The Diabetes Damage Cascade
Glycation and oxidative stress are central to the damage caused by diabetes. Unfortunately, neither of them figures into conventional treatment for diabetes, which is generally concerned only with blood sugar control.
Glycation occurs when glucose reacts with protein, resulting in sugar-damaged proteins called advanced glycation end products (AGEs) (Kohn 1984; Monnier 1984). One well-known AGE among diabetics is glycated hemoglobin (HbA1c). HbA1c is created when glucose molecules bind to hemoglobin in the blood. Measuring HbA1c in the blood can help determine the overall exposure of hemoglobin to glucose, which yields a picture of long-term blood glucose control.
Glycated proteins damage cells in numerous ways, including impairing cellular function, which induces the production of inflammatory cytokines (Wright 2006) and free radicals (Forbes 2003; Schmidt 2000). In animal studies, inhibiting glycation protects against damage to the kidney, nerves, and eyes (Forbes 2003; Sakurai 2003). In a large human trial, each 1 percent reduction in HbA1c correlated with a 21 percent reduction in risk for any complication of diabetes, a 21 percent reduction in deaths related to diabetes, a 14 percent reduction in heart attack, and a 37 percent reduction in microvascular complications (Stratton 2000).
High levels of blood glucose and glycation also produce free radicals that further damage cellular proteins (Vincent 2005) and reduce nitric oxide levels. Nitric oxide is a potent vasodilator that helps keep arteries relaxed and wide open. Oxidative stress in diabetes is also linked to endothelial dysfunction, the process that characterizes atherosclerotic heart disease. According to studies, diabetes encourages white blood cells to stick to the endothelium (i.e., the thin layer of cells that line the inside of arteries). These white blood cells cause the local release of pro-inflammatory chemicals that damage the endothelium, accelerating atherosclerosis (Lum 2001). Diabetes is closely associated with severe coronary heart disease and increased risk of heart attack.