The research found that C57BL/6J mice fed a high-fat diet for 12 weeks exhibited increased body weight and fat mass, alongside elevated fasting blood glucose levels, indicative of diabetes.

Diabetic polyneuropathy was confirmed in these mice through reduced intraepidermal nerve fiber density and delayed paw withdrawal times in response to stimuli.

Single-cell RNA sequencing analyses indicated altered transcriptional profiles in periosteal cells due to diabetic neuropathy, which affects cellular signaling and communication between sensory nerves and bone cells.

Diabetes is associated with significant end organ damage, including polyneuropathy and alterations in bone health, with up to 50% of diabetic patients developing neuropathy that adversely affects their skeletal system.

A recent study investigates the effects of diabetic peripheral neuropathy on skeletal health, utilizing a mouse model of type 2 diabetes induced by a high-fat diet.

Additionally, the study revealed a significant reduction in long bone periosteum innervation, with TUBB3+ nerve fibers decreasing by 76% in the femur under high-fat diet conditions, along with notable decreases in sensory and sympathetic nerve fibers.

The findings underscore the interplay between nerve dysfunction and skeletal health in diabetes, suggesting that therapeutic strategies targeting nerve signaling could help mitigate bone disease in diabetic patients.

MicroCT analysis further revealed significant reductions in both cortical and trabecular bone parameters among high-fat diet-fed mice, indicating compromised bone structure, with reductions in bone volume and increased trabecular spacing.

Specific neuropeptides and growth factors derived from sensory neurons were identified as crucial for maintaining bone health, with potential disruptions in these signaling pathways contributing to diabetic bone disease.