Approximately 18.2 million Americans have diabetes. A great majority of these patients (90% to 95%) have Type 2 Diabetes (T2D), and this number is exploding due to increasing rates of obesity and other lifestyle risk factors. Diabetes is a very serious disease that results in approximately 450,000 deaths a year. These deaths usually are a result of the devastating complications from diabetes, which in effect causes damage to almost all major organ systems. The total direct and indirect costs from diabetes are $132 billion per year; that is approximately $562 for each American.
T2D is a disease in which glucose, the fuel for the body, cannot be properly regulated. It often starts as insulin resistance, a problem in which the tissues do not adequately respond to insulin whose role is to shift glucose into cells for utilization and storage. This unresponsiveness to insulin results in high blood glucose. Over time the insulin producing cells of the pancreas are destroyed, thus causing worsening glucose control. Obesity is a significant risk factor for insulin resistance and T2D. Other risk factors such as diet and physical activity can have an impact on the development and progression of T2D.
Diabetic Complications
The harm to patients with T2D is much greater than the nuisance of having to measure their blood glucose and take medications and/or insulin on a daily basis. High blood glucose results in a cascade of events that result in damage to organ systems including the vessels—the arteries and veins of the body. Microvascular complications affect small arteries and include neuropathy (nerve damage), nephropathy (kidney damage) and retinopathy (retina damage). These complications are common as diabetic retinopathy, a leading cause of blindness, affects 75% of diabetics who have the disease for more than 15 years. Macrovascular complications, including cardiovascular disease and stroke, cause about 65% of the deaths related to diabetes.
Preventing, Delaying T2D
How do we prevent or delay T2D, on an individual basis and on a societal level, in hopes of avoiding the devastating complications of T2D, the cost to society, and the reduction in quality of life? The answers, unfortunately, while simple are difficult to implement.
As mentioned above, obesity, diet and exercise are significant risk factors for T2D. Clinical trials have proven that weight reduction and lifestyle modification can reduce the incidence of diabetes up to 58% in high-risk patients (Diabetes Prevention Program). Despite the simplicity and effectiveness of this solution, it is difficult to get people to change their habits.
Others have tried pharmaceuticals to aid in the prevention of diabetes. Clinical trials using metformin and acarbose, drugs used to treat diabetes, have also shown significant reduction in the progression to diabetes among high-risk persons. However, the risk reduction achieved with these drugs—31% for metformin and 25% for acarbose—are smaller when compared to the effectiveness of lifestyle modification.
Understanding the pathophysiology of T2D can assist researchers in developing new weapons to fight this disease. While we still do not understand the root cause of diabetes, scientists are slowly unraveling some of the details, on a molecular level, that result in the initiation and progression of the disease.
Increasing evidence from both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes. Oxidation is the process in which apples turn brown and rust forms on metal. Free radicals, molecules with unpaired electrons, cause oxidative stress by stealing electrons from other molecules. This process, also called oxidative stress, can damage your cell membrane, proteins, enzymes and even DNA.
Free radicals are disproportionately formed in diabetics due to several factors, including high blood glucose. In the pancreas, abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can cause cell death, thus decreasing the number of insulin-producing cells.
The use of antioxidants in the prevention or delay of T2D has not been thoroughly studied in humans. Studies in mice have shown that antioxidants, such as vitamin E, may delay the incidence and onset of T2D. A study in humans did find that higher blood levels of vitamin E were protective against T2D. More research is needed.
Preventing, Delaying Complications
Free radicals and oxidative stress not only are implicated in the causative pathway of diabetes but also are intimately responsible for causing diabetes-related complications. Evidence from both in vitro and in vivo studies indicates that diabetic stresses including high blood glucose, glucose formed byproducts and elevated free fatty acids, increase the oxidative stress in different cell types. The mechanism of cell damage includes direct toxicity and cell signaling mediated transformations that result in severe damage and or death.
If oxidative stress and free radicals have a role in increasing the risk of diabetes and its complications, can antioxidants be beneficial? The answer is yes, and the basic science and clinical research to support this answer is increasing.
