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Glycation (non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. [1] Typical sugars that participate in glycation are glucose , fructose , and their derivatives.
Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes. A systematic review has found that diabetic peripheral neuropathy affects 30% of diabetes patients. [ 1 ]
Proximal diabetic neuropathy, also known as diabetic amyotrophy, is a complication of diabetes mellitus that affects the nerves that supply the thighs, hips, buttocks and/or lower legs. Proximal diabetic neuropathy is a type of diabetic neuropathy characterized by muscle wasting, weakness, pain, or changes in sensation/numbness of the leg.
Glycosylation also plays a role in cell-to-cell adhesion (a mechanism employed by cells of the immune system) via sugar-binding proteins called lectins, which recognize specific carbohydrate moieties. [2] Glycosylation is an important parameter in the optimization of many glycoprotein-based drugs such as monoclonal antibodies. [6]
However, diabetes does cause higher morbidity, mortality and operative risks with these conditions. [41] Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increases rates of skin ulcers (diabetic foot ulcers) and infection and, in serious cases, necrosis and gangrene. It is why it ...
Thus modified, these proteins contribute to complications from diabetes. AGEs affect nearly every type of cell and molecule in the body and are thought to be one factor in aging [6] and some age-related chronic diseases. [7] [8] [9] They are also believed to play a causative role in the vascular complications of diabetes mellitus. [10]
In mouse models, excess levels of SAM have been implicated in erroneous methylation patterns associated with diabetic neuropathy. SAM serves as the methyl donor in cytosine methylation, which is a key epigenetic regulatory process. [18] Because of this impact on epigenetic regulation, SAM has been tested as an anti-cancer treatment.
SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. [2] [3] As of 2014, several medications of this class had been approved or were under development. [4]