This study looked at the link between the progress of diabetes and peroxidative damage of body tissues in a population of almost 500 patients with NIDDM attending a diabetes centre in Madras, India. It had previously been noted that diabetes mellitus patients displayed an imbalance in their antioxidant protective mechanism, placing cells under oxygen stress. When that happens, dangerous oxygen-derived products such as free radicals are created that can damage DNA, deactivate enzymes, oxidize hormones, and harm membranes. All aerobic cells create the dangerous oxygen-derived products, most notably (and in ascending order of cell lethality) superoxide radical, hydrogen peroxide and hydroxyl radical. But the healthy body also contains “scavengers” known as antioxidants that hunt down these menacing free radicals and detoxify them.
This is the role of vitamins A, B-carotene, C and E, and a group of less well-known scavengers such as glutathione. Each of these scavengers has the ability to exist in oxidized and reduced form, which means they can take on oxygen atoms or shed them without becoming toxic. When they encounter a free radical such as hydroxyl radical (OH-), their ability to take on the extra oxygen detoxifies the hydroxyl radical and prevents it from dumping its oxygen elsewhere. If no scavenger finds the free radical, it will oxidize cellular lipids, proteins, or nucleic acids, causing cell tissue damage. People with diabetes are especially prone to the creation of such reactive oxygen products in the blood because of the auto-oxidation of glucose and glycosylated (glucose-bound) proteins.
Evidence of increased peroxidation was found in the 467 cases of NIDDM examined. The body contains certain substances that protect against peroxidation: Vitamin C (a potent antioxidant), glutathione (which protects red blood cells from oxidative stress and destruction), superoxide dismutase (an enzyme that regulates the transfer of oxygen atoms) and catalase (a blood protein that breaks peroxides up into harmless water and oxygen). Deficiencies in all of these vital protective substances were noted in the first two years after onset of NIDDM. Moreover, lipid peroxidation appeared to increase with the duration of NIDDM.
The question to be examined next is whether antioxidant deficiency is a cause — and not just a consequence — of diabetes. This can be done by analyzing the antioxidant levels in people susceptible to NIDDM, such as people who are obese and glucose intolerant or who have a family history of the disease. As well, researchers can evaluate treatments capable of increasing the antioxidant level in patients with NIDDM, which may help to control lipid peroxidation. This type of treatment could reduce some of the secondary complications of diabetes mellitus, most of which flow from the vascular and capillary damage done by unchecked oxidation.
Questions – Answers
1. Are there any treatments now available to raise antioxidant levels?
It is always possible to take supplements such as the scavenger vitamins A, C, and E. In fact, it is normal for such antioxidant supplements to be given to antioxidant-deficient diabetics. But that does not necessarily mean that the patient’s levels of antioxidant enzymes such as glutathione will rise. There is no drug treatment that can ensure that. However, high levels of antioxidant vitamins will partly compensate for low levels of antioxidant enzymes.
2. What exactly is peroxidation, in simple terms?
Oxidation is what we call the process of combination between oxygen, created naturally in all aerobic cells, and a molecule, in which oxygen atoms are transferred to the new molecule to create an oxidized form. Peroxidation occurs when the molecule is loaded with the maximum number of oxygen atoms it can handle. This molecule then becomes a reactive and unstable free radical, and will shed its extra oxygen on cellular lipids, proteins and so on. Normally, the body prevents this by scavenging free radicals and stripping them of their toxic extra oxygen. People who are deficient in antioxidants, including many diabetics, are unable to scavenge all of the free radicals in circulation and suffer oxidative tissue damage.
3. Do people with NIDDM seem to be more at risk from oxidative stress because they have more oxygen free radicals, or because they have fewer antioxidants?
Studies suggest that people with both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes, on average, have cells that produce toxic oxygen by-products such as peroxides in larger quantities than other people. They also seem to suffer more tissue damage due to oxidation. So it may be that diabetics have more free radicals, fewer antioxidants, and the free radicals do more harm than in other people. This is certainly one of the main mechanisms linking diabetes to cardiovascular complications, though I would hesitate to say it is the most important.