Diabetes mellitus and diabetic foot ulcer: Etiology, biochemical and molecular based treatment strategies via gene and nanotherapy

Diabetes mellitus (DM) is a collection of metabolic and pathophysiological disorders manifested with high glucose levels in the blood due to the inability of β-pancreatic cells to secrete an adequate amount of insulin or insensitivity of insulin towards receptor to oxidize blood glucose. Nevertheless, the preceding definition is only applicable to people who do not have inherited or metabolic disorders. Suppose a person who has been diagnosed with Type 1 or Type 2DM sustains an injury and the treatment of the damage is complicated and prolonged. In that case, the injury is referred to as a diabetic foot ulcer (DFU). In the presence of many proliferating macrophages in the injury site for an extended period causes the damage to worsen and become a diabetic wound. In this review, the scientific information and therapeutic management of DM/DFU with nanomedicine, and other related data were collected (Web of Science and PubMed) from January 2000 to January 2022. Most of the articles revealed that standard drugs are usually prescribed along with hypoglycaemic medications. Conversely, such drugs stabilize the glucose transporters and homeostasis for a limited period, resulting in side effects such as kidney damage/failure, absorption/gastrointestinal problems, and hypoglycemic issues. In this paper, we review the current basic and clinical evidence about the potential of medicinal plants, gene therapy, chemical/green synthesized nanoparticles to improving the metabolic profile, and facilitating the DM and DFU associated complications. Preclinical studies also reported lower plasma glucose with molecular targets in DM and DFU. Research is underway to explore chemical/green synthesized nanoparticle-based medications to avoid such side effects. Hence, the present review is intended to address the current challenges, recently recognized factors responsible for DM and DFU, their pathophysiology, insulin receptors associated with DM, medications in trend, and related complications.