The adverse effects of persistent wound stress on patients with type 2 diabetes. Part 1: Pathophysiological...

Persistent wound stress is an important but easily neglected driver of chronic nonhealing wounds and organ dysfunction in patients with type 2 diabetes mellitus. This review summarizes how the diabetic internal environment, including hyperglycemia, insulin resistance, oxidative stress, vascular damage and immune dysregulation, reshapes the wound microenvironment and disturbs the orderly sequence of hemostasis, inflammation, proliferation and remodeling. We outline the clinical and pathophysiological features of type 2 diabetes mellitus and describe the pathological features of impaired wound healing, such as barrier disruption, microcirculatory disturbance, susceptibility to infection and long lasting inflammatory and oxidative states. We further discuss abnormalities in wound healing at tissue, cellular and molecular levels, with emphasis on impaired angiogenesis, neuropathy, imbalance of extracellular matrix turnover and dysregulated growth factors. On this basis, we highlight persistent wound stress as a central link that connects local lesions with systemic injury involving the cardiovascular system, kidneys, immune system and nervous system. Understanding this cycle from local wound to systemic injury and back to the wound provides a mechanistic framework for diabetic chronic wounds and suggests that effective management should address both the wound microenvironment and systemic metabolic and inflammatory stress.