Antiglycation
A large body of evidence suggests that advanced glycosylation endproducts (AGEs) are important pathogenetic mediators of almost all diabetes complications, conventionally grouped into micro or macro-angiopathies. For instance, AGEs are found in retinal vessels of diabetic patients, and their levels correlate with those in serum as well as with severity of retinopathy. AGEs are now implicated in age related degradation from coronary disease to skin aging.
Anti-Glycation (or anti-AGEs) represents a new prophylactic effect against glycosylation or glycation. Anti-Glycation is becoming an important therapeutic defensive benefit against endogenous and exogenous aging factors leading to glycation. Put another way, Anti-Glycation is the inhibition of the chemical reaction between sugar radicals and proteins leading to glycation.
Anti-AGE drugs are being intensively studied. Aminoguanidine was the first drug designed to inhibit glycation reactions by inhibiting the conversion of early products to AGEs. Animal studies proved that aminoguanidine is beneficial for many diabetes-related complications. Additional drugs that inhibit AGE formation or disrupt already formed AGEs (e.g., AGE-breakers) are also under active investigation.
Aminoguanidine, has also been shown to prevent retinopathy in diabetic animals. It is also known that AGEs accumulate in peripheral nerves of diabetic patients and that the use of anti-AGE agents improves nerve conduction velocities and neuronal blood flow abnormalities. It is further known that the characteristic structural changes of diabetic nephropathy, thickened glomerular basement membrane and mesangial expansion, are accompanied by accumulation of AGEs, leading to glomerulosclerosis and interstitial fibrosis. Prolonged infusion of nondiabetic rats with AGEs has led to the development of similar morphological changes and significant proteinuria.
Aminoguanidine prevented diabetic nephropathy in diabetic animal models and was recently shown to do the same in one clinical trial on diabetic patients. Atherosclerosis is significantly accelerated in diabetic patients and is associated with greater risk of cardiovascular and cerebrovascular mortality. Animal and human studies have shown that AGEs play a significant role in the formation and progression of atherosclerotic lesions. Increased AGE accumulation in the diabetic vascular tissues has been associated with changes in endothelial cell, macrophage, and smooth muscle cell function.
In addition, AGEs can modify LDL cholesterol in such a way that it tends to become easily oxidized and deposited within vessel walls, causing streak formation and, in time, atheroma. AGE-crosslink formation results in arterial stiffening with loss of elasticity of large vessels. This arterial stiffness has recently been shown to be reversed by the administration of another anti-AGE class of compounds called AGE-breakers.
Unfortunately we all have to worry about AGEs. AGEs is implicated in the process of aging and many diseases. Current evidence points to glucose, not only as the body’s main short-term energy source, but also as the long-term fuel of diabetes complications, mainly in the form of oxidative, pro-inflammatory AGEs. Foods high in sugar need to be avoided, and food commonly consumed after exposure to heat contains a significant amount of pre-formed AGEs, a fact that offers a new perspective on food as a major environmental risk factor.
Published studies have suggested that High fructose corn syrup decreases glucose tolerance, increases insulin resistance, and speeds up the process of glycation – contributing to complications of diabetes and aging. Sugar's major drawback is that it raises the insulin level, which inhibits the release of growth hormones, which in turn depresses the immune system. Harvard researchers recently reported that women who drank one or more sugar-sweetened soft drinks per day were 83% more likely to develop type 2 diabetes than women who drank less than one a month.
Anti-Glycation (or anti-AGEs) represents a new prophylactic effect against glycosylation or glycation. Anti-Glycation is becoming an important therapeutic defensive benefit against endogenous and exogenous aging factors leading to glycation. Put another way, Anti-Glycation is the inhibition of the chemical reaction between sugar radicals and proteins leading to glycation.
Anti-AGE drugs are being intensively studied. Aminoguanidine was the first drug designed to inhibit glycation reactions by inhibiting the conversion of early products to AGEs. Animal studies proved that aminoguanidine is beneficial for many diabetes-related complications. Additional drugs that inhibit AGE formation or disrupt already formed AGEs (e.g., AGE-breakers) are also under active investigation.
Aminoguanidine, has also been shown to prevent retinopathy in diabetic animals. It is also known that AGEs accumulate in peripheral nerves of diabetic patients and that the use of anti-AGE agents improves nerve conduction velocities and neuronal blood flow abnormalities. It is further known that the characteristic structural changes of diabetic nephropathy, thickened glomerular basement membrane and mesangial expansion, are accompanied by accumulation of AGEs, leading to glomerulosclerosis and interstitial fibrosis. Prolonged infusion of nondiabetic rats with AGEs has led to the development of similar morphological changes and significant proteinuria.
Aminoguanidine prevented diabetic nephropathy in diabetic animal models and was recently shown to do the same in one clinical trial on diabetic patients. Atherosclerosis is significantly accelerated in diabetic patients and is associated with greater risk of cardiovascular and cerebrovascular mortality. Animal and human studies have shown that AGEs play a significant role in the formation and progression of atherosclerotic lesions. Increased AGE accumulation in the diabetic vascular tissues has been associated with changes in endothelial cell, macrophage, and smooth muscle cell function.
In addition, AGEs can modify LDL cholesterol in such a way that it tends to become easily oxidized and deposited within vessel walls, causing streak formation and, in time, atheroma. AGE-crosslink formation results in arterial stiffening with loss of elasticity of large vessels. This arterial stiffness has recently been shown to be reversed by the administration of another anti-AGE class of compounds called AGE-breakers.
Unfortunately we all have to worry about AGEs. AGEs is implicated in the process of aging and many diseases. Current evidence points to glucose, not only as the body’s main short-term energy source, but also as the long-term fuel of diabetes complications, mainly in the form of oxidative, pro-inflammatory AGEs. Foods high in sugar need to be avoided, and food commonly consumed after exposure to heat contains a significant amount of pre-formed AGEs, a fact that offers a new perspective on food as a major environmental risk factor.
Published studies have suggested that High fructose corn syrup decreases glucose tolerance, increases insulin resistance, and speeds up the process of glycation – contributing to complications of diabetes and aging. Sugar's major drawback is that it raises the insulin level, which inhibits the release of growth hormones, which in turn depresses the immune system. Harvard researchers recently reported that women who drank one or more sugar-sweetened soft drinks per day were 83% more likely to develop type 2 diabetes than women who drank less than one a month.