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Dr. Mooradian: The issue of being fit and its correlation with mortality or outcome measures: the data you showed, specifically the data in type-2 diabetes and any other data in the literature, are mostly correlations and they are very hard to pin down to fitness. A lot of the time people who tend to be fit are also healthier individuals, so overall other co-morbidities will be less so. It is very hard to sort out fitness as an independent predictor of outcome. Another issue is that, as far as I know, there are absolutely no data to show that, as you recommend, increasing food intake and exercise actually improves longevity or health, other than the non-tangible benefits of exercise that we are all aware of, and there are many benefits of exercise. In contrast, a lot of data show that if you restrict food you improve life expectancy invariably in many species. So if you want to make a recommendation based on outcome, it seems to me that it is better to restrict food rather than liberalize it, and then do a lot of exercise.
Dr. Hill: Let me deal with both those issues because these are really good questions. I am glad you asked about the fit and fat issue. Even though people call it a controversy, it isn't. I believe the data suggest that whatever your fatness level it is better to be fitter, and whatever your fitness level it is better to be leaner. We can produce significant weight loss in patients with a BMI of >40, but most will still be overweight or obese. Our treatment for these individuals should be aimed both at producing weight loss and increasing physical fitness. As we are more successful at doing this, we will create more fit and fat people. The research on caloric restriction and longevity is very interesting. There were some data presented at the obesity meetings in Vancouver suggesting that increased exercise may also positively impact longevity. The question is whether it is calorie restriction or avoiding positive energy balance that increases longevity.
Dr. Metzger: Do you see any allowance for an inherent influence on the level of physical activity? The reason I bring this up is that there have been some reports that already from intrauterine time onward babies predisposed to have more body fat and individuals predisposed to be heavy already have a reduced level of physical activity.
Dr. Hill: This is an interesting concept to consider. We are learning that the intrauterine environment can have a major impact on metabolism and weight later in life. I don't think we have any data about this, but it is certainly possible that the intrauterine environment could affect later physical activity.
Dr. Bantle: We commonly think of exercise as a means of expending energy and that is the mechanism whereby it influences weight. But I wonder about another possibility. Distance runners are uniformly lean and I ask myself why. Is it because they can't eat enough to keep up with their exercise? In fact, what they eat is absolutely astounding in terms of amounts and calories. So my question is, could there be another mechanism involved here? Is it possible that the hypothalamus responds to the level of habitual physical activity and adjusts body configuration to conform to the need? In effect, the hypothalamus might say, 'We have to run 50 km/week and we need to stay lean to do that'.
Dr. Hill: We know the brain is very important in body weight regulation but it is not totally clear what is being regulated. The brain could be regulating an amount of energy intake, an amount of physical activity (or energy expenditure) or an amount of body weight or body fat. Distance runners are a unique group and it is possible that they are regulating around a high level of physical activity. Alternatively they may be regulating a high level of energy intake and the high levels of physical activity are necessary to keep them lean. I think that people can modify their physical activity level to some extent and that the level of physical activity affects the sensitivity of many metabolic processes in the body. I see the sedentary state as the abnormal state so rather than have a note from your doctor to exercise, you should have a note from your doctor to be sedentary. There is some evidence from the Pima Indians that leptin regulation may be different in the Mexican Pimas who are much more physically active than the Pimas in Arizona. So I think we may find that the level of physical activity plays a role in the precision of regulation of some metabolic processes. The brain and specifically the hypothalamus are almost certainly involved.
Dr. Chiasson: I was wondering about the obese population that you followed in the registry. You said that in those who maintain moderate exercise, their body weight is gradually reduced through exercise. Is that a failure to moderate exercise or a failure to follow diet over time?
Dr. Hill: The short answer is we don't know. What we know is that the people who are successful at weight loss maintenance report high levels of physical activity and people whose exercise decreases over time gain weight. There are several studies that suggest that people who are only moderately active are unable to maintain their weight loss. It seems to take a lot of exercise to maintain large weight losses. I think the amount of exercise you have to do is related to the amount of weight you lose. The more weight you are keeping off, the more you have to exercise.
Dr. Chow: It is possible to induce someone to engage in some exercise; perhaps you can effect a change of mind so they will be more self-disciplined which means that they probably will also be more compliant in diet and follow the guidelines from the medical profession. Do you agree, and do you have any evidence for this?
