Shared mechanisms of musculoskeletal dysfunction in type 2 diabetes mellitus: Insights into future therapeutic directions (Review)
TL;DR
Although the manifestations of T2DM differ among skeletal muscle, tendon, TBI and bone, these tissues share common pathological drivers, including metabolic dysregulation, chronic inflammation, oxidative stress, extracellular matrix remodeling, and impaired regenerative capacity.
Abstract
Type 2 diabetes mellitus (T2DM) profoundly affects the musculoskeletal system through multifactorial mechanisms. The present review systematically summarizes the impact of T2DM on skeletal muscle, tendon, tendon-bone interface (TBI), and bone, highlighting their shared and tissue-specific pathophysiological pathways. In skeletal muscle, impaired insulin signaling and mitochondrial dysfunction lead to reduced protein synthesis, enhanced proteolysis, and muscle atrophy. In tendons, advanced glycation end products accumulation and microangiopathy disrupt collagen metabolism and biomechanics. At the TBI, persistent hyperglycemia induces fibrocartilage fibrosis, impaired angiogenesis and disorganized stress transmission, ultimately weakening load-bearing capacity. In bone, the imbalance between osteoblast and osteoclast activity, coupled with microvascular dysfunction and metabolic acidosis, results in reduced bone formation and increased fragility. Although the manifestations of T2DM differ among skeletal muscle, tendon, TBI and bone, these tissues share common pathological drivers, including metabolic dysregulation, chronic inflammation, oxidative stress, extracellular matrix remodeling, and impaired regenerative capacity. A deeper understanding of these shared mechanisms may facilitate the identification of novel therapeutic targets. Emerging technologies, including single-cell RNA sequencing, regenerative medicine, and precision medicine, further provide new opportunities for early diagnosis and personalized management of diabetes-related musculoskeletal disorders.