The type 5 diabetes story

[MUSIC] Hello and welcome to another episode of Detalk, the podcast series of the International Diabetes Federation that explores innovations, insights, and challenges in diabetes care worldwide. On your host, Dr. Felicit DeRose. In this episode, we're going to learn more about a new diabetes classification, type 5 diabetes. While most people are familiar with type 1, type 2, and gestational diabetes, diabetes is more complex than this limited classification. Previously known as malnutrition-related diabetes, or MRDM, type 5 diabetes has been on the radar for at least 70 years, but was only formally classified in January this year. Following this recognition, the International Diabetes Federation has established a type 5 diabetes working group that will develop formal diagnostic criteria and therapeutic guidelines for this type of diabetes. So what exactly is type 5 diabetes? How is it diagnosed? And why doesn't matter? In this episode, we'll look at the distinct pathophysiology of a condition that affects 20 to 25 million people, mainly in low and middle income countries, in South Asia, and sub-Saharan Africa. Joining me today are the chairs of the type 5 diabetes working group, Dr. Meredith Hawkins, and the co-chair, Dr. Nehal Thomas. Dr. Hawkins is an endocrinologist and the founding director of the Global Diabetes Institute at the Albert Einstein College of Medicine in New York. She is a leading expert in global diabetes and metabolic research and the interplay between under-nutrition and diabetes, particularly in low-resourced settings. Dr. Thomas is the endocrinologist and professor at Christian Medical College, CMC, Valnor, India. With a career spanning clinical care, education, and research, Dr. Thomas has been a key collaborator in global research initiatives, exploring the intersection of nutrition, metabolic disorders, and public health. Welcome and thank you both for joining me today on Detox. It's great to have you both with us. Thank you. Melissa, it's great to be here as well. Thank you for the stood. What a wonderful experience. Thank you so much. The concept of type 5 diabetes refers to an atypical form of diabetes that occurs in lean under-nutrition individuals, which is characterized by marked insulin deficiency and poor metabolic control. Although type 5 has been observed for at least 70 years, it has been largely overlooked in global health discussions. The condition was first noted in the mid-20th century and often misclassified as type 1 or type 2 diabetes. Previously, prevailing theory suggested that the condition developed due to insulin resistance, but recent studies suggest that it is due to deficits in insulin suppression. In recent years, renowned research led by Dr. Hawkins and Dr. Thomas has confirmed its distinct metabolic profile. Let's start with you, Dr. Hawkins. You have been instrumental in advancing our understanding of type 5 diabetes. Before we get into the clinical details, I'd love to know a little about your journey in the classification of type 5 diabetes. Where did it all start? It was actually 20 years ago that I personally became familiar with this condition. That was first when I was teaching at global health conferences and many people would come and ask me, these people from northern tribal areas of India, people in rural Afghanistan, people from many countries in Sub-Saharan Africa, etc. And they come to me and say that they were seeing a lot of very lean patients with diabetes that did not seem to be type 1 diabetes. And then, doing thereafter, I was actually teaching at a medical school hospital in Uganda, in the Lago hospital, where I was seeing both teenagers as well as adults who were very thin and undernourished, but lacked completely the features that we associate with type 1 diabetes, the diabetic ketoacidosis, the Christmas, breathing, all those classic features. These individuals seem to have had diabetes for a while because when they came in, they were dehydrated, they had very high blood sugar levels, but they did not come in with ketoacidosis. And because they were so thin, they certainly didn't look like type 2 diabetes. It was at that point, because I couldn't find anything about this in Western textbooks, I went back to the literature, the World Diabetes Literature, and I discovered that 70 years ago when Jamaican, and a stupid clinician noted that some of his patients, just as I had noted, but some of his patients failed to fall under the classifications of type 1 or type 2, and for similar reasons that they were young and lean, but didn't have ketoacidosis, and they were remarkably malnourished. Another feature was that they had no fight in their liver on biopsies unlike type 2. So when this report was published in the Lancet in 1955, immediately gained the name of Jamaica, or day-type diabetes, but only kept that name briefly, because immediately thereafter, similar cases were being described in many tropical low and middle and income countries, including East Pakistan, which is now Bangladesh, Indonesia, India, Ethiopia, and many countries in Sub-Saharan Africa. Now with the quantity of reports that were coming out about this, this gained the attention of the World Health Organization, who adopted the classification of malnutrition-related diabetes in 1985. However, in 1999, this classification was removed, because a pall of experts met and expressed the concern that there was insufficient evidence to link malnutrition with