Diabetes Part 1

Welcome back to MedPods, the podcast on medical topics from the Department of Internal Medicine at AFMC. Continuing with the series, today we have a very important topic being covered by Wing Commander Sandeep Kumar, Associate Professor in Medicine and Endocrinologist in the Department of Internal Medicine at AFMC. An alumnus of AFMC, Sandeep has a doctorate from National Board in Endocrinology. Today he shall be talking to us on a very relevant topic of Diabetes mellitus. It's a topic which is so vast that we will have to cover it in a series of podcast which we shall be starting from today. In this podcast, we shall be covering on certain basic aspects of this condition which assumed pandemic proportions in the last few decades and the particular zone in which our country comes, the genetic loading followed by the environmental effects has led to a large number of patients of diabetes being present in this subcontinent. In this topic, we shall also be covering the way one would diagnose diabetes, one would go about screening for diabetes because this condition often happens to be silent and also certain basic aspects of management before we close the discussion today. Welcome Sandeep. Thank you sir for giving me this opportunity and I must tell my audience today that I would be speaking today in front of a person who himself is a stalwart in endocrinology and diabetes. So sir, I am going to learn from today's interaction. Thank you Sandeep. So today I shall be posing your question and in the conversation that we are going to have over the next few minutes, we hope that the students will learn about this very important condition. I again urge all the students to make notes and also come back to us with any clarification or doubts that they have on this topic so that we can clarify them and also please continue to give us the feedback the way you've been giving. So starting on today's podcast, when we talk about diabetes we do understand that it's an extremely common condition, in fact almost half the patients who come to the hospital also have a coexisting diabetes which complicates their management as well as prognosis. So when you look at the population size, what is the problem scenario as far as diabetes in our country is concerned? So it is a big problem. So whatever data we have, it is said that about 537 million people in the world are living with the diabetes mellitus and out of this 537 million, one patient out of every six is contributed by India, that is the proportion of the problem as of now in the world. Coming to the Indian scenario, so it is said that about 74.9 billion people in India are living with the diabetes mellitus and it corresponds to prevalence rate of about 9.6 percent. And so when I break this into the fraction compared to the normal population, it is seen that one in every three households in India are having a diabetes mellitus and one in every 11 normal person is having a diabetes in India. And it is not only this cross-sectional information which is important but more worrying is that that most of these people are not diagnosed because diabetes does not cause any symptoms during the initial stages. And during the times to come it is said that in about six years down the line that is about in 2030, there will be about 125 million people with diabetes who will be diagnosed in India. So it is a big problem and the problem which is going to rise exponentially. That is actually very alarming and in fact over the last few decades that we have been in this speciality, we ourselves have noticed that the way the numbers have been rising around us. So it is very important for the students to understand this condition well. In fact, what we thought of tuberculosis in the past as a mark of literacy as far as knowledge is concerned in medicine, I think now if you do not know diabetes, I think as far as medicine is concerned you are illiterate. So that is the importance of diabetes and learning about it for students is concerned. So a condition like this which is often silent, it is very important that we look for it very seriously and diagnose it and also have an understanding of how to diagnose because as we understand in most cases once diagnosed, this diagnosis is permanent and that is the reason why we should be very clear how we are going to label a person to be having diabetes. So please tell us how would you diagnose the diabetes in a person? So there would be two scenarios when we face a patient or we would approach a patient towards a diagnosis of diabetes. So one scenario would be a patient presents with a classical symptoms of diabetes and these are hyperosmotic symptoms means the patient present with symptoms of polyuria, polydipsia, polyphagia and weight loss. So once these symptoms are present and we are able to have a random blood glucose which is more equal to or more than 200 milligram per deciliter, we can safely diagnose this patient with the diabetes malitis and the random means any time of the day without regard to time since previous me. So coming to the second scenario sir. So in this we have a suspicion of diabetes or we are screening a population for diabetes. In this we utilize the three values. We can utilize a fasting plasma glucose or a 2 hour post glucose load, glucose, plasma glucose value or