The statistics have been reported in all the major news magazines, on the nightly news and in newspapers from coast to coast.

Overall, adult men and women are about 8 pounds heavier, on average, than they were 15 years ago. According to the National Institutes of Health, over 100 million Americans – or about 60 percent of the adult population – are overweight.

As many as a third of Americans are considered “obese,” a term that in general is applied when a person is 20 percent or more above their ideal body weight.

Because being even 10 or 20 pounds overweight can be enough to trigger type 2 diabetes, the 33 percent rise in diabetes over the last decade is not particularly surprising to scientists, although it is alarming. What’s equally disturbing is that type 2 diabetes is striking younger people.

What is contributing to the growing obesity problem? Is it just our sedentary lifestyle, our addiction to fast food and our love affair with the television remote control? Or is there more than meets the eye? What can be done to reverse the trend?

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According to Joslin Diabetes Center’s new chief of the Section on Obesity, Eleftheria (Terry) Maratos-Flier, M.D., there is much for scientists to learn about the underlying role of genetics and environment in obesity and other factors to explain why we as a nation are gaining so much weight now.

“In the last five years there have been tremendous changes in how scientists view obesity. The long held view that obesity is caused simply by overeating and weak willpower has begun to change as we have learned about other factors that control weight,” says Dr. Maratos-Flier. “We now understand more about the role of the brain, in particular the hypothalamus, the part of the brain that seems to regulate in part how much we eat.”

Is it nature or nurture?

The role of genetics, and the role genes play in the body’s ability to produce and use certain hormones is being increasingly examined to determine what role heredity and hormonal imbalances have on eating and obesity.

Some of the hormones being studied are thought to keep body weight stable by controlling appetite. Others react to signals from the body that it is not fat enough, making people feel an urge to eat. Many scientists now believe that people’s eating is controlled by these types of molecules that send signals between the brain and the body. Obese people are likely to have an imbalance in the levels of these molecules or, at the very least, their body is less responsive to these molecules and therefore doesn’t get the message to stop eating.

Leptin, for example, is a hormone secreted from fat that seems to stimulate a section of the brain called the hypothalamus, thereby controlling appetite. In normal animal models scientists have observed that as more leptin is produced, appetite decreases. The role of leptin became evident by studying a strain of mice that are naturally extremely obese. These mice, called ob/ob mice, have a gene defect that makes them unable to produce leptin. In the absence of leptin, these animals eat, eat, eat. They become profoundly obese and develop diabetes. By giving these mice leptin, scientists have observed that the mice eat less and have a more normal weight.

“It appears that in the absence of leptin, these animals – and perhaps humans – never feel full when they eat, so they gain weight and become obese,” says Dr. Maratos-Flier.

Other studies suggest that animals that become obese when exposed to normal diets continue to eat perhaps because being overweight somehow decreases the animals’ ability to feel full. There may be a defect in the levels of leptin being produced, or there may be other defects in hormone production that cause this vicious cycle.

For example, Dr. Maratos-Flier’s group is studying the substance melanocyte stimulating hormone (MSH) and melanin concentrating hormone (MCH). In mammals, these two substances seem to predominantly affect appetite. In rats, for example, too much MCH seems to cause animals to overeat, and MSH seems to inhibit feeding. Dr. Maratos-Flier’s group discovered that MCH causes animals to overeat – and they also observed that MCH seems to be overactive in the ob/ob mice, which also lack the appetite suppressant leptin.

Just how exactly do these various substances interact to regulate appetite – and how do their production and actions become out-of-balance, leading to obesity and diabetes? This is a major focus of the Maratos-Flier lab. Because the process by which MCH, MSH and leptin exert their influences involves a complex set of chemical process that are not completely understood, there are lots of places in these processes where a malfunction could lead to obesity. For example, is there a problem with the receptors for MCH, leptin or MSH on cells, that leads the body to overproduce one hormone or another, leading to an inability for that animal to feel full and thereby causing it to overeat? And does what is learned in mouse and rat models translate into a logical description of what is happening in humans?

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“A single genetic mutation can lead to obesity in mice. A single mutation could lead to obesity in humans,” notes Dr. Maratos-Flier. Joslin President C. Ronald Kahn, M.D., and colleagues published a paper in the New England Journal of Medicine in 1998 showing that a defective gene, PPAR, produces a protein that is involved in one of the steps in the production of fat cells. When there is a mutation in this gene, which occurs in about 3 percent of the population, there is an increase in fat cell growth that contributes to obesity.

