[MUSIC] Almost everyone has heard that physical activity is healthy, yet most of us skip our daily exercise more often than not. What most of maybe don't understand, however, is the reason why exercise is healthy and beneficial in relation to both prevention and treatment of diabetes. So, let's take a closer look at how this works. Research shows that exercise stimulates the molecular processes that form the basis of the development and treatment of type 2 diabetes, by increasing the ability of skeletal muscles to respond to insulin, and thereby, enhancing the muscle's ability to convert glucose to energy. The muscle cells undergo a transformation, already the first time you start exercising. And furthermore, this can lead to changes in nothing less than our DNA. Professor Juleen Zierath, a recognized expert within this field, will introduce us to a more detailed description of what actually happens in the body when we exercise, and why these changes help us to prevent and treat diabetes. Welcome to the discussion Juleen. So I'm interested to know what exactly happens to the body when we do exercise. >> Well when we exercise, there is multiple changes that occur in many organs in the body, but my interest has been mainly focused on muscle tissue. And so the muscle tissue adapts based on the kind of exercise, the duration of the exercise, and the intensity of the exercise. For example, if you do endurance exercise, maybe running ten kilometers, you have a recruitment of muscle fibers. But maybe not all the muscle fibers. Because you don't need to do high intensity work, it's a low intensity endurance exercise. And in that exercise, you're utilizing, primarily, carbohydrates first, but then lipids as a fuel base. If you do strength training, weightlifting, or explosive exercise, you're recruiting much of the muscle mass, and you're utilizing primarily sugar or glucose as a fuel source. So different modes of exercise, weight training or endurance training, the duration, if it's minutes or hours, and the type of exercise, affects the muscles and how the muscle metabolizes fuels, and how the muscles cells are recruited to do the work. >> So we're talking about the muscle, what exactly happens in the muscle? >> So one of the primary things the muscle needs to do work is sugar, it needs glucose, it needs to have that to make ATP. So one of the things that happens is that there's proteins on the cell surface of the muscle, and they move sugar, glucose, into the muscle cell for metabolism, for fuel. The muscle also breaks down its own source of fuel, glycogen. So one of the first things that happens, the muscle needs to get fuel, bring in either sugar in from the external, the circulation, or utilizing the fuel that's stored in the muscle cell itself. >> For many years, it's been a mystery what exactly happens in the interaction between insulin, glucose, and muscle cells. Your research has uncovered the mystery. Tell me a little bit about that. >> All right, so I talked a little bit about the muscle, and I talked about the muscle needs sugar, it needs glucose. There's two things to know. If you're a diabetic person, you have resistance to the hormone insulin, and you're not able to take sugar into the muscle cell, that's the trigger. Insulin leads to a cascade of events that recruits proteins into the cell and brings in sugar. Simple process, bringing sugar from the outside into the cell. In diabetes that is disturbed. When you exercise, you're able to recruit sugar from the blood into the muscle cell for fuel, and even if you're a diabetic, that process works. That process is preserved. So when people are diabetic, they're insulin resistant. They can't get sugar into the muscle cell. But if they exercise, the exercise leads to a process that brings sugar, the necessarily fuel source, into the muscle cell for metabolism. So those are the two things that we've learned. One, in diabetes, the process is disturbed. Two, with exercise, you can circumvent these disturbances in diabetes, and you can get a normal glucose uptake. So exercise is like a medicine, it can go around the defects that you have with diabetes. >> So, leads me to my next question, which is, your research shows that we can change our DNA through exercise. So, please explain how that's possible. >> Well, you can't actually change your DNA code, that's something that you inherit from your parents. But you can change the way in which other molecules perceive the DNA you have. And one of the ways to do that is with exercise. A really early trigger for remodeling a cell like muscle in response to exercise, is through a process called epigenetics or epigenomics. And this is a process where there are chemical marks that are either placed on a DNA, or lost form the DNA. And these chemical marks change the way other molecules perceive the DNA. In other words, these chemical marks either prevent or allow molecules called transcription factors to bind to the DNA, and initiate a program that can reprogram the muscle cells. And they can make them produce molecules that can improve metabolism, or they can help the muscle cell grow. So that's one of the earliest changes, exercise can reprogram or remodel the muscle, partly through an epigenomic change, by altering the chemical marks on the DNA. >> As we've heard Juleen Zierath explain, physical activity has the capacity to transform cells, to open pathways, and even to change our DNA. Will exercise then maybe also affect the genes and health of someone not even born yet, our unborn children? This may sound impossible, but a scientific study published in 2015, in the journal of Cell Metabolism, revealed that exercise changes certain genes. Which again regulates sperm cells appetite, making sure that these genes will be pass on to the next generation. These findings were a huge surprise to the researchers, because they suggest that the way we pass on good, as well as bad genes, is much more complicated than we previously believed it to be. Simply put, our level of exercise does not only affect our own body, but also may affect the body of our future children. In much the same way that we have been affected by how much or how little our parents and grandparents exercised. So how is this possible, you might