diabetes. However, in the intervening 26 years, this condition did not go away, and neither did undernutrition on a global basis. Unfortunately, it's remained at a plateau level over what a billion people around the world. And it's noteworthy that many researchers around the world continue to publish reports of similar patients. Now, once I became personally involved in studying these individuals, because my background is performing in-depth metabolic studies in humans, I needed to find a place where we could do the type of research that the WHO said was required, because we had to investigate if this really was a unique form of diabetes. This was what took me to Christian medical college in Valor, India, which is an incredible place. It would train our medical institution with a phenomenal research background. And so this developed into a very ambitious 10-year research project in which my team devised a protocol based on our own expertise and very carefully trained and oversaw these studies. And I would commend Professor Nehaal and his team for working together with us. We were able to execute a studies that would be done in very few places in the world and to my knowledge, nowhere else at a low and middle income country. So basically, we were able to study individuals with this type of diabetes, compare them with type 1 and type 2 diabetes. And I would also say that we carefully excluded all other known forms of diabetes. So this came to fruition. We had a publication of diabetes care in 2022, that thankfully, which read by many people around the world, this broadest-in-duck contact with a number of investigators would have been studying this in many places. And so this January, Professor Nehaal and his team hosted a spectacular consensus meeting in India. This was attended by many people around the world who'd been researching this condition. And then, by many experts in the field who facilitated in-depth discussions, this concluded with a consensus in which all participants voted, that this should be a unique classification of diabetes. And this consensus statement is now about to be published in Lancet Global Health. Importantly, it was at this meeting that Professor Peter Schwartz, president of IDF, proposed the classification of type 5 diabetes. And this then made this form of diabetes distinct from all other known forms of diabetes. - Wow, thanks so much for sharing that information, giving us that history, I had no idea. And then just think about Jamaica, 1955, like how long this has been around in no DKA. I have to say, as a person that was diagnosed because of DKA, I'm just stunned. Not just in terms of scientific discovery, but also in responding to real clinical challenges that were being overlooked. [BLANK_AUDIO] powerful to hear how your work connected the dots between global health observations and a whole new way of understanding diabetes. And the fact that it led to the creation of the Global Diabetes Institute really shows the scale and importance of this issue. Now starting with the basics. Type 5 diabetes is now an official classification. Dr. Hawkins, can you explain how type 5 diabetes differs from type 1 and type 2 diabetes? This is such an important question. Because what we now call type 5 diabetes, these individuals have been lean and malnourished throughout their development. And often when they have presented with diabetes, they often show some signs of stunting. Now they differ from type 1 diabetes because although they can be both groups can be young and lean. But the key point here is that the degree of under nutrition in type 5 makes them quite distinct. The other key point, as I mentioned in my own observations, was that they do not tend to develop ketoacidosis, even if they were it might be very mild. And so that means that they don't require insulin survive. Many of the young people that I met in Uganda could be off insulin for months. And although that would make them dehydrated with high glucose levels, they still wouldn't go into ketoacidosis. So that helps to show us how distinct it is type 1. Now they differ from type 2. First of all, because they have such remarkably low BMI's in the tens of our studies, we've found quite an important and slightly point at 18.5. So a lot of these people are less than 18.5. When we study them very carefully using MRI machines, we found that they really did not have much at all in the way of fat scores. So for example, very little visceral thigh, no fat in their liver. And the other thing is that because their severe metabolic defect is an insulin suppression, they're not insulin resistant like type 2. So that also makes them very distinct from type 2. But before concluding, I need to briefly mention type 3 and type 4 because everyone always asks, what's type 3 and 4? So type 3 had been artificially claimed as Alzheimer's associated diabetes. And subsequently, what's now called type 3c has been officially recognized by the American Diabetes Association as pancreatitis associated diabetes. And more recently, type 4 has appeared in the literature as aging associated diabetes. And we're told that currently in Germany, type 4 is gestational diabetes. So it was very important and proposed by Peter Schwartz that there needed to be a classification that was completely distinct. So no one claims type 5 diabetes. And that gave us something very unique for our unique form of diabetes. My next question is for you, Dr. Thomas. We often hear about over-nutrition and obesity