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“Genetics seems to determine the predisposition of mouse populations to obesity,” she says. “Similarly, approximately 5 percent of morbidly obese humans have a mutation in a brain molecule important for signaling them to stop eating. Even run-of-the-mill predisposition to obesity, we believe, is genetically determined in mice, and in humans.

“The simple decisions of what, when and how much to eat may not be completely under people’s conscious control,” she says.

If it’s all in the genes, why so much obesity now?

So if genes determine who will be fat or thin, and scientists have yet to determine what the magic pill is to affect the molecules that tell a person when to stop eating, should some people just resign themselves to a life of being overweight? Are efforts to fight the battle of the bulge simply an exercise in futility?

No, it’s not that simple either, says Dr. Maratos-Flier. What we see these days is that people of certain ethnic backgrounds who had very low rates of diabetes – Asians, Native Americans, and other groups – are now developing higher rates of diabetes as they adopt more “westernized” lifestyles that include more food and more sedentary lifestyles.

The gene pool hasn’t changed in these groups over the past 50 or 100 years – their environment and their lifestyle changed. Scientists hypothesize that some of these ethnic groups have what they’ve termed a “thrifty gene” in their biological makeup. This gene (or group of genes) enabled them during centuries of living as hunters or farmers to survive on relatively small amounts of food, thereby being able to survive periods of famine, for example. But now these individuals live in a society where high-calorie, high-fat food is readily available. They don’t need to expend nearly so many calories hunting or farming or doing all the various activities that were required to eek out an existence in the past. Instead, they are sitting at a desk or in front of the TV. And so they gain weight much more easily, and then develop diabetes.

In this circumstance, a genetic benefit – the “thrifty gene” – has become a genetic problem because of a change in lifestyle and environment. The potential solution, therefore, is to try to replicate some of the favorable aspects of their former environment – namely more exercise, and decreased food consumption.

What’s the connection between obesity and diabetes?

The role of obesity in diabetes is clear – but not understood. “Ninety percent of the people with type 2 diabetes are overweight,” says Dr. Maratos-Flier. “Certainly that is not a coincidence.”

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A particular type of fat – so-called visceral fat that is located in the stomach area and results in the proverbial pot belly – seems to increase the risk of developing diabetes. While scientists don’t understand why, it appears that when a person has a lot of fat in the abdomen, there are increased levels of free fatty acids, and these free fatty acids alter the way insulin works in the body, producing a state of insulin resistance that leads to type 2 diabetes.

How to shed those unwanted pounds?

The choices in weight loss diets abound. For some trying to lose weight, meals come in the form of a nutrient packed drink, for others it’s following a daily regimen of calorie-counting, or carbohydrate-counting, or fat-gram counting.

One thing virtually everyone agrees upon: once the excess pounds are there, they are hard to lose. For that reason, prevention – not gaining excess weight in the first place – is the most prudent measure. According to a recent article in the New York Times, more than 90 percent of those who diet gain back each pound they lose and no particular diet or behavior modification program has been able to turn around these odds.

“One of the frustrating things about treating patients is that while weight is a major issue from the point of view of obesity, as physicians we don’t have any quick-fix diets to recommend,” says Dr. Maratos-Flier

“Portion control is the real issue if you want to lose weight. Yet we Americans have a cultural thing about portion size,” she says. “In the United States, portions tend to be large. All-you-can-eat buffets are popular. People feel they have to eat a lot to get their money’s worth. For an extra 5 cents, they want to upgrade to the larger size.

“A trip to a steakhouse can mean downing a 16-ounce steak that represents over 1,300 calories. And that doesn’t count the potato with the sour cream, or the vegetables that might come with it. It’s a culture where it’s acceptable to eat a 16-ounce steak or piece of prime rib. A culture in which we think if we’re getting anything less than a 12-ounce steak that we’re getting ripped off.”

While many medical professionals at Joslin and elsewhere may point to the burgeoning reliance on fast food as a culprit in the bloating of America, Dr. Maratos-Flier is a little less critical. “If you’re educated about calorie content, there’s nothing wrong with fast food. McDonalds is not the culprit.” She cites a fine restaurant in Cambridge where you can spend $35 to eat unlimited selections from a sumptuous buffet. “Instead of gorging at the restaurant, you could choose a McDonalds hamburger (280 calories) and small fries (210 calories) and come out ahead calorie-wise,” she says.

