Diabetic pathways

4 pathways of Diabetic Damage:

Advanced glycosylation pathway: AGEs build up intracellularly, which are damaged proteins covalently bonded with excess glucose. These also build up in the extracellular matrix leading to impaired cell signalling and function.

Polyol pathway: sorbital buildup causes lens opacification, but far more critically aldose reductase requires NADPH that would otherwise be available for Glutathionine reductase. As it is, lack of NADPH leads to global oxidative damage.

Protein Kinase c pathway: High intracellular glucose leads to increased DAG, overactivating Protein Kinase C, leading to increased selective gene expression causing: 1) decreased eNOS, increased ET-1, 2) increased VEGF, 3) increased TGF-beta leading to increased Collagen and fibronectin, 4) increased PAI-1 leading to decreased fibrinolysis, 5) increased necrosis factor beta (NF-kappa B), 6) increased NADPH oxidases leades to increased ROS (Reactive Oxygen Species).

Hexosamine pathway: Glycolysis creates fructose-6-PO4 some of which is diverted into a signalling pathway by GFAT, ultimately becoming UDP N-acetyl glucosamine, which when attached to serine and threonine residues activates gene expression that is pathological when disregulated.

Electron Transport Chain Pathway: Too much glucose in the cell leads to overuse of the TCA cycle and overgeneration of electrons via the electron transport chain. These electrons are backed up at coenzyme Q, attaching instead directly to Oxygen forming superoxide and damaging the mitochondrial interior.



Micro vascular Damage causes
1. Nephropathy
2. Retinopathy
3. Distance sensory neuropathy (4 types are sensory, motor, autonomic dysfunction, gastroparesis)

Pattern of weakness