ask. Let's talk to medical doctor Ida Donkin who is part of a researching team looking at lifestyle and sperm cells. So welcome to the discussion, Ida. >> Thank you. >> What exactly is the research you found on this? >> So what we found in our studies is that sperm cells seems to remember your bad habits. So if you're obese as a man or if you have a very low level of physical exercise, physical activity, it seems that your sperm cells are affected by this. And what our study suggests is that this bad memory will be transferred to change the development of your children and change their risk of getting diseases like obesity and diabetes later on. >> So the research found that potentially my lifestyle could affect my future children. >> Yeah, yeah, we could see that when we looked inside the sperm cells. We investigate it in the paper we've published last December in Cell Metabolism. That when we looked at sperm cells from obese males, their core material changed a bit. And when I talk core material I talk about something called epigenetic factors, because we know that inside our sperm cells and our egg cells we of course deliver genes to the next generation. Genes that we have inherited from our parents. But we also deliver something else to the next generation and this is the memory of our lifestyle. These epigenetic factors are molecules placed around our genes being able to turn either the gene on or off, to change the expression of genes and development of proteins inside our body. >> So is epigenetics one of the reasons why obesity and diabetes are on the increase? >> It's very likely so, it's rather new that we can see that epigenetic factors, meaning traces of our lifestyle, is actually being transmitted to the next generation. But we think this might help explain why diabetes and obesity is on the rise as we see it in the Western world, because genetics cannot solidly explain why the inheritance of those diseases are so great. And maybe epigenetics is the missing link here. >> So do you have any good advice for myself, maybe as a future dad or other future dads? >> Yeah, I would suggest that you would try to stay healthy in your eating habits and do a bit more exercise in your normal day. And this is advices that we have been giving to mothers-to-be for ages. Because we know that it's important for the future children that they grow up in an environment that's healthy. And it seems now that those health advices might be good to give them out to future dads-to-be as well. Because their sperm cells might be affected by their bad habits. And that this might affect the development of their children. >> If my sperm cells affect my future children, and my father's sperm cells affected me. How many generations does it go back or forward? >> We're not so sure about this yet, but we can see them in some rodent studies we do when we look at rats, for example. And this is a study we published in this January as well. We see that if we feed a rat a very fat diet, a male rat. That the following two generations will actually be affected by this. Developing disturbances in the body that reflects diabetes and obesity. So at least we think that it goes two generations. But we're not sure how much more it will be transmitted. >> So if my lifestyle, exercise affects my sperm cells and I want to become a dad. How long do I need to get a good lifestyle before I have my child? >> Well, our results are not quite clear here. Because it seems that some kinds of the epigenetic patterns around your genes are very dynamically regulated, meaning that just exercising six weeks is enough to change the epigenetic patterns, whereas around other genes, it seems that they have a more long lasting memory, showing that if you exercised several months ago. This still has a positive effect in your sperm cells. So it may be that you will have to have a healthy lifestyle several years before you want to have your children. But it may also be that for some genes it's actually important what kind of diet you had just the day before. >> It seems like our future generation's health is highly dependent on the lifestyle choices we make today. Most studies, including the ones we mentioned earlier, talk about the Western world and how we must combat physical inactivity to prevent and manage diabetes. But very little is known about the causality between exercise, physical inactivity, and diabetes in low and middle income countries. And numbers show that the percentage of populations in urban areas in these regions suffering diabetes has increased from 1.4% in the 1980s to currently 7%. We also know that this, at least partly, is due to the population's embrace of a Western lifestyle. Characterized by, for example, an increased intake of fat and sugar combined with a less physically active lifestyle and lower quality of sleep. But what about the millions and millions of people living outside the urban areas and the low end middle income countries? Are people in the rural areas not at risk of getting diabetes related to low physical exercise? Let's listen to what associate professor, Dirk Lund Christensen, has to contribute on this question. Dirk Christensen has for decades studied lifestyle developments in rural areas in East Africa and other low and middle income countries. What can we learn from your research regarding the importance of physical activity and diabetes? >> Well, first of all we have been studying rural and urban populations. So we can distinguish between people living in a more traditional way and people living in a more, let’s say, modern way. And there is a clear distinction when we measure physical activity. So those living in the rural areas are still very physically active. And those living in the urban areas are much less physically active. And there is a clear association between physical activity and the risk of diabetes. So those who are not very active have a much higher proportion of diabetes than those who are less active. >> Can you give us an example of how physical activity relates to diabetes? >> We've done a study in the south of India where in young men who were born low birth weight and compare them to a group born with normal birth weight. But these young men who were born with low birth weight were born within