Dia-Besity Overtakes America

Patrick Perry

The swelling ranks of overweight Americans parallel an equally dramatic increase in type 2 diabetes. There are ways to help ward off the onset and complications of the chronic disease.

For 41-year-old Frank Papsadore, the diagnosis of type 2 diabetes was a long-overdue wake-up call. During the preceding ten years, the Boston native had steadily packed on 150 pounds, and the weight was exacting a toll. He began feeling lousy at work and experiencing dizzy spells. A trip to his physician revealed a fasting blood sugar level over 400, well above the normal range of 70 to 110. Frank was immediately started on medication.

“It was a real shock both physically and emotionally,” Frank says. “I had never been sick in my life. No one in my family had diabetes.”

Frank’s lifestyle had caught up with him. Huge late-night dinners and little or no exercise placed him at high risk for type 2 diabetes.

Joining 16 million other Americans, Frank became another statistic in what health experts are calling an epidemic of type 2 diabetes in the United States.

Fortunately, Frank faced the problem head-on by researching exercise and diet programs in his area. He discovered that the Joslin Diabetes Center in Boston was recruiting volunteers for a research study, investigating the impact of lifestyle changes on diabetes control. After enrolling in the study, Frank began incorporating long walks into his daily routine and improved his diet with the help of a knowledgeable chef. Today, Frank has lost weight (and the diabetes medications) and gained energy.

“There are many miles to go before I rest,” says Frank, “but I’m definitely going in the right direction.” The sharp increase of type 2 diabetes among all age groups, including adolescents, has health experts worried that unless steps are taken to stem the parallel trend of obesity and type 2 diabetes in the United States, we are facing a major health problem in the upcoming decades.

“We are all gaining weight,” Dr. Frank Vinicor, director of the CDC’s diabetes program, said recently. “And we are all being less active, and that is what is accounting for this apparently chronic disease epidemic.”

In the second installment of our two-part series on the twin epidemics of diabetes and obesity in the United States, the Post continues its interview with Dr. C. Ronald Kahn, president of the Joslin Diabetes Center, about lifestyle changes that individuals can make to help prevent the disease and its many complications.

Q: Some studies have found that a high-fiber diet helps people with diabetes.

A: A high-fiber diet tends to have a beneficial effect on blood glucose levels. Fiber helps slow the absorption of carbohydrates from the intestine. After a meal, blood sugars would normally go up and then gradually come back down. In people with diabetes, you can blunt this excursion by adding fiber to the diet and by counting the total amount of carbohydrate in the meal and making sure this doesn’t exceed what your healthcare team recommends for each meal.

Q: Are fruits and vegetables an important part of a meal plan for a person with diabetes?

A: Generally for people with diabetes, we recommend that they limit–but not dramatically–the number of fruits that they eat to avoid adding a lot of simple sugars in their diet. Fruit can contain more grams of carbohydrate per serving than vegetables, for example. But again, what we urge people with diabetes to eat is a healthy diet that includes a variety of foods and to make sure the number of grams of carbohydate they eat at each meal is consistent with what their doctor recommends.

Q: What role does exercise play in the treatment and prevention of type 2 diabetes?

A: Exercise definitely plays a role. We strongly recommend exercise for every age group, even for older people with physical limitations such as obesity, as part of their general health regimen.

There is an ongoing study called the Diabetes Prevention Program that is looking at the impact of lifestyle–diet and aerobic exercise–on type 2 diabetes. It is hard to separate exercise from diet, but a couple of studies have done this in a very nice way. These studies looked at the likelihood of developing diabetes in populations, based on the amount of activity corrected for body weight. By doing this, they showed that the more active people who come from the same genetic background and who consumed the same diet develop diabetes at a significantly reduced rate.

Q: Many of our readers are older. Should diabetic complications such as foot ulcers be taken into account when exercising? Can you offer recommendations on footwear and foot care for people with diabetes who walk and do other aerobic activities?

