The Significance of Diabetes, Part 3
Most diabetologists believed that diabetic complications are caused by the toxic effects of high blood sugar, despite the fact that this view cannot explain why atherosclerosis has remained relatively impervious to insulin therapy. Unfortunately, the carbohydrate hypothesis is only being pursued in a few laboratories. As a result, its ultimate implications and validity remain to be ascertained. However, it should be considered another potential mechanism by which consumption of refined carbohydrates could cause or exacerbate the entire spectrum of the chronic diseases of civilization.
Raising blood sugar will increase production of reactive oxygen species and glycation end-products which are particularly toxic. Reactive oxygen species get generated when the cells burn glucose for fuel in the cells (so much for glucose being the body’s preferred fuel), in a process that attaches electrons to oxygen atoms, transforming the oxygen from a relatively inert molecule into one that is avid to react chemically with other molecules.
One form of reactive oxygen species is those known commonly as free radicals and all of them together are known as oxidants because they oxidize other molecules much like rust oxidizes metals. Neither of which is good! The resulting deterioration is known as “oxidative stress.” Antioxidants neutralize reactive oxygen species which is why they have become such a popular buzz word in nutrition discussions. Seems to me that if we eat less of that which produces oxidants….
The potential of advanced glycation end-products or AGEs is equally bad as reactive oxygen species. They take years to form but the process starts simply. A glucose molecule attaches to a protein without the benefit of an enzyme to orchestrate the reaction. Enzymes ensure that chemical reactions “conform to a regulated metabolic program” as Harvard biochemist Frank Bunn explained.
“Enzymes affix sugars to proteins at particular sites on proteins. Without an enzyme overseeing the process, the sugar sticks haphazardly to the protein and provides for more unintended and unregulated chemical reactions.”
Glycation refers to this initial step and this is reversible, if blood sugar levels are low enough. This will cause the sugar and protein to disengage and no damage will be done. If blood sugar remains elevated, glycation will continue and the AGEs will bond with other AGEs, effectively bonding more proteins in a process called “cross-linking.” This inexorably binds proteins that should ideally have nothing to do with each other.
Since the mid-1970s Rockefeller University biochemist Anthony Cerami and Frank Bunn recognized that AGEs and glycation play a major role in diabetes. They observed that diabetics have an unusual form of hemoglobin, the oxygen-carrying protein of red blood cells, known as hemoglobin A1C. The higher the blood sugar, the more A1C is found in the blood circulation. They found that diabetics have two to three times as much hemoglobin A1C as non-diabetics, a ratio that apparently holds true for all glycated proteins in the body. Diabetics know that the A1C level reflects the average blood sugar level over a month or more and is a sure sign as to whether the diabetic condition is being controlled or not.
AGEs have also been linked to aging, hence the acronym. They accumulate in the lens, cornea, and retina of the eye where they appear to cause the browning and opacity of the lens characteristic of cataracts. They also accumulate in the kidney membranes, nerve endings, and in the lining of the arteries, all tissues typically damaged in diabetic complications. Because AGE accumulation appears to be a naturally occurring process, although it is exacerbated and accelerated by high blood sugar, we have evolved sophisticated defense mechanisms to recognize, capture, and dispose of AGEs. However, AGEs still manage to accumulate with age, especially in diabetics.
Collagen is particularly susceptible to glycation and cross-linking. It is a fundamental component of bones, cartilage, tendons, and skin. This is why the skin of diabetics will appear prematurely old, and why, as Case Western University pathologist Robert Kohn suggested, diabetes can be thought of as a form of accelerated aging. This is also responsible for loss of elasticity in the skin with age, as well as in joints, arteries and the heart and lungs. The bottom line is all these things are caused by sugars reacting with proteins. If one were to take the heart of one who died young, they could blow it up like a balloon and also remove air to deflate the heart. However, blowing air into the heart of an older person would be equivalent to blowing air into a metal pipe, it simply would not expand.
AGEs and the glycation process play a direct role in heart disease by causing the oxidation of LDL and its accompanying cholesterol to become trapped in the artery wall, which is an early step of atherosclerosis. Oxidized LDL appears to be resistant to removal from the circulation by the normal mechanisms.
It turns out that LDL is particularly susceptible to oxidation by reactive oxygen species and glycation. There’s also evidence that HDL molecules can become glycated, inhibiting their function and rendering the HDL more pro-atherogenic. Of course, these LDL particles appear to be markedly elevated in both diabetics and non-diabetics with atherosclerosis and they’re likely to be found in the atherosclerotic lesions themselves.
Recent experiments on animals with compounds known as anti-AGE or AGE breakers have successfully reversed arterial stiffness in laboratory animals and is reported to ameliorate the “adverse cardiovascular and kidney related changes associated with aging, diabetes and hypertension.” Whether these or similar compounds will work in humans remains to be seen.
This all means that anything that raises blood sugar, by the logic of the carbohydrate hypothesis, will lead to more atherosclerosis and heart disease, more vascular disorders, and an accelerated pace of physical degeneration even in those who never become diabetic!
Share on TwitterOne Response
Subscribe to comments via RSS
Subscribe to comments via RSS
Leave a Reply
You must be logged in to post a comment.
on February 13, 2009 at 10:46 pm
Permalink
[...] The Significance of Diabetes Diabetics know that the A1C level reflects the average blood sugar level over a month or more and is a sure sign as to whether the diabetic condition is being controlled or not. AGEs have also been linked to aging, hence the acronym. [...]