[MUSIC] Many people exercise and take medicine to fight being overweight in order to delay or treat type two diabetes. Sadly it seems that in most cases people regain weight and thus retain their increasing blood glucose levels. So why is this? The answer might be quite simple, as a significant part of the explanation is that the hormones circulating in our bloodstream tells us to consume the same amount of calories as we did before we lost weight. Or in other words mechanisms in the body that regulate appetite will fight against the new and low weight. And keep begging us to get back to our former overweight self. Eventually people simply give up this fight against the bodies greedy appetite and regain weight. Controlling the appetite seems to be the key, but currently we only have one therapy that shows significantly better results compared to both exercise and medicine, and that is gastric bypass surgery in which a part of the stomach is removed. Professor Jens Juul Holst has completed several studies on people who've had gastric bypass surgery. So let's ask him to explain the concept. So how does that work? >> Yeah, that is a very good question that has kept a number of people very busy during the last 20-30 years. And particularly since it was found out that if you have diabetes and have gastric bypass surgery, your diabetes will go away. That made it extremely interesting to find out what is really going on here. So when it was conceived the operation, it was thought that the fact that you cut away most of the stomach and leave a very very small pouch of 30 milliliters or so, that that was a restrictive element, you couldn't eat as much because the stomach was so small. And secondly because you then continue from that little pouch down to a place about halfway down the small intestine. You bypass a large section of the upper, small intestine of the stomach. And that must lead to some malabsorption, it was thought. But it turns out that it is not restrictive at all. It doesn't represent any hindrance for food to enter the GI tract and there's no malabsorption at all. So, that was not the mechanism. Although, this was what more or less was the idea. What turns out is, that people lose appetite to a certain extent and eat less. And this is why they lose weight. And that is a very nice explanation, a really, really, that's the nice way to do it because that's what you should do. That's what we've been asking them to do all the time, eat less and lose weight.. >> Why do they lose their appetite? >> And that's where it turns out that a number of things may happen. And the thing we have focused on in our own research is really some of the hormones from the gut. And we have a set of hormones from the gut that regulate appetite normally. And some of these hormones from the gut, they're very potent and they inhibit appetite, that's when you have had a meal. They're secreted, and then you feel satiated and then you eat less of course. And these hormones are tremendously upregulated after the operation, it turns out. It seems that getting the food down there at the distal half of the small intestine makes these hormones go berserk and produce a lot of it and send a very strong signal to the brain that you shouldn't eat as much and then you don't eat as much and then you lose the weight. So that is probably a major mechanism here. >> Why does the diabetes disappear? >> What happens is if you do lose weight, you can cure certain forms of type two diabetes, particularly if they're not too pronounced. So that helps a lot. But in addition one of these hormones that regulate the appetite also stimulates insulin secretion to a very large extent. So you get both an inhibition of food intake and a stimulation of insulin secretion. And that then keeps your glucose down, and then, the diabetes is gone. You eat less, lose weight, improve your insulin sensitivity because that happens when you lose weight, you improve your diabetes, improve your metabolism, and that's it. >> The only thing is, is the ethical question then, because your actually having surgery on a healthy organ to, >> Yeah. >> Cut it away? >> I've thought about it a couple of times. And it more just corresponds, doesn't it, to if you have a genital disease, and then you cure it by cutting of the genitals right? That would be a terrible thing. And it is more or less the same, you do with this kind of surgery. So, yes, you're absolutely right. But the problem is, we must not forget that having obesity and diabetes is terribly risky. So you have a tremendously elevated risk of dying and getting complications. And that's the real problem. So will we look at people just die and develop complications without doing anything? That's what we're really talking about here. So it's been demonstrated several times that with this operation, you can lower the mortality rates by up to 50%. >> These extremely good results that Jens Holst mentions, include several large scale studies where thousands of participants compared the effects of gastric bypass surgery on body weight and glucose levels. And the conclusions were clear. In the long term, gastric bypass surgery works. But like everything, it comes at a cost and for gastric bypass surgery, this include side effects such as nausea, dumping syndrome, hypoglycemia and much more. That said, the mortality rate declines and most people with type two diabetes who have a gastric bypass surgery continue their lives with no complications and even report increased quality of life. Most will within 24 hours of having the operation no longer need their medication. And within a few months almost all will have lost 30 to 40% of their body weight. Why then is gastric bypass not the standard recommendation treatment for all overweight or obese people with diabetes? >> So this is a complicated question because there's no doubt that the number of people with morbid obesity around the world greatly exceeds any capacity one can imagine for doing this surgery. So, there's completely inequality here. You can't solve the problem that way and that is obvious. So it's reserved for societies that organize this. I must say that in some countries they do it. I mean, they really go for it in some South American countries, for instance, and in China. They do this because they realize that this is probably the simplest way of solving the problem. It's also been inferred that it's expensive. But that is not quite true because given that it's successful and helps the way it's ought to do, it is also cost-effective. This has been looked at in several studies. So, the economic argument doesn't really fit in here. The problem is to organize it, it's the infrastructure that is required to do this. In addition, I must admit that I cannot image [LAUGH] a large part of the population having surgery for something which is really a more or less natural phenomenon. So there are some problems here. Now we should continue our work to try to see if we can think of something else to do than doing surgery. But in the mean time for those that really suffer, that have an early diabetes and morbid obesity, it is a good