A: In older populations, one should account for a number of factors with regard to exercise. First, find an exercise that is age-appropriate. Some older people can do any activity; others can’t. We really encourage patients to find an exercise that they can do regularly. Vigorous walking, riding a stationary bicycle, and other simple nonstrenuous exercises are good, but activities should be adjusted for the patient. If a patient is older with heart disease, for example, they need appropriate exercise advice so they don’t run the risk of angina or cardiac insufficiency from overexercising. Older people with diabetes may also have other medical problems that limit their activity. In each case, we try to match the best exercise to the individual.

People with diabetes are also susceptible to certain physical problems, such as neuropathy or loss of sensation in the feet, which can cause a problem in that if they exercise and injure themselves, they may not be aware of it. It is very important that they are aware of and practice good foot care. They should choose properly fitting shoes. After exercise, they should check their feet to look for evidence of injury that could lead to further problems.

Q: Is it more difficult for a person with diabetes to lose weight?

A: No, at least not for a diabetic without an intrinsic problem losing weight. Many people with diabetes complain that when they start aggressive treatment to bring their blood sugar levels under control they gain weight. Nothing about the treatment causes them to gain weight; the treatment brings blood sugars down. But as a result of treatment, they spill less sugar into their urine (or sometimes no sugar), so all calories stick with them. If you consider that one pound equals about 3,600 calories and people with diabetes lose about 400 calories a day in their urine, over nine days those calories are equivalent to about a pound of weight that you would have otherwise gained. Over time, that can add up.

Q: What percentage of people learn that they have diabetes only after developing complications such as heart disease, stroke, kidney disease, or vision problems?

A: In adults, about one half of diabetic cases are detected either because of the presence of mild diabetic symptoms or during routine physical and laboratory examinations in which something shows up in the blood test, for example.

Q: What are the commonly overlooked symptoms of diabetes?

A: The classic and most common symptoms are called the polys–polyuria, polydypsia, and polyphasia–excessive urination, excessive thirst, and excessive eating or hunger. These symptoms certainly occur when diabetes is out of control.

Another classic symptom is frequent urinary tract or vaginal infections, which are often markers of silent diabetes.

People who have a positive family history and are overweight should always be advised that they are probably at high risk for developing diabetes and need to be aware of the symptoms and checked for the disease, even if they are asymptomatic.

Q: In recent developments, Mitchell Lazar, director of the University of Pennsylvania’s Diabetes Center in Philadelphia, published a paper discussing the role of a hormone called resistin and its relationship to diabetes. Could you tell us about this research?

A: Let me put this new research in context, because that is a good way to think about it. Despite the fact that we know much about diabetes and talk about the roles of genetics and the environment in diabetes, there are some very fundamental things about the disease that we are still learning and do not yet know. These questions include what actually causes insulin resistance, what is the link of genetics to insulin resistance, and can we identify new targets for drugs that might be useful in treating diabetes? There is a great deal of exciting research going on relating to diabetes and obesity. Over the past few years, many developments in both fields are demonstrating great promise for potential therapeutics and diagnostics and greater insight into the disease.

The recent study by Lazar is a good example of this. In the study, he was looking for the mechanism by which one of the insulin-sensitizing drugs–a class called the thiazolidinediones, or TZDs–works. Using molecular genetic techniques, he discovered that TZDs appear to control the level of production of a hormone called resistin. This study suggests that one way TZDs work is to decrease the amount of resistin. Resistin, according to his model, is actually produced by fat cells and acts on other tissues to cause some of the insulin resistance. His study mainly showed that resistin is regulated by TZDs and that if you lowered the levels of resistin, you could improve insulin resistance.

Resistin is probably one of many players, because fat cells produce certain other things that can also cause insulin resistance. And besides fat cells, other tissues may contribute to insulin resistance. Over the next several years, the observation could lead to the development of completely new classes of drugs that might be helpful in the treatment of type 2 diabetes.

Q: Is there potential for a diagnostic assay in the near future?

