There has been some reluctance amongst diabetologists to acknowledge that tuberculosis was really a problem they should address. And vice versa. Therefore there was made a systematically review by the Harvard people: Murray and Jeon. And they simply made a meta-analysis of all published literature. And what did they conclude from this review? Diabetes was associated with an increased risk for tuberculosis, no matter which study design or no matter which population. But of course, how serious this outcome is depends on where you are in the world. If there's not much diabetes in the place, well, it won't matter a lot if there's not much tuberculosis in a place, it wouldn't matter much about comorbidity, but if you have both, which is the case in India, and China, and Indonesia, Bangladesh and Pakistan and Brazil, you will really have a problem. So, let's look at the map again. Here we have the present day situation on diabetes and tuberculosis coexisting. And you will see that there are large areas of Asia, South East Asia and parts of Africa where we have a very high incidence of tuberculosis. 200 to 300 per hundred thousand population and at the same time the prevalence of diabetes between 5% and 10%. This is where the meeting of the two is going to happen. And the problem is that we are not geared to do anything yet, because either you are an infectious disease specialist, pulmonologist, or diabetologist, endocrinologist, and you wouldn't think of anything but your own speciality. So a key question when an individual or population is undergoing a fast transition in living condition or lifestyle if you like. Well, could there be any other reasons to look a little beyond your scientific borders? One example would be to look into what happens already in mother's womb. If you have a situation where the mother is hard working, suffering from current diseases like malaria. Or has got chronic anaemia and so on and the child is in the womb to avoid to be aborted. This child will have to modify to survive. And of course to avoid being aborted or born too prematurely, it will modify the way its metabolism is running. The child is simply born insulin-resistant. That fits very well if it comes out into adult life doing the same as the mother. Hard working, exposed to malaria and other diseases, iron anemia, et cetera et cetera. It's perfect to have a slow running metabolism. But what happens if you get an education? You're urbanized, you get a white collar job sitting behind a computer, you become a school teacher, whatever. Is it then necessarily a good idea to have a low metabolism, and being born insulin resistant? We know that it's not good to be born from a fat mother, you get an obese child. But now there are some indications that being born small, and growing up in an urban environment could be deleterious. So, urbanization, transition in lifestyle, et cetera, could start very early in life and that's why I don't like the word "lifestyle" for diseases like diabetes. Low birth weight, is it prevalent in the developing world or low income societies? Very much so. It is defined as 2,500 gram or less. We have an epidemic now of diabetes in the world. Everyone is agreeing on this. But if we look into this table here we will see that obesity is only related to diabetes in the western world. If you go to Africa and Southeast Asia, less than 50% of all diabetics, type 2 diabetics are fat. So the good advice, you should exercise more, you should lose weight and so on. You should not have a body mass index beyond 25. They simply don't work in this setting. How come that people are having diabetes and hypertension without having a overweight? That's a key question. And we still don't have the answers. There has been numerous studies trying to explain: Oh it's because of the survival of the fittest over the years. They have been through starvation for the last 1,000 years and therefore they were selected, those were the genes that could resist hunger and so on. There has been a lot of studies in North-eastern China, trying to find these genes, but they were not found. You may explain less that 10% of all this inherited diabetes from the genes. It's not it. So what is it then? Why is it so prevalent now? Why are the leading nations for diabetes India and China, and Indonesia? Could it be something next to the genes? If it's not the genes, it must be the environment. So, well, there is actually something next to the genes. And, if you translate this from the genes that is also a Greek word and you say what is the next word here, by or upon the genes its epigenes. Is there anything named epigenes? Yes, recent research has shown that it is very, very important what is going on in your early life. If you are exposed to something adverse it will modify your genes. You'll not mutate something but your genes will simply be silenced and what we still don't know is whether this is permanent or not. It's a very simple procedure. It's simply, the methylation of the genes, as you can see from the next slide here. You all know that we have our DNA and in the DNA we have the various DNA bases, but if someone is inserting a simple molecule, CH3, on that same group nearby a gene, for instance, the insulin gene, then this gene will be silenced. So it's like a car. You still have a motor in the car, but there's something stepping on your brake, on your brake, and therefore, the car is not moving. So if you look are there any mutations in the genes, the answer is no! They are perfectly normal, but they're not working. So this methylation of regulatory genes may be the reason why we have got so much obesity, non-related, not related obesity to diabetes. You are simply programmed in early life. If this holds true you could start asking as we did with Darwin: Is it the survival of the fittest or is it the survival of the sickest? Those who have got a mutation in early life and we don't know. If you're programed to survive hunger and disease and you end up in an environment where this is no longer the case, then you are probably not programmed as you should be. Can we change that in one generation? That's the question. So low birth rate, that's the prevalent problem, but urbanization is going to change this. So those who were born low birth weight now moving into the cities, having a white collar job, are they going to survive in that new environment? Why is it that we're having all these non-communicable diseases in areas where people are not obese, maybe the answer is that they have been exposed, their lives have been determined very early on. That's why we'll have to do much more research about the interaction about early events in life including an errant pregnancy - and diabetes. Are these two links? First time you tell a politician or policy maker about this, he will think you are crazy. But if you try to say: this is not something new, we should change completely, we should do more of what we are already doing. Protect the mother, the unborn child on one side, against being too fat, on the other side, against too under-nourished and diseased. Then, people will not give up, and say, well researchers, they always give you advice on something new and forget about the old. You should do more of the old, but you should not forget about the new diseases as well. But how do we explain that in one generation you can go from over to under nutrition, and vice versa. Let's take the little, small undernourished mother. She gets a baby that's undernourished. This baby is born programmed to be insulin resistant to survive. It is getting urbanized. It gets relatively over-nutritioned, westernized food and so on. What's the result? Type 2 diabetes. On the other hand we have a fat mother. The child is already being too fat before it's born. It's getting early Type 2 diabetes as well. This time because it's too fat. And the end result in both instances is type two diabetes and hypertension and cardiovascular diseases. So there're actually two ways to view the epidemic of non-communicable diseases. And one is western lifestyle. The other is what you were exposed to in early life. So what can we do about it? Never give up. I wrote a small paper on this in Science last year. Where I said: "Duble burden of noncommunicable and infection diseases in developing countries. We have malnutrition and infection in early life. And we now know that it increases the risk for chronic incidence in later life. We have diabetes and tuberculosis interacting". Maybe the time has come to start to work together and not divide ourselves into infectious diseases, non-communicable diseases, high income countries, low income countries. Because we are all part of the same world. I think we will have to have a life course thinking on global health. Here is a picture from a wall in Copenhagen, where I'm working. You'll see we have been very much focusing on child, motherhood, not so much on old age and so on. But we should recall that premature aging, type 2 diabetes, cardiovascular diseases that would be normally relate to old age they are not going to be a disease of old age in developing countries and low income countries. They will hit you when you are 30 and 40. And therefore do more to children and maternal healthy but don't forget to do something to adult health as well. So thank you very much for listening to these aspects of global health risks, determinants, non-communicable, communicable diseases. They work together, we should work together. Otherwise we're not going to improve health and combat disease globally. Thank you very much.
