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Freed: This is Steve Freed with Diabetes in Control. We are here at the American Diabetes Association 77th Scientific Sessions, 2017. We are here to present to you some really exciting interviews with some of the top endos from all across the world. We have with us a very special guest, who is also presenting here, Jamie Uribarri. Did I get that right?
Freed: I get 10 points for that.
Freed: We can start off by you telling our audience a little bit about yourself, ADA must appreciate what you do.
Uribarri: I got my medical degree in Chile but I have been in the United States in New York at the Mount Sinai School of Medicine for many years. For many years, we have been involved in the study of these compounds in food, Advanced Glycation Endproducts, that I call AGEs as an abbreviation and how they affect health and how they may cause diseases. That has been the main reason of my research over the past few years. I’m also a practicing physician; I am a nephrologist and I deal with kidney diseases and that’s my interaction with diabetes. As you know, about 1/3 of the diabetic patients will end up with kidney disease, and most of these will end up on dialysis, and therefore, that is my interaction with the diabetes world.
Freed: So the title of your symposium is: “Healthy Lifestyle Matters for People with Diabetes and Kidney Disease: Finding the Good and Avoiding the Bad Food Choices for Patients with Diabetes and Kidney Disease.” Is there a short title?
Uribarri: (Laughing) That’s a very long title. But “Healthy Lifestyles” I would say, and “How to Live Healthy.”
Freed: We hear a lot about AGEs in our foods that we eat. Maybe you can give us an idea into that? The way I like to put it is, the sign of a good speaker is someone who presents ideas and concepts and then when people leave, they take that knowledge and they use it in their practice the next day. If you’re a presenter and you have beautiful slides but no one remembers anything when they walk out the door, then it is a waste of time for everybody. So what do you want them to take away from your presentation?
Uribarri: Well, most physicians are very well aware of these compounds, the AGEs that I call them, in relation to hyperglycemia. We know that if you have high glucose that is going to react with the three amino groups of protein and through a series of complicated chemical reactions, is going to form these AGEs. That has been known for many decades. Many people accept that most of the complications that we observe in diabetes over the long-term, are related to these compounds. But today we are talking about the AGEs that come from the food – food contains AGEs. When you cook food with application of high levels of heat under dry conditions, you may generate large amounts of AGEs. Although only a fraction of them are absorbed, indeed, that may be important, and they clear into the body, they get together with endogenously generated AGEs, and they lead to oxidative distress and inflammation, which eventually, cause disease. So over the years, we have shown significant amount of work in trying to demonstrate that if you take a diabetic patient, for example, or somebody with chronic kidney disease and you randomize them either into high AGE diet or low AGE diet, when people follow the low AGE diet, they have a significant reduction of inflammation, less oxidative distress and we have even shown that we are able to reduce insulin resistance as assessed by the so-called HOMA Index. So this is very significant and we believe strongly that a high AGE diet is a factor-causing disease and, more importantly, going into a restricted AGE diet actually can prevent the development or the manifestation of disease.
Freed: Have we seen studies to show that result?
Uribarri: Yes, we have presented literature in 2002, many studies in important journals such as the PNAS, Diabetes, and so on and so forth. The first study that we presented was when we took a group of diabetes patients and randomized them into either a high AGE diet or a low AGE diet and the foods were prepared for them in our clinical research center. The participants came and picked them up twice a week and at the end of a period of observation of about 6 weeks, we were able then to show marked decrease in the markers of inflammation and oxidative distress. And then after that, we have repeated other people with diabetes and insulin resistance; we have been able to repeat that in patients with metabolic syndrome in which case with a study of over one year. And of course in this case, the patient prepared their own food at home and with very detailed guidance by the study dietician that kept calling them twice a week and face-to-face interviews like once a month or every two months. The findings are remarkably uniform. The low AGE diet brings down the levels of the AGEs in the circulation, but more importantly, that seems to be associated with decrease in markers of oxidative distress, inflammation, C-reactive protein (CRP), TNF alpha, and in the case of diabetic patients with insulin resistance, we bring down the HOMA Index. This has been reproduced by a couple of people in other countries such as in Mexico, Denmark, Australia, and France. So we believe that this is serious and we just want to continue in larger number of people to demonstrate that the study can be reproduced.
Freed: You mention high AGE diet and low AGE diet. Obviously it’s healthier to do a low AGE diet, but give us an example of the foods we shouldn’t be eating which you would consider a high AGE diet.