term, so between week 37 and week 41. And they were exposed to an intervention of bicycling to and from work, 45 minutes a day for 6 weeks. And we wanted to explore whether they would get some of the positive effects of physical exercise. That we have seen is not the case if you are born preterm and low birth weight. So here you have a special group, you could say which is very common actually in low middle income countries. That is low birth weight, but born within term. So, after this study they were measured, we had many different measurements, blood sugar, one of them, before the study, the six weeks intervention and after the six weeks, but also body composition, and we could see that they did actually benefit from this interaction. Sorry, this exercise intervention, when it came to blood sugar, and then when it came to the body composition. So they had more lean body mass and they had less fat mass in their body, which is positive. >> Do you have another example of how physical activity relates to diabetes? >> We can the Maasai people in East Africa, so in this case in Kenya. We measure this about 370 of these people. And the activity is so high that it would, if you compare that activity to a European population, in an urban European population, it would be equal either one hour of running or two hours of walking each day throughout the year, that's the difference. So, we would have to do that amount of exercise in order to be just as active as Maasai people. And they have very low prevalence of diabetes. It's important to distinguish between the lifestyles of those societies. So here in the Western World, we tend to have a work life that is inactive and a leisure time life that may be very active for some people and not for others. So we have some who are extremely active and that's mostly men. Women are not as active in their leisure time, so there is a distinction there between men and women. But in the low and middle income countries, people don't have this distinction between work life and leisure time life. So the activity that we see there is mostly from transportation to and from work, transportation, sorry, exercise if you will during work, so physical exercise. Of course, when they moved to the urban area and they get white collar job, an office job, they adapt the lifestyle from the Western world. And if they then do not also adapt the leisure time activity that we have here, then they will become inactive and more prone to obesity and diabetes. >> So why is it important that we have research from low and middle income countries? How can that help the bigger picture? >> Well, they are often, we see extremes in low and middle income countries that we don't see in the industrialized world. So I think these extremes that will help us to understand the association or even the mechanisms much better. So that we can say that maybe there's a specific level of activity we need in order to stay fit or to be disease free, if you will. Or it may be that the intensity of the work you are doing has to be at this or this level. Which leads me to the next, let's say, sub theme of this physical activity, namely the intensity. And I think what our study has shown, our studies have shown from Africa, is the fact that these people are not very, they're not active at a very high intensity. Which is good news for all people because it means you can, given that you have high physical activity. As long as it is high, it doesn't have to be, as long as the level of physical activity is high, intensity doesn't have to be high. So you don't have to run marathons or be an elite athlete in order to stay fit. >> Are there any rules or guidelines that we can follow? >> The World Health Organization put forward guidelines about five years ago, official guidelines, saying that activity five times a week at half an hour a day, at moderate intensity is the minimum in order to stay fit. So that would be to prevent for example, diabetes. Or you could choose to be active at half that amount of time but at high physical intensity. So you can go in each direction and the higher the intensity the less time you need to use, so that's how it goes. But that's for adults and for children is actually an hour a day and not half an hour. But if we go back to physical activity, here we did show that those who are more physically active, namely those in the rural areas, have less diabetes than those living in the urban areas, who are less physically active. So we can say from that study that the association between diabetes and physical activity is quite clear. >> So take me as an example, I exercise three times a week, I don't think I'm overweight, so does that mean I'm home safe from the risks of diabetes. >> May be, may be not, you can't say that for sure, it depends on the intensity, it depends on your risk profile as an individual. When I'm talking about exercise and diabetes, I'm speaking from a population point of view. And there will always be individuals who don't fit into this box of exercise and diabetes. But what is important here to emphasize is that being normal weight is in itself not enough if you want to stay disease free, and let's talk about diabetes here. So, if you're normal weight and you don't exercise at all, you may also have what is called a thin fat body profile. So you have a lot of fat mass, and relatively little lean body mass for a given weight, and you may be at risk of diabetes. Vice-versa, you may be over-weight, say you have BMI of 26 which is one above the cut point for being over-weight and you are very active, and that may be enough for you to stay disease free and not have high blood glucose, for example. So there are this different combinations and exercise or not exercise is very important no matter where on the scale you are when it comes to your weight. >> That physical activity plays a very important role in relation to diabetes seems clear. And even though a genetic factor also plays a role, we are even, by exercise, able to change our unique set of DNA. Or in other words, the genetic instructions that are determining development, functioning and reproduction. This means as Ida Duncan explained, that our physical level of activity will play a role for future generations, too. [MUSIC]