we can also utilize HVA1c level. So fasting plasma glucose is more than 126 milligram per deciliter or 2 hour post glucose load glucose is more than 200 milligram per deciliter or HVA1c value equal to or more than 6.5% patient can be diagnosed at diabetes. I just want to emphasize here that any one of these four values are enough to diagnose the patient the diabetes malitis but whenever there is an ambiguity that we should do a we should check for the two tests at the same time. So in case of ambiguity two tests in the same time if positive patient can be diagnosed at diabetes or even at the different times a patient can be labelled as a diabetes malitis. Okay so this is something that the students must be very clear about because often patients are diagnosed wrongly based on criteria which people are not clear about and leads to lot of anxiety in patients and also falls diagnosis. So that is something that we must ensure that we are very clear about and also we must remember that fasting means at least 8 hours of not having had any calorie intake so that is very important. Now these cut-offs we have seen over decades how they have changed so what is the rationale behind these cut-offs and how are they decided by the various agencies which actually sort of create these criteria for diagnosis. So Boyle Health Organization and American Diabetes Association has worked extensively with regard to coming to the cut-off values for the diabetes malitis. So these cut-offs were derived after various population based studies were done and these specific cut-offs are based on the basically the related to the development of the specific diabetes related complication mainly the diabetic retinopathy. So they saw in this study group and which mainly comprised of Pima Indians, Hispanic, Egyptian populations. So they saw that beyond these cut-off these patients were developing the diabetes specific microvascular complication that is diabetic retinopathy. Okay and you also spoke about HBA1C which was something that has come fairly recently in the diagnostic criteria for diabetes till then we were only using fasting and post-glucosal glucose values. Now to make the audience understand what is HBA1C I just want you to elaborate slightly on what is HBA1C, how does it differ from usual fasting or post-meal glucose and what is its relevance as far as diagnosis is concerned. HBA1C is a cumulative exposure of RGCs to the blood glucose and it represents the long term glycemic control. So basically so when we do a fasting plasma glucose or post-2R glucose low glucose value they just give us a cross-sectional or real-time glucose value during that particular period. But to have an idea of the longer term control we need to have a certain tool which help us in diagnosing the longer term glycemic control. So with this need the HBA1C was discovered and it represent basically the glycation of the hemoglobin in the RBCs. So basically what happens is the glucose get irreversibly bound to the end terminal part of the valine in the beta chain of the hemoglobin and it would stay there for at least a lifetime life duration of the RBCs. So this gave us a cumulative glycemic control over the period of the lifespan of the RBC that is about 120 days and it has a very useful role in the clinical practice in the sense that it is easy to calculate there is no fasting which is required and it can be tested any time of the day but it has a certain shortcomings also. For obvious reason we can understand if there are any conditions in the people which can affect the RBC survival like pregnancy, various liver disease, kidney disease, blood transfusion, various hemoglobinopathies and even various changes in the iron and nutritional component of the blood they can affect the HBA1C value. So if there is an increased RBC turnover in the condition in the hemolysis hemoglobinopathies like sickle cell disease, recent transfusion, acute blood loss and chronic liver disease we can have a falsely low HBA1C value and on the other hand if there are conditions which decreases the red cell turnover means if the red cell survival increases then we can have a falsely high HBA1C value and there is few examples of such conditions are vitamin B12 deficiency, iron deficiency, alcoholism and hyperbillirubinemia and uremia. So it is a very useful tool to calculate the long term glycemic control however it is not free from shortcomings which I have mentioned. And another thing to note here is that the sensitivity of the HBA1C is also low compared to the fasting plasma glucose which is equivalent to 44%. So this had to be interpreted with the caution in the clinical scenario. So what we understand is that HBA1C gives us sort of a long duration glycemic control over a period of 3 months that is a lifespan of RBC. So unlike fasting and post-need glucose which are a point values for that particular day this would mean tell us how the glucose values have been over the past 3 months and since it is a protein bound glucose it is also telling us in a way that this is how glucose is being bound to other proteins like collagen which leads to complications. So that is why there is this correlation of HBA1C with other complications. However like we see fasting or pre-meaned glucose and we see post-meaned glucose over a day. So over a period of 3 