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Research Newsletter-Spring/Summer 2007

Diabetes

An interview with Tammy Bray, Ph.D.
Dean, College of Health and Human Sciences, Oregon State University
LPI Principal Investigator

Q. What causes diabetes?

A. There are two kinds of diabetes—Type 1 and Type 2. Juvenile diabetes, or Type 1, usually begins at an early age and is associated with an acute infection. Type 2 diabetes, or adult-onset diabetes, begins later in life and is associated with diet and lifestyle.

Q. How prevalent is diabetes?

A. Type 1 accounts for between five and ten percent of the diabetes cases, which in total number over 20 million in the U.S. Type 1 is almost like a viral disease, and its incidence is pretty similar in all countries. Type 2 has had a dramatic increase of 80-85% in recent years. Type 2 is preventable. Its prevalence in Western societies increases proportionally with body weight and the BMI (body mass index).

Q. Is ethnicity or gender related to diabetes risk?

A. Those characteristics don't affect risk for Type 1 diabetes, but Hispanics and Blacks are more likely to develop Type 2 diabetes, and the risk for men is greater than for women. If youíre prone to obesity, you're more prone to Type 2 diabetes. From an evolutionary perspective, those with thrifty or frugal genes who now eat too much or don't get enough exercise are at risk for Type 2 diabetes. There is a genetic predisposition for Type 2 diabetes, but not for Type 1. When humans were mainly hunters and gatherers, the genetic program favored storing energy because food might not be constantly available. Now, in Western societies we have an abundance of food, and overconsumption leads to energy storage as fat.

Q. Is oxidative stress implicated in the development of diabetes and, if so, why?

A. For Type 1 diabetes, definitely yes. The cause of the disease is multi-factorial and immunity plays a role. Curiously, Type 1 diabetes is often precipitated by an infection like influenza. Thereís something that triggers the infection and inflammation. The pancreas, the organ that produces insulin, may become inflamed and insulin-producing cells, called beta cells, then die, partly as a result of oxidative stress.

Q. Why is the pancreas, in particular, affected by the infection?

A. Some organs are more sensitive to inflammation and oxidative stress. The liver and the lung probably have stronger defense systems. The pancreas, and beta cells in particular, have comparatively less protection. When you get an infection like the flu, free radicals are generated that attack the pathogens and vulnerable cells. Unfortunately, beta cells in the pancreas are very vulnerable to free radical damage.

Q. Why are juveniles at risk for developing diabetes as a result of an infection, whereas adults are not?

A. In young people, the defense system is immature, as measured by substances that protect against oxidative damage, such as superoxide dismutase, glutathione peroxidase, glutathione, and catalase. Older people have higher levels of these protective molecules, so they are less vulnerable.

Q. Is there any evidence that good antioxidant status—low oxidative stress—protects against diabetes in children? Has this been studied in animal models?

A. We haven't done any epidemiological studies, but we did an intervention study with animals. While not all viral infections induce diabetes, some chemicals similar to glucose, such as alloxan, can be used to induce diabetes. Alloxan is very specifically picked up by beta cells in the pancreas and then kills them, stopping the production of insulin. So you prepare the animals when they're young by giving them lots of antioxidants—vitamins E and C, glutathione, or N-acetylcysteine, a precursor of glutathione. Animals that have been fed these antioxidants and then challenged with alloxan are more resistant to Type 1 diabetes. This may be relevant to humans—children with good antioxidant status may be less vulnerable to Type 1 diabetes, but we don't have studies yet to support that.

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Q. Why does exercise lower the risk of diabetes?

A. We know that exercise, for whatever reason, makes the receptor for insulin much more sensitive. If you measure insulin in someone who exercises a lot, the concentration is low compared to a sedentary or less active person. When this was observed in the late 1970s, investigators thought something was wrong. They found out that we donít need a lot of insulin. Insulin produced by the pancreas allows muscle to take up the blood glucose after a meal. In very athletic people, the insulin sensitivity is very efficient, so they don't need a lot. In an obese person, more insulin is produced, and it takes more to get the muscle to take up glucose. So the insulin sensitivity is blunted and less efficient. When you have Type 2 diabetes for a long time, there's a drop in insulin production, probably because the pancreas has deteriorated. For whatever reason, physical activity prepares you for high sensitivity of insulin and its cellular receptor. That's why it's important to keep active. When someone first gets diagnosed with Type 2 diabetes, my advice is to avoid sugar and to walk. Even starting with a small amount of walking is very beneficial.