therapy, it's the best actually. >> What new questions has your work on gastric bypass raised? >> Yeah, so the first question was of course to try to find out what is going on here because if you know the answer to this and we think we have a fairly good idea about it, then you could probably also devise other methods of treating type two diabetes and obesity. And so we've been very interested in these hormones that are released from the gut that regulate the appetite and also that regulate insulin secretion. And we hope that we can understand that we can do one of two things. Perhaps we can make a mixture of these hormones, the right mixture the one that is actually that is elicited by the surgical procedure. And then give it to people and get the same effect. And that is something that many people are working on and I think it has a potential. I think it has a good potential. I think there will be medication one day where you get most of the effects of what you have with surgery and that you can then take. It will probably be expensive also. >> So what you're saying is one day, instead of having this surgery, we'll be able to have medication instead. >> Yeah, I think so. I think so. I think it will be possible. There's several groups working very very hard on this, including our own. >> Other researchers share Jens Holst's optimism regarding new treatment for the future. And a lot is being done to develop so-called medical gastric bypass interventions. A medical gastric bypass intervention does not imply surgery. And the hope is, the more knowledge about the underlying mechanisms of gastric bypass surgery will bring about new non-surgical treatments which will circumvent the major side effects and risks connected to having surgery. But how far are we regarding this research? Let us find out from one of the world's leading scientists in medical gastric bypass research, Professor Steve Bloom. We've had a discussion with professor Holst about surgery, gastric bypass surgery. Now is there any alternative to this? >> So surgery is amazingly effective and my colleague Jens Holst has worked on the way in which it works for a long time. Actually we've also, like him, worked on why it works and how it works, and it turns out that it's a lot to do with hormones coming from the intestine. We call them gut hormones. And the bypass causes them to be released in much larger amounts. They switch off your appetite. And actually, if you eat a meal, the reason you are less hungry after the meal, surprisingly, is that your gut has released more of these hormones and they switch off your appetite. But in the bypass it's as if you've eaten a meal all the time, because the food is sent further down the gut, that's what the bypass is doing. And because of that you have these high levels of, we can give them a name, satiety hormones. And therefore, you don't feel as hungry. Now, supposing we invent a medical treatment in which we give injections of these hormones without the need for the surgery. Most of us would rather not have the surgery, especially as it's slightly dangerous. And we'd much rather have a treatment which didn't need it. At least we could test how the hormones worked. So we're working on that way forward, as indeed is my colleague, Jens Holst. >> How would a medical gastric bypass work? >> A medical gastric bypass is not of course surgery at all, so there is no bypass, but it produces the same effect, i.e. by injection of the hormones, and hopefully it's a tiny injection once a week, have the hormones raised all the time just as you would have, had you had that surgery. And since the surgery worked through the satiety hormones, this does the trick just as well. And while we haven't yet got permission to do the trials in humans, we've certainly tested this principle in animals, and they lose weight and their diabetes goes away and it really works very well, actually even better than the surgery. So I'd rather not have the surgery, I'd rather have the medical treatment. >> In some countries, there is gastric bypass surgery implemented right now. So that is happening. Are you saying that we're moving away from that? >> Gastric bypass surgery is a very successful procedure. After it, people live longer and stay thinner and their diabetes usually goes away. So I wouldn't criticize surgery. I think it's nice to have an alternative. Some people are surgical risks, they have breathing problems or heart problems, and to have a medical alternative is a good idea. If the medical alternative produces an even better weight loss, then it may be that some people will go for it in preference. But we haven't got there yet, we're still developing the medical treatment. So if you were overweight today with diabetes, I'd go for the surgery. But I'd choose a good surgeon because I wouldn't want the risk. >> According to Steve Bloom, it sounds like this treatment has a bright future. Let's take a closer look on how this new hormone treatment differs from for example, incretin which is a hormone based therapy treatment that is already on the market today. And how this future treatment will be given to patients. And, this mind you means, hospital outpatients and not patients in controlled clinical trial settings. >> For the last ten years or so, what we've been trying to do is mimic what happens after bariatric surgery in terms of the hormone levels. We know that after bariatric surgery some of the gut hormones are elevated. One of the hormones is already available and is used by millions of diabetes patients, called GLP1. This hormone increases insulin secretion when you eat, and also signals to the brain to say you're full, less hungry and therefore people eat less. As a result it's one of the diabetes drugs that actually leads to some weight loss. But the weight reduction is not adequate, because at most you get just around eight kilograms weight loss. And if you think about the obese diabetic patient, this is not sufficient. What we've been working on is how to deliver GLP1 which is a drug which I just mentioned in combination with the other hormones that are elevated. So we currently also working on a hormone peptide YY and oxyntomodulin. And, what we've been able to do is to deliver all three hormones through a insulin pump and this is delivered through a subcutaneous root. So basically under the skin, okay. So you're not using a drip, but you're wearing a pump that delivers the hormone under the skin. And what we've shown is that with the infusion of these hormones, patients are less hungry. The glucose control has improved. And it's exciting because I think this is the first time we've been able to deliver all three hormones in an ambulatory patient. >> Will there ever be a cure for diabetes? >> We're still long way off from this, but certainly the one treatment that can cure diabetes is bariatric surgery. So technically we have a cure for diabetes, but surgery is not for everyone. And the surgery does not cure the diabetes in all patients either. Only a portion of patients are cured from the diabetes following surgery. And the procedure, itself, has risk and complications. [MUSIC]
