Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia and disturbances in 
carbohydrate, lipid, and protein metabolism. Beyond classical metabolic derangements, diabetes induces profound 
immunometabolic remodeling that reshapes cellular energy utilization, immune functions, and tissue homeostasis. 
This remodeling plays a central role in the initiation and progression of diabetic complications, including 
cardiovascular disease, nephropathy, neuropathy, retinopathy, and nonalcoholic fatty liver disease (NAFLD). 
Immunometabolic changes involve chronic low-grade inflammation, immune cell dysregulation, increased 
production of reactive oxygen species (ROS), and alterations in nutrient-sensing pathways such as AMP-activated 
protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB). These 
pathways intersect with metabolic signaling to drive organ-specific toxicity and accelerate disease progression. 
This comprehensive review synthesizes current knowledge on immunometabolic interactions in diabetes, 
highlights mechanisms linking metabolic dysfunction and immune responses, and discusses the impact of 
immunometabolic remodeling on organ damage. We also evaluate emerging biomarkers and therapeutic strategies 
that modulate immunometabolic pathways to prevent or attenuate diabetic complications. A deeper understanding 
of immunometabolic remodeling offers new avenues for precision medicine in diabetes management.