as drivers of diabetes. But in some parts of the world, the issue was quite the opposite. How is chronic under-nutrition, particularly during childhood or adolescence linked to the development of type 5 diabetes? I'd like you to first picture the common form of diabetes, that is type 2 diabetes, which is so very prevalent across the world. So disorder, which we know as far as the most common risk factors being that of too much over-nutrition and lack of physical activity. Besides the whole lot of other risk factors, which are there, including environment impollution, a kind of food that we eat, lack of fruits, more fruit juice rather than fruits, etc. Even smoking and alcohol have been attributed to worse, increasing risk. But there is one intersecting point between type 2 and type 5 diabetes. And that is low births weight. If an individual is born low birth weight, and this is linked to a hypothesis which was generated way back from the herfurt chart in 1989 by David Barker. It's called the Barker hypothesis. If one is born low birth weight, an individual after births, if exposed to over-nutrition, has an increased tendency to develop obesity, diabetes and hypertension at a relatively early age. This is called the thrifty phenotype hypothesis. An individual who is underweight has a tendency to accrue more fat, have more insulin resistance. And also in addition to that, might have some degree of beta cell dysfunction. So insulin production may be mildly reduced. But that is type 2 diabetes. Now imagine an individual who is exposed to antinatal under-nutrition. A mother during either a period of war or famine or just simple, low socioeconomic status where it may be an endemic problem, where people are exposed to core-nutrition all along. And that mother delivers a baby who is low birth weight, who has low beta cell function, no muscle mass and continually thereafter is exposed to under-nutrition. The child, the infant and the adolescent thereafter does not have adequate amount of protein and take in particular. And therefore, you have a double-hit under-nutrition in-utro and an under-nutrition after-deliver. This can subsequently lead to a more flora-ed beta cell dysfunction with more flora-ed insulin deficiency. Lack of muscle mass, which wherein glucose cannot be transferred into the periphery adequately. These individuals are not insulin resistant. In fact, they are exquisitely insulin sensitive. And that has been shown by the studies which Professor Meredith and us did at well-o. It has also been shown in studies in other parts of India and in Thailand, wherein individuals have beta cell dysfunction and also have exquisite insulin sensitivity. They are not insulin resistant. So this is the basic pathodemesis, a double-hit under-nutrition during pregnancy followed by under-nutrition in-infancy, childhood and maybe even in a dollocene. This has been shown by studies in Jamaica wherein babies who are born with merasmus actually have a history of low birth weight. And these merasmic babies, if they are given a glucose load, have a lack of production of insulin and have a tendency to have impaired glucose tolerance in early childhood. And this has been work done by Michael Boen from Jamaica. There are animal studies that in mice and rats and there are also studies and primates wherein research has been done and have shown quite clearly that protein under-nutrition specifically induces beta cell dysfunction, lack of production of insulin. So we have models right across the board from animals and the unfortunate situation of human beings are exposed to protein under-nutrition developing this problem. Structurally, the pancreas is normal when you imagine them. You do a CT scan or an ultrasound. They look pretty much normal. But the beta cells are dysfunctional and the insulin sensitivity is good. So this is basically the pathogenesis and the evolution of this particular condition. Thank you for sharing that. Now up until now, type 5 diabetes was not recognized in clinical guidelines as I mentioned in the opening. It's a reality of many 20 to 25 million people, especially in parts of the world where under-nutrition is still a major public health concern. Where is type 5 diabetes most common? You talked about Jamaica, you talked about India, where is it most common? And why is it often misdiagnosed or overlooked in clinical settings? So this form of disease that is under-nutrition associated diabetes is commonly found in tropical areas, particularly being deported more recently from sub-Saharan Africa. There are large numbers of patients who have been deported particularly in Ethiopia, Uganda, also from certain parts of India and South Asia in addition, they have been deported in significant numbers. And we do believe that they also exist in parts of South America. Now the question here is why has this condition been under-recognized? Now if you look back into the history and what Meredith has actually told you is that people plain and simple thought that in a situation of under-nutrition that patients with type 2 diabetes when uncontrolled were just losing a lot of weight. And these were just patients with type 2 diabetes who had poor sugar control and that was it. Another situation and because of diagnostic facilities being significantly less in these parts of the world, lack of antibody testing, etc. Some people said that these are patients with type 1 diabetes who have just not been recognized. They probably didn't take into account