Q. How much exercise do you recommend for people who have just been diagnosed with Type 2 diabetes?

A. About 30 minutes of exercise a day is for health maintenance. That increases your insulin sensitivity. You can start with ten minutes a day and increase to 20 minutes a day, then to 30 minutes. That may not change your body weight, but you will have a lot of health index changes, like sensitivity to insulin and improved blood lipid profile. Sixty minutes of exercise three times a week is probably best, but if you want to lose weight you have to get 90 minutes and reduce your caloric intake. Exercise also induces antioxidant defense systems. Superoxide dismutase and glutathione peroxidase increase. Exercise may not dramatically reduce your body mass index, but it will increase your health span and improve your quality of life.

Q. What is the relationship between insulin and blood sugar and why is chronically elevated blood sugar harmful?

A. Your body needs energy. The energy that's needed comes from glucose. After a meal, your digestive system converts all the carbohydrates into glucose. The glucose from the carbohydrates you eat has to be absorbed by the muscle and produce energy. Something has to allow the glucose to get into the muscle. Insulin fits into the insulin receptor on cells and permits the glucose in the blood to get into the muscle. Muscle will take it up and store whatever it needs later as glycogen, or burn the fuel in mitochondria to produce chemical energy. In diabetes, the insulin receptor mechanism doesnít work very well, so glucose increases in the blood. Some glucose gets filtered out in the kidney and shows up in urine. This was first observed in dogs without a pancreas. Flies swarmed to their urine because it contained so much glucose.

Q. So now the glucose is going into the urine instead of the muscle.

A. Yes, and that causes a lack of energy. Insulin and glycogen maintain the blood glucose level. When the glucose level becomes too high, it causes the vasculature to become rigid, which increases the risk of heart disease. This process is based on the Maillard reaction, in which advanced glycation end products (AGE) are generated. AGE are toxic and contribute to the risk of heart attacks and other diseases.

Q. What happens when the vasculature becomes rigid?

A. Circulation, especially in the capillaries, becomes impaired. That's why wounds are dangerous in diabetes—the capillaries don't eliminate toxins, raising the risk for tissue damage and amputation of the extremities. The eye is also very sensitive to impaired blood flow. Vascular rigidity is also linked to high blood pressure.

Q. What dietary interventions are helpful in managing diabetes?

A. It helps to eat complex carbohydrates, whole grain products, and fiber in fruits and vegetables. Don't eat simple carbohydrates like sugar or highly processed foods. It takes time to gradually digest and absorb complex carbohydrates or whole grain foods, so your body's reaction to insulin is appropriate. It's not a surge. Simple and processed sugars are readily absorbed in the blood, causing a quicker insulin reaction. If your insulin response doesn't work well, sugar cannot get into the muscle, so you have a high concentration of glucose in the blood.

Q. Is that the basis for the glycemic index of foods?

A. Yes. Glycemic index compares the rise in blood sugar after eating a food to the rise after consuming glucose or white bread.

Q. Can Type 2 diabetes be cured by following dietary recommendations?

A. It can't really be cured, only managed. Over time, the sensitivity of your insulin receptors may increase, but it's critical to manage the disease so that you don't have high blood glucose and the vascular problems that affect the eyes, the feet, and the fingertips.

Q. Are antioxidant supplements like vitamin C, vitamin E, and lipoic acid helpful in managing diabetes?

A. Oxidative stress is associated with diabetes. Lipoic acid has been used to treat diabetic neuropathy, which results from impaired capillary blood flow to the neurons. Lipoic acid also plays a role in energy and protein metabolism. I think that diet and exercise are most important.

Q. Is zinc useful in treating diabetes?

A. I tested zinc. Zinc is an antioxidant, but it also dampens the activity of the immune system, and too much may be toxic. If your baby has a diaper rash you put on zinc oxide to help. But zinc oxide doesn't cure diaper rash; it prevents the damage of the infection.

Q. What about chromium?

A. It's important to maintain a good chromium status and prevent deficiency, but I'm not sure that supplementation helps much in diabetes.