Dr. Hill: That is a good question and that is one of the alternative hypotheses for why exercise is always such a great marker of success in weight loss maintenance. It could simply be a marker of compliance, so if a person is exercising regularly they are also more likely to be eating healthily. One reason I think exercise itself is important is that when we estimate how much metabolic rate should have changed with weight loss for people in the National Weight Loss Registry, the amount of exercise they are doing is very close to this value. Thus, I think the advantage of high levels of exercise is that it allows these people to maintain a lower weight with having to engage in constant food restriction.
Dr. Slama: For the sake of the discussion I would like to recall the words of Winston Churchill. When he was asked the recipe for his long life he said: no sport, no sport at all, Scotch and cigar every day. I would like to challenge the idea put forward by Elliott Joslin who said that you cannot treat diabetes without exercise, insulin and diet, and more precisely that you cannot control diabetes without exercise. We did a study in our department showing that there is a population of diabetic people who is very well controlled with a very low level of exercise. We also have type-1 and type-2 diabetic people who are very badly controlled with a very high level of exercise. In any direction you can find something, but you may also observe a large population of patients with a very low level of exercise and perfect blood glucose control. But of course exercise has a much more important effect on life: cardiovascular disease prevention.
Dr. Hill: You make a very good point. In the National Weight Control Registry for example there are about 9% of people who are maintaining weight loss without exercise. So I do think there is going to be a population for whom exercise may not be effective and diet is critically important. I think there is probably a population for whom exercise is tremendously important and exercise alone may be sufficient to maintain a healthy weight. Most people are going to be in the middle where exercise is going to help but diet changes are also needed. The more I look at this issue, the more I believe that exercise is more effective the earlier in the cascade of chronic disease you are. I think it is the most effective in preventing obesity and diabetes in lean people. I think the more you go down the path toward diabetes and cardiovascular disease, the more exercise you have to do to positively impact health.
Ms. June Chan: You mentioned that in the National Weight Control Registry most people use walking and some use resistance training. Do you have any data showing that resistance training plus aerobic exercises is going to be better than aerobics alone in terms of weight maintenance or obesity prevention?
Dr. Hill: We looked at the proportion of people in the registry who reported engaging in resistance training or weight lifting versus the proportion in a general survey of the American population. A higher proportion of women in the National Weight Control Registry (15-20%) reported engaging in resistance training as compared to women in the general public (5-6%). We do not know if this is a factor in their success or not. There are some data in the literature showing that resistance training has similar effects to aerobic activity in obesity treatment. I don't think resistance training can totally take the place of aerobic activity, but it can be a positive companion to aerobic activity.
Dr. T. Wilkin: I was interested in Dr. Bantle's comments on the hypothalamus and the possibility that it censures the physical activity that is accomplished. We study physical activity in children, and about 18 months ago reported in the British Medical Journal  a study in 3 different schools with very different opportunities for physical activity. In one of the schools it was 9h and in another school under 2h, so it was a very big range. As you might expect the activity of the children in the school that gave the most opportunity did much more during the day time. We used accelerometers to measure this, so these would be reasonably objective measurements we were making. However, when these children got home in the evening they just flopped. The children who got under 2 h perked up in the evening. If you added the out-of-school to the in-school activities, you got the same over the whole of the range. This lead us to do a number of other studies, all of which put together suggest very strongly that there is an activity stat, at least in children, which regulates the amount of activity they do. I suspect that as children become teenagers and beyond there may be social cues that may override this, but it is probably most strong in children.
Dr. Hill: I think it is a possibility. I know there are some data in elderly people showing that when they were given a supervised exercise program that they were more sedentary in the rest of the day. But I am very skeptical that the amount of physical activity is fixed. Again, people in the National Weight Loss Registry were able to maintain large, permanent increases in physical activity.
Dr. Barclay: You mentioned the importance of breakfast, and we often hear that it is better to get your calories more in the morning than in the evening. What is the evidence for that in terms of weight maintenance and weight loss?
Dr. Hill: There is a fair amount of evidence that eating breakfast has a positive effect on body weight. First of all there are several epidemiology studies showing that people who eat breakfast are leaner than those who do not. There are studies reporting that people who eat breakfast end up eating fewer calories during the day than those who do not. Finally there are studies showing that satiety is highest for food eaten early during the day compared to food eaten later in the day. So we have a lot of circumstantial evidence suggesting the importance of breakfast for weight management.