the fact that none of these patients had ketoacidosis. But we do know that not all patients with type 1 diabetes have ketoacidosis and perhaps so could these could be the case as well. So these were the two situations where people said that okay fine, there is no other condition is due to under nutrition and that type 1 and type 2 might explain all the these lean patients. Now, from another perspective, and this is from what we are thinking of today, even if we have to think about type 5 diabetes, we have to very carefully rule out other conditions. We should remember certainly in both the developing and the developed world that type on diabetes is an important cause for lean diabetes. And therefore, it is very important. And of course, you have a very important biological clue that diabetic ketoacetosis is present means that it is highly unlikely to be type 5 diabetes. So, you rule out type 1 diabetes in this situation. It is important therefore, to have antibody testing of at least one type easily available across even the developing world to make sure that we are ruling out type 1 diabetes at an early point of type. Another set of diseases and I think this is the second most important cause, particularly in tropical areas. There is a peculiar condition called fibrocalculous pancreatic diabetes. This is a condition which presents with lean individuals who have malapse option, steatory, fat malapse option and abdominal pain in their teens and early adulthood. They are associated with uncontrolled glucose levels. Day 2 do not have ketoacetosis. But the key factor here is that they have a structural defect in the pancreas. In the absence of alcohol intake, they have shrunken pancreas with duct dilutation and large stones within the ducts of the pancreas. The classical alcohol associated pancreatitis can also present with abdominal pain and steatory. But usually the calcification is spread in the pleine chimer of the pancreas. This is a very important condition. It is found also in the areas where type 5 diabetes has been reported and greater significance. It is also found in areas where there is a no-sourish economic status of people. But it prevails even in areas where they become middle and come subsequently. The key here is doing an ultrasound which may pick it up in 60% because the CT scan would help in diagnosing this better. So these are two important conditions. Besides these, there are genetic conditions, the monogenic beta cell dysfunction disorders. These usually have typical good family history. So if you draw a pedigree chart, you will find one side of the family at least having a huge cluster of individuals who have young ones in diabetes. Now type 5 diabetes usually does not run in families. It is not what we would say, autosomal dominant in inheritance pattern. Most patients with the monogenic beta cell dysfunction, what we call modi or even the extended ones that are ones beyond modi as well, are not as lean as these individuals. The classical description of a South Asian person who has this condition of type 5 diabetes would be a BMI less than 19 kg per meat spread. That is a classical description. Most monogenic disorders are not like this. There are certain forms of monogenic disorders, a few of them which have this condition. So that would be a little lower down on the list. And to remind you that monogenic disorders can occasionally present with what we call novel with the denovovarians without a family history and that can occasionally occur. HIV can be associated with a condition, the thinning of the body and with diabetes, especially if they are on anti-retroviral therapy. But this is more obvious to diagnose because they of course have a diagnosis which can be made underlying which is caused by the virus and they usually are insulin resistance. They have a lipodistrophic features, abnormal distribution of fat in the body and their C peptides are elevated. Another rare condition which is autosomal recessive is the congenital forms of diabetes which are very lean, congenital lipodistrophies. But these are much rarer than all the other conditions which I will describe. So that is the natural is how you think about the other conditions which may be misdiagnosed as type 5 and how you rule them out. And three tests which I would like to highlight which should be done even in the developing world include at least a pasting C peptide, maybe a gand antibody to rule out type 1 diabetes if they do not have ketoacidosis and an imaging of the pancreas at least an ultrasound if possible a CT scan. So that's my take on how you think about it broadly between type 5 and the other causes of lean diabetes. Thank you so much for that information. I now know three tests will help rule out some of those other kinds because I was also wondering about moody diabetes. So you answered that question for me as well. I'd like to now also ask you a question Dr. Hawkins. Is the condition also a risk in low resource settings in high income countries where food insecurity and economic marginalization exists? One thing I need to emphasize is that type 5 diabetes is associated with persistent lifelong under nutrition. So as Kess and you all mentioned it would be in utero these people would have low birth weight, throat childhood, the adulthood and in fact by the time we diagnose them they've never managed to gain weight. So these would be the individuals that we encounter in the low middle income countries. Yes of course at end year