A: Absolutely.

Q: How have genome research and discovery aided researchers in finding a cure and developing treatments for diabetes?

A: Two or three things will be helpful from the Genome Project. First, we still don’t know the genes that predispose individuals to type 2 diabetes. A better human genome map will be a useful tool in identifying these genes, as well as new targets for therapy. If you find genes that are linked to type 2 diabetes and you know a gene produces a certain protein or enzyme that may be deficient, you can attempt to figure out how to restore the normal level of that protein or enzyme.

Second, the human genome will help us find the genes behind type 2 diabetes and help us identify people truly at risk for the disease. We can then be more vigorous about the lifestyle modifications or pharmacologic therapy necessary to prevent the disease. If I could do a simple genetic test on ten people in the population, for example, I could say that two people are more likely to develop diabetes while the other eight are much less likely to (or will not) develop it. We can then focus our attention on those two people to help them do the things likely to prevent diabetes, rather than diluting our attention to the group of ten people where eight may never get it, anyway.

Genetic discovery will also give us a better understanding of how genes interact, which is important because type 2 diabetes, like most common diseases, is what we call polygenic. It is not a simple genetic defect, such as sickle cell anemia or other diseases where we know that one gene with one sequence abnormality causes the disease. In type 2 diabetes, there are probably many subtle alterations in the genome occurring on several spots that together add up to a risk of diabetes. With the genome map, we will begin to learn which spots play a role in diabetes and how they add up.

Q: Some patients respond to a particular medication while others don’t. Will knowing the complete genome of an individual open up prospects for developing medical treatments tailor-made for individual patients?

A: Yes, that is certainly the belief. If we really knew the genetic composition, we would know the most appropriate medications for certain forms of diabetes versus another, and we might also know which individual has the right genes to allow the maximum response.

Q: Epidemiological maps suggest that there is a greater prevalence of diabetes in the southern United States. Why?

A: That is tree for type 2 diabetes. The reason presumably is linked to the issue of obesity, which is more prevalent in southern states than in northern states.

Type 1 diabetes, on the other hand, has a somewhat different geographic distribution. It tends to be more prevalent in northern climes. In a sense, the further you get away from the equator, the more you see type 1 diabetes. Nobody knows why, although people have speculated that whatever triggers the autoimmune disease is somehow influenced to be more prevalent in the northern areas.

Q: It seems that autoimmune disease would take a very heavy toll on the body’s supply of nutrients. Do dietary supplements help the diabetic?

A: Some animal studies suggest chromium might play a role and that chromium supplementation can reduce the incidence of diabetes in certain animals. A study done in China did show a positive effect of chromium to reduce the prevalence of diabetes. But there has never been a study in the U.S. or any westernized country to show that.

Another nutritional micronutrient that has shown positive effect in animal models to treat diabetes is vanadium salt–vanadyl and vanadate, which are available in health-food stores. We have done work on that, showing that vanadate and vanadyl actually have a positive effect on blood sugar control in diabetic animal models of several types. When we have given it to humans, it has been much less effective. We did it for several weeks and didn’t find an effect. We were using some pretty subtle measures of insulin sensitivity. Some micronutrients that work in animals don’t necessarily have the same effect in humans, although we haven’t studied all of them systematically.

Other micronutrients, such as vitamin E, have been talked about a lot for development of vascular disease and vascular complications of diabetes. We are not sure yet whether vitamin E will be of benefit in diabetes.

Certain things have been shown effective, such as the idea of taking baby aspirin, which reduces the risk of heart attack substantially in everyone. That has held up through a lot of studies.

Q: Since diabetics are prone to cardiovascular disease, what dosage of aspirin should diabetics take to help prevent problems?

A: Because aspirin can cause GI bleeding and so forth, the general recommendation is one baby aspirin. I recommend for my patients and myself to use the enteric-coated aspirin even if you don’t have a problem with your stomach, in part because it also slows the absorption and gives you a little better effect.

