How does chronic high blood sugar in Type 2 diabetes lead to long-term damage in major organs, and what are the mechanisms underlying these complications

Abstract

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by sustained hyperglycemia, which brings on a host of pathogenic events leading to the development of long term organ damage. This paper seeks to explain how chronic elevations in blood sugar levels result in long-term damage to major organs through discussions on associated pathophysiological mechanisms and processes. The prevalence of T2D continues to rise globally; hence, it is a major public health and socioeconomic challenge. In a series of mechanisms, chronic hyperglycemia enhances cellular and metabolic injury by inducing oxidative stress, mitochondrial dysfunction, inflammation, endothelial damage, and production of
AGEs. These interrelated pathways result in the devastating complications of diabetic nephropathy, retinopathy, neuropathy, and cardiovascular disease, each contributing to increased morbidity and mortality. Oxidative stress in T2D results in the overproduction of ROS; these, in turn, damage cellular constituents and promote chronic inflammation. Also, mitochondrial dysfunction further increases ROS production, decelerates the ATP-producing machinery, and increases apoptosis.
Inflammatory responses resulting from persistent hyperglycemia are manifested by cytokine release that promotes tissue injury. Impaired endothelial function gives rise to vascular integrity disruption with restricted blood flow, thereby leading to some complications of nephropathy and retinopathy. The non-enzymatic reactions between sugar and proteins or lipids form AGEs, contributing to tissue rigidity and vascular complications with regard to the binding of receptors,
enhancing oxidative stress and inflammation. Diabetic nephropathy is one of the major causes of ESRD. This is characterized by reduced glomerular filtration rate and progressive glomerular injury mediated by AGEs and endothelial injury. Diabetic retinopathy is the damage to the blood vessels of the retina, leading to loss of vision due to abnormal and fragile proliferation of the vessels. Neuropathy involves degeneration of the nerves, thus impairing sensory and autonomic functions due to chronic oxidative stress and inflammation.