right you're so right by saying that in high income countries there can be food insecurity and there is. I actually work in the Bronx and this would be probably about the low zip code in terms of income in the country and so we do see food insecurity but we also unfortunately see obesity because they're in these food deserts as they're called the food that is available is often high, alloric dense and high carbohydrate etc. promoting more weight gain and so therefore we do see a different picture. We see the type 2 picture even even when there is the food insecurity and the high income settings but I do believe that we are seeing these individuals because in our clinics we're seeing a good representation now from people coming from many parts of the world, many low and middle income countries and yes indeed we are seeing many people with low BMI's even below 19, 18.5 and I do believe that many of these individuals likely have type 5 diabetes and we need to consider how to treat them as such. One other interesting point is that we do have a colleague in Japan who has noted that many of his women that he's treating with metabolic defects have very low BMI's volitionally because they want to be very thin but I would have to say that his careful investigations of his subject seem to show that they are quite insulin resistant which is not the case with type 5 diabetes so I would say at the moment I would answer this predominantly the people that are coming in from other places in the world that have had that chance to have persistent under nutrition throughout their whole life. Thank you for sharing that so if I understand correctly I'm just going to put it on my terms and you just help me understand when it comes to people in say high income countries that have poor nutrition but in fact there's a difference between malnutrition and poor nutrition versus lifelong undernutrition. Do I have that correct? You have that absolutely correct exactly so that they would be exposed by virtue of the fact that it seems around the world that what we would call the bad foods but in essence being the high calorie foods, low protein, high simple carbohydrate etc those always tend to be cheap wherever you are in the world and so in the low income parts of high income countries there's often that problem that that's what people are able to afford and so they're going to be filling up with that type of food and tending to be able to get overweight or obese even if they're quite empowered. Thanks so much for clarifying that as the chronic undernutrition is not the only risk factor for tight-fired diabetes. What are the other risk factors that can lead to a person developing tight-fired diabetes? I ask both of you this question if we could start with your professor anyhow. If you think in terms of an individual who may be born in a family which is not low-sufficient or a shaknot, you might think that during pregnancy the mother may have had another illness. For example, even in a well developed society in terms of socioeconomic status, you may very well have a mother who has hypertension and pregnancy and the blood circulation through the pleasant term may be poor and that could lead to a low-birth weight fetus, an infant who's born low-birth weight and subsequently there may be failure to thrive due to other features which may be there in this individual as well. So sporadically it's possible that these individuals may be exposed to some form of problem during pregnancy and then subsequently the child may have something syndromic or non-syndromic which may also lead to this condition. It is quite possible that in developed countries or even in developing countries and cities which have good neonatal intensive care units that we are increasingly seeing babies who are born very low births with even as low as 1.2 kilograms or even less than that. And many of these children are subsequently living. If they were to have diabetes at an early point of time, it very well might be a problem which is not endemic underneutrition, but something else which might be presentating these factors. Thank you. And Dr. Hawkins, would you like to add to that? Yes, thank you. I'd like to add that while global underneutrition, as we noted, is very important in the ideology of type 5, I can't overemphasize the role of individual nutrients in leading to this condition. So, one, for example, would be protein. We believe this to be so important both for the development of the beta cell as well as for normal functioning of the beta cell to secrete insulin. And then various micronutrients are believed to be very important for beta cell function. And one that comes immediately to mind is zinc. There's a number of other vitamins that are believed to be very important in normal beta cell function. And so a well-balanced diet that would contain a normal composition of micronutrients is incredibly important. And in certain settings, for example, where a diet might consist mainly of polished white rice, you can quickly see the imbalance. You can quickly see the lack of protein and the lack of so many of these vital micronutrients. And we believe that all of that is very important in the pathogenesis of type 5 diabetes. We talked about the origins and the importance of early diagnosis. But for the many young adults already living with this condition, the question becomes, what are potential treatments for these young adults who are living with type 5 diabetes? So, the most important answer