USE OF HUMAN INSULIN IN WOUND HEALING IN PATIENTS WITH DIABETES: MECHANISMS AND FUTURE PERSPECTIVES. REVIEW

• DOI: https://doi.org/10.22533/at.ed.8208122624028

• Palavras-chave: Diabetes mellitus; Insulin; Tissue repair; Topical treatment; Cellular mechanisms.

• Keywords: Diabetes mellitus; Insulin; Tissue repair; Topical treatment; Cellular mechanisms.

• Abstract:

  This review explores how insulin, in addition to participating in glycemic control, acts directly on wound healing, especially in diabetic patients. Chronic hyperglycemia damages skin proteins (such as collagen and elastin) through the formation of advanced glycation end products (AGEs), impairing tissue recovery. This damage aggravates chronic inflammation, reduces angiogenesis, and compromises cellular repair function. Studies show that locally administered insulin via drip can reverse some of these effects, accelerating healing without significant risks of systemic hypoglycemia. The research highlights the molecular mechanisms that explain the difficulty of healing in diabetics and points to a reassessment of the therapeutic potential of topical insulin. The focus is on understanding and exploring how insulin acts in the healing of chronic wounds in diabetic patients.
  Methods: This review is based on a critical survey of the literature indexed in PubMed and MEDLINE (2000–2025), with a search guided by descriptors such as "topical insulin," "diabetic wound healing," and "molecular mechanisms of insulin in tissue repair." Clinical trials, preclinical studies (in vitro and in animal models), systematic reviews, and conceptual articles addressing the local effects of human insulin on skin repair were included. Studies restricted to systemic insulin therapy were excluded. The selection prioritized biological relevance, methodological soundness, and contribution to the understanding of cellular mechanisms and clinical implications. The findings were organized into four axes: pathophysiology of diabetic healing, molecular signaling of insulin, clinical evidence, and translational perspectives.
  Results: Clinical trials have explored interventions for hard-to-heal wounds, targeting molecular, cellular, and tissue processes such as inflammation, angiogenesis, and oxidative stress. Despite progress, there is no single effective solution for all cases. Personalized strategies, combining therapies according to the cause of the wound, show promise for improving outcomes. Continued research and standardized protocols are essential to advance the treatment of these complex injuries.
  Discussion: The ability of local insulin to simultaneously modulate oxidative stress, chronic inflammation, and angiogenesis positions it as a unique intervention in the scenario of therapies for diabetic ulcers, where isolated approaches often fail. Unlike recombinant growth factors, whose high cost limits access in public systems, regular human insulin is generic, registered in the SUS (Brazilian Unified Health System), and can be incorporated into low-cost formulations, such as hydrogels. However, the lack of consensus on optimal concentration, frequency of application, and outcome criteria makes it difficult to compare studies and implement standardized clinical protocols.
  Conclusion: Human insulin shows potential to accelerate healing in diabetics, with robust evidence of cellular mechanisms and reduced complications. Advances in pharmaceutical formulations and combination therapies may overcome challenges such as standardization and safety, integrating it into chronic wound management.