Uribarri: So the beginning of our research, we measure the content of AGEs in a variety of food. Again, the most important concept in this sense is the way the food is cooked. So if I take a dietary history and I know what food you eat and how much, that allows me to calculate nutrients like protein, carbohydrate, caloric intake, fat, and so on and so forth. But if I know the way the food is cooked then I can determine the AGEs. The idea is the following: take for example, three pieces of chicken the same size, leave one raw, another one, boil it, and another one, broil it, and then you homogenize each one of them and measure the content of AGEs. The content of AGEs increases, progressively, from the raw to the boil to the broil. So that gives us the clues of what to eat and what not to eat. So I take a dietary history from you and you like this kind of food, for example, meat in a certain way, and if you are preparing it normally like grilling it, I would advise you to poach it, and so on and so forth. So it is the way in which you cook.
Freed: That’s interesting. So you mentioned raw foods, then you mentioned slightly cooking it, or boiling it, but that tells me that you don’t want to overcook foods; that seems to be causing more AGEs. So you didn’t mention chicken on the grill, is that the worst?
Uribarri: Yes that’s bad and fried chicken too.
Freed: So if you fry it or grill it outside on a charcoal grill, that’s actually going to increase it more?
Freed: So how do you make your steaks?
Uribarri: Well, number one, I like steak, but I don’t eat steak very often. One way, for example, that you can decrease the formation of AGEs when you are cooking is by bringing down the pH of the solution. So marinat[ing] it, for example, with lemon vinegar before preparation actually decreases the formation of AGEs and there are some other tricks of that sort. So what is important is that we are not saying low protein, low carbohydrate, and low fat. And we are not saying raw by any means. We are saying that you can eat whatever you want, but just cook it in a different way. I say eat whatever you want, but pay attention to portion and size, and try to eat low AGE and add as much fruit and vegetables as possible and try to eat fresh and unprocessed foods. That creates a healthy lifestyle.
Freed: So, for example, if I cook asparagus on the grill, is that going to have AGEs?
Uribarri: Yes. But there’s a remarkable difference if you look at our database, for example, between plants that are heated and animal protein that is heated. So if you take steak with a lot of fat on it, you are going to generate a lot of AGEs. If you take a plant and you heat it, you’re going to increase the amount of AGE but not proportionately. It’s not the same kind of influence. Influence is much less, if you cook your veggies you have raised the AGE content much less than if you cook a piece of steak.
Freed: I don’t want this to be a cooking class.
Uribarri: (Laughing) I’m not a chef!
Freed: We tell patients to stay away from anything white, stay away from anything red, don’t eat the pizza, and don’t eat the pasta. All those different things and now you’re coming along and saying well it’s not just the carbs, it’s how you cook your food. So that’s something else now we have to show patients. Sometimes I think we overload patients with too much information. So how do you get this information across as to better ways to cook your foods? What do you tell your patients?
Uribarri: Well we have a dietician that helps us because they know how to approach patients and they know how to use the right words, and they know how to tell them in terms of the kitchen and all of that. I’m not very good at that, I am not a cook.
Freed: So your educators are trained to talk about this.
Uribarri: Absolutely. That becomes very, very important. Without that, this doesn’t work. And all the trials that we have done has been a very painful process because, for example, most of this has been done in New York City, in Manhattan, in Spanish Harlem where the population of patients is very used to grilled chicken and foods of that sort. To explain to them and to make sure that they sustain a diet and change the way they cook over the long-term, it becomes very, very difficult. So clearly, yes, I understand perfectly well the concept that you can overload the patient. But that’s why at the end, I said earlier, that just a few things are important. You can eat things but do not overdo it with portion size.
Freed: I kind of get the idea that cooking food over an open flame, doesn’t make any difference what the food is pretty much, that you are going to increase the AGEs.
Uribarri: Yes, you’re going to increase, but again, as I said before, if you have a small amount of cauliflower and you put it on the oven, the increase in AGE will be, just to give you a number, plus 20. If now you take a very fat steak and you put it on the grill for the next 10 mins, you may increase (AGEs) plus 20,000. That is the magnitude that you have to apply. That is why you have to know the content with the different food items depending on the way they cook. That is where an educator, a dietician, is important.
Freed: Are there things that we can do such as physical exercise that can help reduce this?
Uribarri: You know, there is some controversial information in the literature in terms of the effect of exercise on AGEs. But there is no doubt that exercise is part of a healthy lifestyle. So you always have to put together a good diet with a good exercise program – they have to go together.
Freed: So it’s more about what you’re cooking, but are there any foods that are higher risk for producing these AGEs?
Uribarri: Clearly the food of animal origin, meats.
Freed: So that would be fish also?