Dr. Golay: You propose 60min of exercise for obese patients but in fact they should have even less than that because they are obese. The energy expenditure in obese patients is much higher, so I would propose even less than 15min for obese compared to lean patients.
Dr. Hill: I don't think 15 min is enough. You are correct that obese people have a higher cost of exercise, but I still think it takes about an hour a day of exercise to maintain a large weight loss. I think this may be because subjects are making up for some sort of metabolic price of being obese.
Dr. Metzger: I want to come back to the question about the calorie distribution through the day. There are animal models from 45-50 years ago showing that calories remained constant. If a large proportion of calories is administered to experimental animals in the latter half of the day, equivalent to our dinner time, body composition is significantly affected resulting in more hepatic lipid synthesis, increased body fat at the same isocaloric intake. I think there have been some human studies that would be consistent with that, but obviously they can't be as interventional as the animal studies.
Dr. Hill: I think we see that pattern. I know you all see it in your obese subjects who skip breakfast, eat a light lunch and start eating at 3 or 4 in the afternoon and eat all through the night. This may be the worst meal pattern. I think that by eating breakfast you break up that pattern and this may be beneficial.
Dr. Ho: I have a question regarding the relationship between the exercise and the timing of meals.
Dr. Hill: I believe that the most important decision is whether to exercise or not regardless of when you exercise. The literature is mixed regarding the interaction of eating and exercise. My reading of the literature is that if there is an interaction, it is small. The far bigger effect is whether you do any exercise or not.
Dr. Halimi: Regarding type-2 diabetic patients, one of the major objectives is the control of glycemia, not only for reducing the high cardiovascular risk but mainly for preventing microangiopathy. In your opinion what is the best duration for reducing glycemia if we consider that the body doesn't burn the same fuel according to the duration of a physical exercise and what training could change?
Dr. Hill: So you asking how the interaction of exercise and meals affects glycemia during the day? I think that is an interesting question and that is where perhaps exercise and meals might play a role. If it is glycemia that is the issue, then the timing of exercise in type-2 diabetes could be important.
Dr. Halimi: Not only because of the time of the meal. After 30 or 45min the fuel utilized changes, and there is some evidence in favor of a longer duration of physical exercise in type-2 diabetics when compared to obese patients.
Dr. Hill: There is a tradeoff between the duration and intensity of exercise. The effects depend on intensity and duration. The more intense you exercise the more carbohydrate versus fat is oxidized. Moderate intensity longer duration exercise burns proportionally more fat but less calories. For weight management in non-diabetics, the total amount of energy expended in physical activity is probably more important than the timing and intensity. For diabetics, the timing and intensity may be more important and could affect glycemia during the day.
Ms. Franz: A concern I have with the Weight Loss Registry is that it may lead individuals to have unrealistic weight loss goals. While there are participants in weight loss programs who will lose larger amounts of weight and those who will lose none, the majority will likely lose 4.5-7.5 kg at 12 months and, with continued support, maintain a weight loss of 3-4 kg [2, 3]. They will not be as successful at weight loss as the individuals in the Weight Loss Registry but will still experience health benefits as evidenced by participants in the Diabetes Prevention Program. Women participating in a weight loss program expected to lose 34% of their body weight, and despite a weight loss of 16%, they reported being unsatisfied with their weight loss . Baseline expectations are also reported to be an independent predictor of attrition in obese patients entering a weight loss program; the higher the expectations, the higher the attrition at 12 months . Although we can certainly learn from the participants in the Weight Loss Registry, it is important that persons attempting weight loss have realistic weight loss goals.
Dr. Hill: I agree totally. The whole point of developing the registry was not to look at the prevalence of successful weight loss maintenance but simply to look for similar behavior in those who are most successful. People in the registry have achieved a level of success that most people do not achieve. However, I think the registry helps us identify the kinds of behaviors that could help more people be successful.
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Bantle JP, Slama G (eds): Nutritional Management of Diabetes Mellitus and Dysmetabolic Syndrome. Nestlé Nutr Workshop Ser Clin Perform Program, vol 11, pp 197-206, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2006.
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For centuries, ever since the legendary Ponce de Leon went searching for the elusive Fountain of Youth, people have been looking for ways to slow down the aging process. Medical science has made great strides in keeping people alive longer by preventing and curing disease, and helping people to live healthier lives. Average life expectancy keeps increasing, and most of us can look forward to the chance to live much longer lives than our ancestors.