Diabetes mellitus: Complications, emerging therapeutic targets, and evolving treatment approaches

Abstract

Diabetes Mellitus (DM) is a chronic metabolic disorder effecting the carbohydrate, protein and lipid metabolism, primarily caused by elevated blood glucose levels, due to the insulin deficiency or impaired glucose uptake by the body cells. Its clinical manifestations including polydipsia, polyuria, polyphagia, blurry vision, extreme fatigue can lead to severe complications such as diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy imposing substantial global health and economic burdens. This review synthesizes current evidence on the pathophysiology and clinical spectrum of DM complications, highlighting the roles of glucotoxicity, lipotoxicity, oxidative stress, advanced glycation end-products, mitochondrial dysfunction, maladaptive inflammation, and microvascular rarefaction. Additionally, emerging biomarkers linked to the pathogenesis of diabetic complications are summarized and reviewed. The novel therapeutic targets, include glucokinase, AMPK, SIRT1, SIRT3, GPR120 activators, TGR5, GPR119 agonists, PTP1B and G-FAT inhibitors as next generation drugs. Advanced treatment strategies encompass gene and cell-based approaches next-generation drug delivery systems-nanocarriers, nanopumps, closed-loop “smart” insulin technologies. We also review applications of artificial intelligence and machine learning for early detection, progression prediction, treatment optimization and personalized care, alongside insights from recent clinical trials and innovation trends in the patent landscape.