Uribarri: Fish but much less. For example, you take a piece of a poached salmon and the amount of AGEs is much less than what you would find with a grilled steak.
Freed: So when you see a patient, most of the time you don’t have the time to discuss those things with them, you send them to a dietician and those people will discuss it and tell them how to work their nutrition to get less.
Uribarri: Exactly, our dieticians, however, have been trained in this low AGE way of cooking. So they pay much more importance to the way a patient cooks rather than giving them precise information in terms of protein, carbohydrate, or lipid intake.
Freed: Do you find that there is more in more types of ethnic cooking?
Uribarri: Yes, absolutely. Minorities, clearly. I don’t want to be very precise, but clearly, yes, that is the case.
Freed: And yet, I don’t see that in the ADA Standards of Care. When it comes to cooking, where would I find that, in their literature?
Uribarri: You don’t find it. That’s why we are very surprised that we have been published since 2002 and this has never been incorporated. It plays a tremendous importance, I believe, in terms of the effects of diabetes for minorities and other groups, the way they eat and the way they cook.
Freed: That’s interesting because there’s discussion that there is no such thing as weather change and climate change from some part of the medical community, some say there is and some say there isn’t. Would you put that in the same class as there are some people that agree and there are some people that don’t agree? Or is it that nobody cares?
Uribarri: It’s a combination of lack of agreement, like anything; when you put a hundred physicians in a room they will not agree about anything, but it is also the point that most people do not care. When you are talking to physicians, in general, they get bored when you start talking about diet because we have been trained in medical school to give medication. When a patient complains, apply a pill. And at the end, for example, when I go to the renal clinic, patients come with a bag of 10, 15 or 20 different pills that they don’t understand why they are taking. Physicians are much more comfortable prescribing a medication than saying exercise and go into a low AGE diet. So it is a matter, I believe, of not 100 percent agreement but also that fact that most physicians do not care too much. That is why I try to influence more dieticians, nutritionists, and people who participate in the general care; they are more attuned into this.
Freed: Well this isn’t just for diabetes, though.
Uribarri: Absolutely not. I mean my main field, I am a nephrologist as I told you in the beginning. So kidney disease and I deal with dialysis. And it is also for the general population if you want to live healthy.
Freed: Being a nephrologist, do you see that it plays a major role in kidney function, especially for people with diabetes who are at risk for kidney failure?
Uribarri: Absolutely. That is why the majority of those patients die, if they don’t end up in dialysis, they die from cardiovascular disease. Take a patient with diabetes and CKD, and that is a combination for cardiovascular disease for almost certain over the next few years. That is why I am involved in this area because it touches very much into what I do on a daily basis. And of course, I am convinced that this is the story. As you know, if you are not convinced that what you do is important, why should I be doing it?
Freed: Is there a way to measure this?
Uribarri: Well, that complicates the issue because, of course, and we do measure it. There are different ways to measure it. There are some… mass spectrometry, which are a little bit more complicated. But the problem is that all of these still remain in the realm of research that no commercial laboratory will do it. So, no, if a practicing physician wants to measure AGE in a clinic, it would not be possible right now. That complicates the issue a bit and second, there are many AGEs, so you have to know which compound action you are measuring. So whenever I give results, I go into the description of the method that we use to measure and what compounds we actually measure.
Freed: So if there are drugs out there that we know that can reduce inflammation would that be a benefit to the patient?
Uribarri: Yes, they should be, but again, any time that you act with a drug, you have to test it. You have to do clinical trials and have to put the drug versus the placebo or control agent and see what the effect would be on AGEs and on outcome. The problems is that you know , to prove things, we have done this very well-regulated in terms of high AGE vs. low AGE. But what is the population that we do in our trials? We take a group of 20-30 diabetic patients and randomize them. So it is a relatively small number of people. We follow them for how long? For a few months. It is a relatively small number of patients. So therefore, we can only use small models. To see real outcomes, you need to take a very large number of people and follow them for very prolonged periods of time. But that is something that requires a lot of money. We just don’t have it and it is unlikely that we are going to have it in the near future.
Freed: Well, obviously, we’re looking for money for kidney failure, for A1C reduction, and for hypertension. It reaches a point where like you said, if you are lower on the food scale, it’s more difficult to generate income especially from NIH when they are cutting funds. That puts you really at the bottom of the list. So I imagine it’s very frustrating for you not to be able to do some of the studies that you would like to do.
Uribarri: Yes, absolutely, that is a significant limitation.
Freed: So are there any medications? Because we have medications to reduce inflammation. I know statins can reduce inflammation. If we can’t measure it, we really don’t know if the medication is going to reduce that. So how do you manage that?