months the blood glucose has been continuously fluctuating. So given a HBA1C value what is the contribution of fasting or pre-meaned glucose and post-meaned glucose as far as HBA1C is concerned. So this can be basically analyzed from the very beautiful hypothesis which was given by the bonyers and it is also called as bonyers hypothesis. So basically it dissects the contribution of the fasting and post-prandial hyperglycemia at different levels of HBA1C. So this hypothesis says when the glycemic control is good and which was defined by him as HBA1C less than 7.3% the 70% of the contribution glycemic burden comes from the post-prandial hyperglycemia. On the contrary when the blood glycemic control is not good means if HBA1C was more than 10.2% in this study then there was a 70% of contribution comes from the fasting hyperglycemia. So the message is that at the good HBA1C value the majority of the contribution will come from the post-prandial glucose value in uncontrolled HBA1C or at higher HBA1C the majority of the contribution will come from the fasting plasma glucose value and the clinical inference from this is that whenever we get uncontrolled glucose we should try to control the fasting first. So this is very important concept that has to be understood because irrespective of how well you control the post-meal values if the fasting and free meal are high the HBA1C is unlikely to come down and once you achieve the HBA1C around your target of around 7.5 if you have not controlled the post-meal glucose better you can never achieve the ideal target of less than 7. So it is very important and that is how various drugs have to be prescribed which we will talk about when we talk about the management of diabetes. Now like blood pressure sugar values are also a continuum so when we label a person diabetes based on the criteria there is a particular value below that criteria which also tends to cause some amount of damage to the tissues however not to the extent that hyperglycemia as per the criteria could cause. So like you have diabetes and you have normal glucose values you have a range which is called pre-diabetes where individual has does not have diabetes but is not normal as well. So would you like to elaborate on this what are the values and what are the criteria on which we label a person to be having pre-diabetes. This intermediate stage between the normal blood glucose value and the over-diabetes we call as the pre-diabetes and in fact for all the students this is the most important concept to understand because this is a window of a great opportunity where we can intervene and we can even you know prevent the occurrence of diabetes and we can even also reverse or cure the pre-diabetes or the diabetes in such individuals. So basically the pre-diabetes is defined whenever we have a fasting plasma glucose value between 100 to 125 or post-glucose values between 140 to 199 milligram per deciliter and HVA1C value between 5.7 percent to 6.4 percent. So when any of these three is present we can diagnose the patient as a pre-diabetes whenever there is an isolated impairment of the fasting we call this patient to have an impaired fasting glucose. When the patient is having isolated post-glucose load derangement that is between 140 to 199 we set this patient to have a pre-diabetes. So why this is very important to understand and diagnose this stage is that I have already said that this is a great opportunity where we can intervene and the main intervention lies is that the patient can follow the aggressive lifestyle modification and the lessons comes from the landmark diabetes prevention program where the prevention of the diabetes can be done if we reduce as much as 7 percent of the weight loss. That is one concept which we need to remember and the second concept which we need to remember with respect to pre-diabetes is that pre-diabetes similarly like over diabetes is also associated with the increased insulin resistance. So if there is an increase in insulin resistance the pre-diabetes patient are not immune from various microvascular or macrovascular complications. In fact there are studies which are available which have proved that pre-diabetes patient may have a grease risk of atherosclerotic cardiovascular disease so it is very important to address this population to prevention of the atherosclerotic cardiovascular disease and even it has been seen from the landmark trials that pre-diabetes also have a microvascular complication and even neuropathy has been seen in these population. So it is very important that it is a chance given to us to sort of intervene and prevent people and from going into the stage of diabetes because that is where the complication risk could suddenly rise beyond what is seen with pre-diabetes. And also the fact that since most of the patients are likely to be asymptomatic at this stage the importance of screening would come into picture. So my next question is about screening and as we understand screening for any condition especially involves conditions where individuals remain asymptomatic and where early diagnosis is important because it can be prevented or complications can be prevented and there are treatments available for that. So when it comes to diabetes who are the people who you recommend that should be screened and how do