that I have to emphasize is we don't yet know. And this is why it's so important to embark now upon this enormous effort, enormous global approach to this condition. Because the problem is that at the present time, individuals with this condition often present late after they've had it for a while, they present the rural clinics, they are started on whatever medications might be available there. And when we've been studying them, when we've been able to find these individuals to study them in comprehensive studies, we notice, as consistent with literature, that their glucose levels tend to be very high. And what that means is that it makes it very difficult to say that anything that they've been currently on is ideal for their treatment. We just simply don't know. What we can say is that because they have marked defects in insulin secretion, they may need small amounts of insulin. That's something we're going to have to very carefully study. But I'd like to put the emphasis on the word small as they require insulin. It's likely to be small amount because as you've heard, as both say, these individuals are sensitive to insulin, very sensitive. So a small amount would go a long way. And then of course, they may also require oral medications that would increase insulin secretion. The key thing though is safety here. Because unfortunately, treating with insulin or sulfolory is, that's that homily used drug all around the world that's cheap for insulin, increasing insulin secretion. These drugs, both insulin and sulfolory is, can result in many deaths from low blood sugar. And I've encountered this personally with many young people in Ubonne. They're in the hospital. Their blood sugar levels are high. They're started on insulin or sulfolory is as though they had either type one or type two. So at the doses that will be appropriate for those conditions. And then they're sent back to their villages where they encounter at times extreme food insecurity. So we so many times had the story that they were thriving when they got back to their village. Then one morning, they just didn't wake up and the presumed cause of death was low blood sugar. Now the other issue we thought is that there's been so many great drugs developed for type two diabetes, but in so many cases, they had never been studied in lean individuals. Or we know that they shouldn't be given to lean individuals because they cause weight loss, which would be detrimental. Of course, that weight loss is not just fat, which these people don't have, but it would also involve losing muscle and other vital tissues to be very detrimental. And so we want to avoid medications that would make them lose weight. We do have many questions and this is why the research is so urgently needed. We can ask some theoretical questions. For example, SGLT2 inhibitors, which make people put out more glucose in their urine, might be terrific because in people with very high blood glucose levels, they could dramatically reduce those glucose levels. However, given that type five diabetes is associated with quite low insulin levels, there's a serious concern that this might have these individuals over into ketoacidosis, which is already a concern with these drugs. And other loss of drugs that could be terrific would be DPP-4 inhibitors that can increase insulin secretion without causing hypoglycemia. So they should be very safe in these people. They may not be powerful enough to completely correct the hypoglycemia, but they might be very useful in combination. So I hope all of this shows you why more research is urgently needed. It definitely does. Thank you so much. I have to say that most of the podcasts, I have questions at the top of my mind and I get an opportunity to answer them. But the both of you are just knocking out the questions that I have lingering because I did want to come back to that earlier in our talk. You said that a lot of these individuals come to you with high glucose and they were surviving without insulin. So I was wondering, like, how was that possible? And I did a fantastic job for answering that and the conundrum of which medications will work for them. So I mentioned in the opening at the recent IDF World Diabetes Congress 2025 in Bangkok, Thailand, our IDF president, Professor Peter Schwartz announced the launch of a Type 5 Diabetes Working Group. Can you each share what prompted this initiative and why it's significant? So to say it's profoundly important because how much of what we mentioned revolves around the fact that this form of diabetes does not occur in the main diabetes textbooks that are used around the world. And so it's vitally important that just as we've recognized and thank you for so many things you've said about how calm in this condition is around the world, about how little we get to know about it. So it's vitally important that this be studied in a formal way, that this be studied in a global way. It's important that we can gather experts from all around the world. We know that it's a problem of insulin secretions. So we must have much expertise coming from around the world to guide us in that, to guide us in how to diagnose it, to guide us in how to treat it, how to even set up these types of studies. We very much need epidemiology. We need to examine where this condition is prevalent around the world and how it might differ in various geographical regions. And so underline all of this, the need for careful, high-collibal research. Thankfully, we've