IF YOU HAVE DIABETES, you probably spend plenty of time thinking, talking, and worrying about blood glucose. Keeping it under control through diet, exercise, and medication can feel like a full-time job. It may seem odd that such a small, sweet thing can be such a big bother.

Ever wonder what it is about high blood glucose that leads to the serious complications of diabetes? So have scientists. They think the key link may be molecules known as advanced glycation end products, or AGEs. As blood glucose rises, these substances increase in the body, and when too many AGEs accumulate, they may be hazardous to your health. The evidence is not all in yet, but here’s a peek at what research has shown so far.

The AGE-ing Process
As the concentration of glucose in the blood increases, there’s a shift in the body’s chemical balance that allows glucose to attach to other molecules, often vital proteins that, for example, make up body structures like blood vessels. And when glucose coats proteins like a sickly sweet glaze, an AGE is created. AGEs can damage proteins “in very important ways that contribute to cell dysfunction and the complications of diabetes,” says Paul Thornalley, PhD, a professor at Warwick Medical School in England.

AGEs are apparently regarded by the body as cellular junk; normally, the body takes out the trash. Yet in people with diabetes, the sheer number of AGEs may overwhelm the system for clearing them out of the body. “We are producing these [AGEs] all the time, even those without diabetes, but most people excrete the AGEs in their urine. But a person with diabetes may have 10 times as much in their urine,” says Thornalley.

The buildup of AGEs is likely to cause damage that leads to complications in people with diabetes. Researchers aren’t sure how this happens, but they are focusing on the one thing all diabetes complications have in common: damage to blood vessels.  Tiny blood vessels in the eye can swell and leak, leading to retinopathy. Injured blood vessels in the kidney can cause its delicate filters to thicken and become less adept, resulting in nephropathy. When blood vessels that supply nutrients and oxygen to nerves become affected, neuropathy can result. And lesions on blood vessel walls cause atherosclerosis, which raises the risk of heart attack and stroke.

The evidence that AGEs are a link among complications is scattered but compelling. Researchers have found heavy AGE buildup in organs of the body that are prone to diabetes-related injury: the kidneys, eyes, and nerves. In one study, the level of AGEs in the eyes of people with type 2 diabetes was found to correlate with the severity of retinopathy. AGEs may be linked to cardiovascular disease, too. The lining of the blood vessels becomes stiffer as AGEs accumulate; stiff blood vessels are a cause of high blood pressure. AGEs may also interfere with the body’s natural mechanism for removing LDL (“bad”) cholesterol. And there’s evidence that AGEs increase blood vessel inflammation, which is believed to be a central factor in heart disease.

Collagen, a protein in the body, provides an example of how AGEs can affect blood vessels. This chain-like protein is like a scaffold for the cells that make up the blood vessels. “If collagen becomes glycated by an AGE, it is damaged at the site where the cell binds to this protein,” says Thornalley. “The cells become detached and float around in the blood and die. This leaves a gap in the vessel wall and can cause thrombosis [blood clot formation], which down the line can trigger heart disease or stroke.”

Next: The food connection