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People also should assess the nutritional value of what they eat, not just the calorie content. For example, she points out that Doritos and pretzels have the same amount of calories and lack nutrients. “If you eat broccoli instead of Doritos – that’s a good thing. But if you eat a large quantity of pretzels, the calories could equal those of several handfuls of Doritos,” she says.

Clearly, if a person is overweight and has diabetes, what to eat and when becomes much more complex issues. Coordinating how much is eaten with when oral medications or insulin are acting is vitally important, and should be discussed in detail with your health care team, including your doctor and your dietitian. Also, many people with diabetes or who are obese may have high blood pressure or high fat and cholesterol levels – and therefore need to limit the amount of high fat foods in their diets.

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Dr. Maratos-Flier looks at the debate about higher fat vs. higher carbohydrate diets for people with diabetes trying to lose weight and feels that higher fat diets may have their place. Unlike many who advocate low-fat diets, Dr. Maratos-Flier thinks people who do not have special risk factors such as high fats in the bloodstream do not necessarily have to cut back stringently on high fat foods like steak or cheese. She recognizes that this puts her in the minority among those who treat diabetes patients at Joslin and nationwide. “But in my opinion, there is no scientific evidence to suggest that people on low-fat diets are more successful at losing weight than those who include more fat in their diet,” she says.

What is the role of exercise?

Unlike diet, where the debate over what works best to help people lose weight remains, there is no question about the role of exercise. “People should just do it!” she says. She recommends people perform 20-30 minutes of aerobic exercise five times per week, after receiving clearance from their health care provider. “You want to get a rise in your pulse, depending on your age and level of fitness. You can increase your level of exercise in everyday activities – by parking your car at the edge of the mall parking lot and walking, rather than parking as close as you can get. By taking the stairs instead of the elevator. Walk to the restaurant furthest away for lunch instead of going to the one that’s closest. Physical activity is helpful for conditioning, even without weight loss. And if you have diabetes, it will help you use insulin better to keep your blood sugars better managed,” she says.

Psychological reasons to overeat?

“Many people eat to self-medicate,” says Dr. Maratos-Flier. “Like the coffee drinker who needs that jolt of caffeine each morning to get them going-people, especially those who binge uncontrollably on large amounts of food at one time are medicating themselves. They are using food to treat their depression, loneliness, and anger,” Dr. Maratos-Flier says. Even those who don’t binge may discover that eating increases under times of stress or sadness. Charting what triggers you to eat or overeat can lead to increased awareness – which can be the first step toward making a change in this behavior.

Is surgery ever an answer?

Gastric bypass surgery is a procedure in which, in one of the most common methods used, the stomach is made smaller so that food intake is restricted, and part of the small intestine are bypassed to reduce absorption of calories and nutrients. While many medical experts consider gastric bypass surgery radical, Dr. Maratos-Flier does not consider this procedure unreasonable to consider for some patients, such as those who have a Body Mass Index (a way of calculating the percentage of one’s body that is fat) of over 40. Weight loss at this level of obesity can have a dramatic impact on morbidity and mortality. She occasionally refers patients to Beth Israel Deaconess Medical Center, where the procedure is done.

Before surgery, however, it’s important for the patient to follow a medically approved diet plan and for the patient to be willing to take steps to keep the weight off after the surgery. One patient she saw lost 80 pounds after having the surgery and found relief from joint and body pains too. He was able to reduce the number of medications he took as well. However, as with any surgery, the procedure has risks and the patient still needs to follow a healthy diet and exercise program to maintain the weight loss.

Will there be a magic pill for desperate people?

While existing obesity drugs generally do not work or have side effects potentially more deadly than the condition itself, drug companies are working feverishly to develop safe drugs to help those stubborn pounds come off.

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“It’s reasonable that there’s a chance one day several weight loss pills that are safe and effective will be developed,” Dr. Maratos-Flier says. But most likely it will involve several pills being developed that target different factors rather than one pill that does it all. “It’s likely people who are obese would take two or three pills targeting different malfunctions in how their body recognizes when to eat and when to stop eating.”

“While it seems like it might be a long way off, the research suggests that it can definitely happen.”

Source: Joslin Diabetes Center