin. This mechanical deterioration is likely to be associated with an inflammation-driven formation of abnormal dentin matrix caused by long-term hyperglycemia. No significant differences were observed in cross-linked collagen structures or advanced glycation end products. CONCLUSIONS: The findings demonstrated that gene expression in T2DM affects dentin and bone, contributing to micro-structural fragility through protein production. The incisor model used in this study proved to be a versatile tool for assessing other diseases that affect the integrity of calcified tissues over time.