Diabetes-induced cardiovascular disease

Abstract

In this paper a broad overview of the onset of cardiovascular disease through diabetic-induced mechanisms is given. Risk factors for DMII, like obesity, a bad diet and stress are accompanied with oxidative stress. Oxidative stress leads to insulin resistance because of impairment in the signaling cascade of the insulin receptor. Insulin resistance leads to hyperglycemia and hyperglycemia results in the glycation of proteins in plasma and the extracellular matrix. The glycated proteins will eventually crosslink with each other leading to the formation of advanced glycation end-products (AGE). The receptor for AGE is RAGE and stimulation of it leads to the stimulation of NF-kB. NF-kB is a transcription factor complex that can induce expression of more RAGE, free radicals, adhesion molecules, chemokines and cytokines. An inflammatory response in the endothelial cells will thus occur, leading to the attraction of monocytes, platelets and cytokines. Possible inhibitors of inflammation, such as NO, are eliminated by the oxidative stress occurring in DMII. This leads to a pro-atherogenic phenotype. Platelets in diabetes are hyperactive so clotting reactions will occur accelerated. The upregulated expression of coagulation factors also contribute to amplification of clotting reactions. Altered levels of other plasma components like TF and PAI-I will further contribute to the pro-thrombotic state. All of these symptoms initially caused by DMII will lead to a higher probability of developing cardiovascular disease.