already established collaborations. We've already been in conversation with over 100 people. We're now investigating around the world in different areas. This is still fluid. We're still gathering people who are doing an interest in helping us in these enterprises. And then I'd love for Professor Nehal to speak more about how, in fact, that we are moving forward in different parts of the world to be able to get regional leaders involved and move this research forward. So it's also, I'd like to end my remarks by saying it's also very significant because this is a type of diabetes that occurs in lower middle and country countries. We know that now that over 80% of new cases of diabetes are occurring in those parts of the world. So to have the launch of a working group for a type of diabetes that's unique to lower middle and country countries and a working group that will represent all parts of the world is highly significant. Thank you, Philis. Thank you, Meredith, for that lovely introduction to this very important aspect of a working group. Now when we talk about a working group, we are addressing several areas. We're talking about the epidemiological aspect. How sure are we that do we know that it's actually 20 to 25 million across the world who are involved? Quite possibly yes. Quite possibly more. We have traditionally thought about it as a diabetes which occurs in young individuals. Although less than 30 years of age, but remember that in many epidemiological studies of the past looking back at the ones in Bangladesh, etc. That people have actually presented in their 30s or 40s. In clinics, very often the physicians have this spot in terms of making diagnosis of type to diabetes being the the common is form of disease. And as a result, almost every patient gets labeled as type 2 diabetes. But there could be a number of patients, not just needles and haystacks, much more than that, that you could actually be seeing patients with this condition. So epidemiology has to be studied across the world, across companies. We need to understand the pathogenesis to also much better. From the aspect of the functioning beta sir, we need to get down to see, this is an aspect an organ which cannot be biopsy. The pancreas is not an organ which can be touched by biopsy without causing serious problems to anybody. And that's what makes it so difficult. So therefore, kicking out cells, using stem cells, trying to make them grow and trying to see how they function and as to whether they produce insulin, whether the same stimulatory factors are responsible. This protein have an effect in improving the condition. So in vitro studies make a difference in terms of adding amino acids to make beta cells function better. So these are pathogenesis related questions which also need to be answered in this situation. So both epidemiological translation as well as very basic science questions about this condition needs to be. Are there other environmental factors which influence it? Are there parasites? Are there pollution? Are there other factors which may be also influencing these? We don't know the answer to these questions and therefore this would throw open a wide new arena. And finally, I'd like to say to fact, this gives us an opportunity for us to understand diabetes as a whole much better. We've talked about type 2 diabetes and there are people who also talk about diabetes as phenotypes which range from obese to normal weight to lean. It should be looking at the entire classification of diabetes from a different perspective. This type 5, throw in a totally new perspective as far as the classification of diabetes as a whole. This gives us points to ponder and important aspects for research in the future. Thank you, Boak, for giving us that thorough information about the working group. One of the goals of the working group is to develop formal diagnostic criteria and therapeutic guidelines for type 5 diabetes. Why are these formal definitions so important for clinicians and patients alike? Can you answer that for me, Dr. Hawkins? So this is profoundly important because type 5 diabetes differs so much from types 1 and 2 and as noted, those are the only types of diabetes currently described in textbook. Because I have often encountered when I give lectures in different places, different low and middle and conventures, at the end I'll hear over and over again. Why is it that when we are seeing so much of this condition, this is the first time we've actually heard anyone telling us about it? And so this is as absolutely vitally important that we define these carefully to be able to provide clear diagnostic criteria for people encountering this condition so that they will be able to know what it is that they're treating and then ultimately to be able to give them clear therapeutic guidelines so that we will not run into the situations that I described where inappropriately treating people as type 1 can cause death to hypoglycemia and inappropriately treating them with medications for type 2 can cause detrimental weight loss. So this is the key thing as you've heard today. Not only is type 5 diabetes unique, but there are also other forms of diabetes as you've heard that are unique to low and middle and conventures such as phyprocalus pancreas at diabetes. And so knowing specifically what type 5 is and is not and then ultimately knowing how to treat it could not only save a lot of lives from inappropriate treatments, but we know well that it's difficult