For example, investigators have found that antioxidants such as ascorbic acid, lipoic acid and alpha-tocopherol have a protective effect against the death of retinal cells. Others have found that vascular, nerve and kidney cells are also protected by certain antioxidants.
Clinical studies have shown that antioxidants can be very effective in reducing diabetic complications. One of the most studied antioxidants in diabetic neuropathy, the disabling loss of sensation and pain most commonly in the extremities (arms and legs), can be reduced by alpha lipoic acid. The ALADIN Trials have investigated the use of alpha-lipoic acid in diabetic neuropathy. In ALADIN I, a multicenter, randomized, double-blind study showed that an intravenous administration of alpha lipoic acid over 19 days reduced symptoms of burning, pain, paresthesia, and numbness in diabetic patients with peripheral neuropathy. Similar results were found in the Sidney Trial with intravenous alpha lipoic acid but oral alpha lipoic results in ALADIN II and III have been mixed in contrast to the OPRIL study that showed significant benefit. Further studies are under way. The oral dosages used in these studies range from 600 mg to 1,800 mg per day.
In a preliminary double-blind randomized placebo-controlled study in 21 patients with diabetic neuropathy, patients receiving 900 mg of vitamin E had improvements in median and tibial motor nerve conduction velocity. The other members of the vitamin E family, although not evaluated in clinical studies may be beneficial due to their unique antioxidant and non-antioxidant properties. These include gamma-tocopherol because of its ability to scavenge nitrogen free radicals. Peroxynitrite, and its metabolite, nitrotyrosine, are nitrogen free radicals that are elevated in T2D and toxic to vascular and other cell types.
Other antioxidants that have not been evaluated in clinical studies but have shown promise in basic science research include Coenzyme Q10. Coenzyme Q10, like alpha lipoic acid, can inhibit lipid peroxidation in mitochondria. Coenzyme Q-10 is also involved in the regeneration of other antioxidants such as alpha-tocopherol and ascorbic acid. Diabetics are known to have low plasma or serum Coenzyme Q10, and, more important, low ubiquinol, the reduced form of Coenzyme Q10.
Omega-3 fatty acids (found in fish and fish oil supplements) are showing promise for reducing the increased risk of cardiovascular complications and neuropathy in diabetics. Clinical studies evaluating other compounds such as acetyl-L-carnitine, pyridoxine and evening primrose oil are negative or inconclusive. Evidence for herbal remedies such as ginseng, bitter melon and bilberry are beyond the scope of this article.
Suggestions
Persons who are at high risk for diabetes should consider making appropriate lifestyle changes such as maintaining a healthy weight, eating a healthy diet and exercising. In addition, a wide spectrum antioxidant with additional vitamin E may be beneficial.
- A basic wide-spectrum antioxidant should include alpha-lipoic acid, Coenzyme Q-10, natural carotenoids (alpha-, beta- and gamma-carotene, lutein, lycopene and astaxanthin), vitamins A, C and E, selenium, zinc, copper and manganese and B vitamins, including B-6, B-12 and folic acid.
- A vitamin E product should supply 400 IU plus 400 mg of the other tocopherols and tocotrienols.
Persons with diabetes who hope to minimize the onset of complications should first aggressively maintain normal glucose levels with the help of their physicians. In addition, the lifestyle factors mentioned above can be very helpful in reducing insulin resistance and maintaining a normal glucose level. Finally, antioxidants such as alpha-lipoic acid and vitamin E have been shown to provide benefit. A regimen should include the advice given above of a wide-spectrum antioxidant with the full family of vitamin E with the following additional supplementd vitamin E
- A vitamin E product high gamma tocopherol supplying approximately 450-500 mg gamma tocopherol)
- An omega 3 supplement that provides approximately 420 mg EPA (eicosapentaenoic acid) and 280 mg DHA (docosahexaenoic acid) in combination with mixed tocopherols (high in gamma tocopherol) to maintain freshness.
References available on request from the author; send an e-mail to apapas@yasoo.com.