Uribarri: No, we can only extrapolate from studies. For example, metformin, a commonly used drug now for the treatment of diabetes has been shown independently that it reduces the levels of AGEs. So that is based on more experimental studies. So based on that, I am assuming that every time a patient is taking metformin, other factors are being caused independent of the degree of glucose reduction that helps to reduce AGEs, and therefore, inflammation and oxidative distress. But there are no trials where metformin vs. placebo had been done with measurement of all these factors.
Freed: What are some of the other things? It increases your risk for cardiovascular disease because of the inflammation, it increases your risk for kidney disease. What are some of the other things that it increases your risk for?
Uribarri: Well, hypertension is a very, very important factor and that is something that we are always paying attention to. Every time that a patient comes to me with kidney disease related to diabetes, I said, “Please realize that we do not have a specific drug to cure this, we can only approach the problem.” The main two factors for you to do to at least slow down the worsening of disease are tight control of blood sugar and tight control of blood pressure. So paying attention to blood pressure is very, very important.
Freed: Well, being in the field, being a kidney specialist, do you see a lot of patients that go on dialysis?
Freed: I know from personal experience with family members, that it really takes away your life. Three days a week you’re in the clinic and then it takes you a day to recover and that leaves you one day a week to live. So it’s really a traumatic thing. And just out of curiosity, from your knowledge, technology is changing everything we do on a daily basis. Here you are seeing all the new technology, things that you would never think of. You call for Uber and a car pulls up and there is nobody in the driver’s seat and it says, “Welcome doctor, jump in, we will take you where you want to go.” So when it comes to dialysis, it’s expensive, it’s usually done at a clinic, are they doing things to miniaturize that and make it more acceptable for patients and that it won’t destroy their lives?
Uribarri: Yes and no. There have been attempts but very slowly moving. There’s a tremendous disproportion between the facts that you were mentioning, we go to the moon, we do a lot of fantastic things, but the basic technology of dialysis remains the same: very primitive and very limited for the patient. What I can tell you is that there are some attempts to do that. Part of that interest is that dialysis is paid by the government, which is good, but on the other hand, because it is a fixed payment, there’s not that much financial incentive for companies to develop new things. But I don’t want to go into those financial issues. In reality, in dialysis, there are some improvement. The machine for now, for example, we tend to push a lot for home hemodialysis and the machine is extremely compact and they can be fit in a corner at home. I do a lot of peritoneal dialysis, for example, and it has had tremendous advances. We have a new machine now that is very small, very compact and does all the therapy at night time and leaves the patient kind of free during the day time. So for people who are very motivated and like to self-care, there are some advances, but I grant you that they are baby steps. I would like to see much more.
Freed: If you had to put a number on your patients, of ones that could have been prevented, what percentage of kidney disease would you say can be prevented?
Uribarri: Oh you’re asking the wrong person. I would tell you all of them, no, but if you look at information for dialysis, we have a lot of information in this country because we have a database, the USRDS Database. It has information for every dialysis patient in this country. Sixty percent of those patients, patients who are on dialysis in this country right now, it is either because of diabetes or hypertension. In theory, this can be prevented. Take into consideration that when we talk about diabetes, we are not talking about type 1, which is minute. I do not mean to diminish type 1 and what it means for families that are affected by the disease, but from a public health perspective, it’s a minor problem. It is type 2 that is the one that is important. And that is clearly a socioeconomic disease. It has nothing to do more with than with lifestyle; you eat wrongly, you do not exercise, and all of that can be affected just by lifestyle modification. So it is really a shame that in terms of diabetes and hypertension, we’re just acting with medication to correct some specific problems and not preventing the development of the disease itself. So if I am basing the statement on the fact that 60 percent of the patients on dialysis in this country are on it solely because of diabetes and hypertension, I would say that at least 55 percent could have been prevented.
Freed: Why don’t we just give everyone SGLT2s?
Uribarri: Well, we should perhaps start doing that, no, there’s more than that, and you need to go healthy all the way. Drink water, don’t drink soda, go on low AGE diet, eat fresh fruit, unprocessed foods, try to not add too much salt, add a lot of spices, exercise, at least walk daily, and then, if you still need medication, take metformin and SGLT2s. That may end up to be the answer.
Freed: Well, I want to thank you for your time. I found it very interesting. I learned something and that’s one of the reasons I like to do these interviews. Not for our readers, just for myself, because I get to learn from all the top doctors in the world at the forefront of making changes in how we practice medicine. So I want to thank you for that.
Uribarri: Thank you very much for having me.