and challenging to treat this condition. They're very prone to complications. They would have if not properly treated a very dire outlook, certain lives and tremendous morbidities. So being able to carefully and methodically study the treatment approaches and then to be able to outline clear therapeutic guidelines would be vitally important both to save lives as well as to dramatically change the outlook for these individuals around the world. The working group also plans to create a global research registry and education modules for healthcare professionals. What impact do you hope these efforts will have on diabetes care, especially in under-resourced settings? The impact of making a diagnosis of type 5 diabetes throws open several challenges. There are aspects of diagnostic abilities of various low income countries and of course as Meredith has very clearly mentioned that we are still not here as to what treatments are available or what treatments might work best in these patients. So this gives us an opportunity. Once we sensitize populations which we have been trying to do in various places, researchers and physicians in different parts of the world in countries which have this particular condition, we're trying to see as to whether we could improve diagnostic facilities in these areas. For example, CPAPTides are construed to be expensive but getting people to get these tests done in bulk in bigger numbers that actually cut down the cost. Similarly, the GAD antibody which is seldom done in many of these countries because it's once again construed to be expensive involves a simple test like an ELISA which can be done and if this expertise can be actually introduced in these countries, they would help in better diagnosis of other conditions as well as type 5 diabetes. So it throws open a whole new opportunity. When it comes to therapeutics, one of the easy ways of actually doing this is to explore existing databases of patients who have been treated for lean diabetes and looking at and seeing what treatments they have received. These are easy ways where one would be able to answer some of the questions as far as treatment of this particular condition is concerned. Throwing open more systems where people can be trained or taught as to how to diagnose and treat this condition would therefore throw in more new opportunities for physicians to handle the condition better. I'd like to ask a question. Just thinking about individuals with high glucose levels. As a person that did have a high glucose at diagnosis but again, I live with latent autoimmune diabetes and adults so it's all different. But I experience neuropathy and my hands and my feet. I also experience vision loss. Are these complications also ones that people would type 5 would experience? Yes, they would. Now, there's a couple of reasons. I had mentioned that these people are particularly prone to complications and I'd like to point a few things out. One is that because their blood sugar control tends to be very poor, that's tended to be quite a universal description of these individuals across the board. It may well be that it's the people caring for them because we haven't yet done the research because this is an entity that's so unknown that no one really knows how to treat them properly. They may also be in settings where there aren't as many resources for treating them. Be that as it may. They tend to have very high glucose levels. We know from big studies like the diabetes control and complications trial, we know that the higher the glucose levels, the more prone they are to exactly the types of complications you describe, the neuropathy, the vision loss, etc. Now I'd like to pause on neuropathy because intriguingly, that's one complication that seems to be even more proportionally described for this condition. And I would be intrigued to know, given that neuropathy can also be brought on by various micronutrient deficiencies and also pollutants and other situations that toxins that could be in the environment of these individuals. There's other researchers and deficits that they may have that make them particularly prone to neuropathy on top of the high glucose levels. All I could say is I have thoroughly enjoyed this conversation and I'm so sad that it is ending now. I think we'll need to have you back for a part two after the work in group has met a couple of times and you've made some choices and announcements that you'd like to share with us. A huge thank you to you both Dr. Hawkins and Dr. Thomas for helping us understand the complexity of type 5 diabetes, what it means for diagnosis and care and why this new diabetes classification could shape and improve personalized diabetes care. As we've learned, not every person with diabetes fits into type 1 or type 2 and by adopting a more detailed classification system. We can improve diagnosis treatment and outcomes for undying those people and people living with diabetes. Thank you so much for coming out today. And thank you to you. This has been a wonderful opportunity for us to have a chance to broadly share what is of such vital importance to us and we believe so many with this condition. Thank you. Thank you, Felicia. It's been a wonderful opportunity and we look forward to talking to you further. And thank you to our listeners for joining us to keep up to date on the outcomes of the IDF Type 5 Diabetes Work Group. Visit the IDF website IDF.org. We'll be back soon with another episode of Detalk. [BLANK_AUDIO]