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Q. Are there any specific foods or beverages that seem to be linked with an increased risk for Type 2 diabetes?

A. Don't drink soda pop with sugar. It's better to eat fruit than drink fruit juice. Tomato juice is a better choice—low calorie, more fiber, less sugar, and low glycemic index.

Q. Are sucrose substitutes acceptable for diabetics?

A. Fructose is not better because it is converted to glucose in the body. One artificial sweetener is made of hydroxylated phenylalanine. People with PKU can't use that. If you have to use a sweetener, artificial sugar substitutes are okay for most people.

Q. Why have you studied wound healing?

A. It seems that so many things are involved—nutrient deficiencies, oxidative stress, and immune function. In diabetics, wound healing is impaired and, as I mentioned, may lead to amputation. The immune system is affected by stress, and that can also cause delayed wound healing. The first stage of wound healing is the blood clot. Of course, if clotting is impaired, you continue to bleed. Too much clotting is also dangerous—it may cause a heart attack or stroke if the clot migrates to other organs. The immune system responds when we have a wound by producing inflammation, which does two things. One, it kills the bacteria at the wound site. It also sends out a signal for cells to grow—to proliferate. The inflammation stage is important, but after these effects have occurred, it needs to subside. Zinc is important for that, as are many other substances. When the inflammation subsides, the next signal triggers proliferation. This produces cells that repair the wound. Then you want the proliferation stopped. Once the new cells add to the skin or some other tissue that's been damaged, the process should stop. If it doesn't, you may have uncontrolled proliferation or cancer.

Q. What happens in diabetes that impairs this process?

A. Chronic inflammation is to blame. Inflammation is also linked to prostate cancer. I studied hormonal-induced inflammation, which is involved in prostate cancer. The whole process is just like wound healing except it's much longer. You have a cut on your skin and in a few days new epithelial cells have replaced the wound. If you don't allow the wound to heal, it can become cancerous because the cells keep proliferating. In the prostate, abnormally high hormone levels contribute to the risk of cancer because they are inflammatory.

Q. How do you study this?

A. In animals, we can increase testosterone, which increases the incidence of prostate cancer by about 70%. If you also increase estrogen, the incidence increases to 100%. Our hypothesis is that high levels of hormones activate inflammatory molecules like NFkappaB. The prolonged activation of these molecules causes cell proliferation.

Q. How is zinc status related to prostate cancer risk?

A. Zinc is normally found in high concentrations in the prostate and in seminal fluid. We don't know why, but we are working to find out. Zinc deficiency may be a risk factor for prostate cancer.

Q. Epidemiological studies have found associations between the consumption of tomato products and decreased incidence of prostate cancer. Which phytochemicals in tomatoes might be responsible for this protective effect?

A. The most popular theory right now is that a carotenoid called lycopene is protective. Other carotenoids may be protective, too. In rats, lycopene is effective in reducing hormone- or carcinogen-induced prostate cancer, but it's not as effective as the whole tomato or freeze-dried tomato powder. Lycopene accumulates in the prostate. It is fat soluble, so the recommendation has generally been to consume tomato products with a little oil to improve absorption.

Q. Is there any difference in lycopene bioavailability between cooked or raw tomato products?

A. Lycopene in processed tomato products is more bioavailable, but consumption of any tomato product is probably beneficial.

Q. What nutritional or lifestyle modifications do you recommend to decrease the risk for prostate cancer?

A. Levels of prostate-specific antigen, or PSA, are used to monitor prostate cancer risk. If you put men with very high PSA levels on a low-fat anticancer diet that includes tomato products, vegetables, and fruit, like the Mediterranean diet, and also increase their exercise level, they lose weight and their PSA levels drop. If they stop the diet and exercise, their PSA levels go up.

Q. In addition to conducting research, you are Dean of the College of Health and Human Sciences. What activities do you encourage in the College?

A. Well, collaboration is my philosophy and guiding principle. I think people shouldnít do anything in isolation. Collaboration is not simply doing things together; it means solving problems in multiple ways. Different scientists have different perspectives. When we collaborate, there is synergy and the whole becomes much more than the sum of the parts. So I am motivated to bring faculty together. I want to help the junior faculty in my college to be successful, help them to write grants and collaborate.

Last updated May 2007