Q: When the islet cell breakthrough was first announced, we spoke with Canadian researchers at the Clinical Islet Transplant Program, launched at the University of Alberta in Edmonton, who had great success in treating patients with type 1 diabetes. This has been a phenomenal breakthrough for patients with type 1 diabetes.

A: Yes, it has been very important. We are one of the centers participating in the U.S. in the trials. The centers in the U.S. are focusing on making sure that when we do the islet transplant, we have the same quality of islet preparations used for the Canadian study. In the Boston area, there is a consortium of Harvard-affiliated hospitals and centers, including Joslin, doing islet cell transplant. The Joslin Center is the major center doing the islet isolation and preparation for this study.

Q: Will this discovery for type 1 diabetes eventually lead to developments in the treatment of type 2 diabetes?

A: I actually do not think that it will be applied to type 2 for two reasons. First, patients with type 2 diabetes are insulin resistant, unlike type 1 patients. This means that if you do islet transplantation in these patients, you would have to transplant even more islets.

Second, the major limitation in doing this procedure in type 1 patients is the number of islets available. Right now in the United States, about 3,000 pancreases are harvested per year for transplantation purposes. The Edmonton Protocol used on average two donors per recipient, or at least more than one. Therefore, even if you had one donor per recipient and could retrieve all islets out of them, we would only have enough islets for 3,000 transplants per year. In the United States alone now, there are about 30,000 new cases of type 1 diabetes per year. If islet transplantation proves to be as successful in the U.S. as in Edmonton; it is very clear that the amount of islet material cannot satisfy even 10 percent of the new patients developing diabetes. And that’s not even taking into account the million or so people who already have the disease. One of the biggest challenges is to figure out ways to harvest more islets for transplantation.

Q: Is Joslin participating in any clinical trials on the disease? Are there any that our readers may be interested in exploring?

A: There are quite a few. Our Web site (www.joslin.org) lists the open studies for both type 1 and type 2 diabetes, as well as for people with various complications.

Q: Briefly, what can people do to help prevent, or at least lessen the risk of developing, type 2 diabetes?

A: Stay thin! If you are not, get thin. I will highlight this by making one point. We did an ongoing study at Joslin for many years that investigated the development of diabetes in children where both parents had type 2 diabetes. In this population, there is a very high genetic risk for developing diabetes.

We followed them for over 25 years.

Of those who were overweight, 50 percent developed diabetes during the follow -up.

Q: Any there any new developments or treatments down the line that we should know about?

A: Over the past five or six years, there has been much more activity in developing new drugs for diabetes. Several new oral agents for type 2 diabetes are now available–the TZDs and a new class of agents that stimulate insulin release. In the area of type 1 diabetes, there are not only more purified insulins, but also genetically engineered insulins that have a better profile of activity.

For the first time in several decades, we are beginning to see some real new drugs for diabetes. I think that there are going to be quite a few more down the pipeline.

Q: There seems to be a mix of sad and hopeful news on diabetes. While many avenues are opening up, the incidence and prevalence are also escalating. Do you think that with this new information, we are zeroing in on a time that we might have a cure?

A: I am optimistic that within a decade, we are going to have some options for prevention of type 1 diabetes. We certainly have very good markers of who is likely to get the disease, and a lot of interest in trials for prevention.

I am a little less optimistic about whether we will have a cure, however. Islet transplantation may be appropriate for some individuals, but because of the limitations of islet tissue and the long-term risks of immunosuppression–which will be hard to eliminate completely–I am not sure that we will be able to cure these people. That doesn’t mean we shouldn’t keep working on it. Of course we will.

For type 2 diabetes, we face a real challenge. We already know a major way to decrease incidence of the disease, yet we can’t seem to influence the public to achieve that goal. We hope that we will have newer and more effective agents to control blood glucose levels so that even though people have the disease for longer periods, they will have fewer complications.

COPYRIGHT 2001 Saturday Evening Post Society

COPYRIGHT 2001 Gale Group

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