we screen them? Screening in diabetes mellitus is one of the most important intervention and possibly it is not properly being obeyed in all the countries and that includes India as well. That is why when we were discussing about the privilege or burden of the diabetes mellitus we said that most of the patients are go undiagnosed with pre-diabetes and diabetes. So when we follow the American Diabetes Association guidance, every individual who is more than 35 years of age and I again want to re-emphasize that more than 35 years of age should undergo screening for the diabetes that is the one thing which every student should remember. Coming to the second criteria for the screening is any individual in India or who has a body mass index more than 23 kilogram per meter square and has a one additional risk factor which I would be telling they should be screened for the diabetes and what are these additional risk factors? That is first degree related with the diabetes, high risk rates and ethnicity of which the Indians are part of and others are like African American, Latin American, Native Americans and Pacific Islanders, history of cardiovascular disease, presence of hypertension which is defined as blood pressure more than 130 by 80 millimetre of mercury or on the therapy for hypertension, HDL cholesterol less than 35 milligram per deciliter, triglyceride value more than 250 milligram per deciliter, presence of polycystic ovarian syndrome, physical inactivity or other conditions which are associated with insulin resistance like presence of acanthus nitric acid or severe obesity. So if any of these one is present and the body mass index is more than 23 kilogram per meter square these individuals should be screened for the diabetes and other criteria for screening are all the ladies who had a gestational diabetes should be lifelong screened for the diabetes malitis every three years. All the individual who had a pre-diabetes which we were discussing in the earlier part of this discussion they should be screened for the diabetes every year, yearly. Another the people who are with HIV people who are taking drugs which can cause diabetes or hyperglycemia like corticosteroids or patients who have history of pancreatitis should be screened for diabetes. For all the people for the for the all other people who are left not included in this criteria the I've already mentioned the age more than 35 to constitute the screening criteria for the diabetes malitis. So out of this all the comprehensive discussion we can well imagine that if we try to fit in this screening criteria in a day to day practice in fact most of the patients would fit into or satisfy the requirement of the screening criteria for the diabetes malitis and at present probably this is not happening in a day to day practice. So I think what we must understand is that one big step that we can take in preventing this epidemics from increasing further is to screen very aggressively and manage them with lifestyle modification. Now once we have diagnosed diabetes we understand that most of the time these patients are very different from each other and diabetes is not a very homogenous disease it has various other factors to be considered so the diagnosis of diabetes may be common but then the types of diabetes are so many that one needs to be very sure which type of diabetes a patient has because the management and prognosis would differ. So can you elaborate on the classification of diabetes and very simplistically explain to the students that by looking at a patient how can they predict what kind of diabetes this patient would be having. So American Diabetes Association and I'm talking about the latest guidance which has come in 2024 so it has a very beautifully simplified the classification into the 4 broad groups. So group 1 includes the type 1 diabetes or also the diabetes which occurred due to the autoimmune destruction of the beta cell so that also includes the latent autoimmune diabetes of adulthood and that is also known by the short form of LADA. The second broad group includes the type 2 diabetes so what is a type 2 diabetes? Type 2 diabetes is a non-automated progressive loss of beta cell insulin secretion and in the background of the insulin resistance and metabolic syndrome so we can well imagine how those gotten right to the patient with the obesity and insulin resistance. Third group includes the all other specific type of the diabetes malitis which include monogenic diabetes syndromes like neonatal diabetes, majority onset diabetes of young which is also known as MODI, diseases of exocrine pancreas means whenever the patient has a pancreatitis, chronic pancreatitis which lead to the beta cell failure and patient develop diabetes malitis, certain drugs and chemicals which can cause diabetes, diabetes associated in HIV positive patient and after organ transplantation like which is also called as a post transplant diabetes malitis, these are included in the group 3. So group 4 is exclusive which has been kept for the gestational diabetes at this juncture it is also important to differentiate what is the gestational diabetes. So basically gestational diabetes is the new onset diabetes which happens at second and third trimester without any clinical evidence of overt diabetes during the pre gestational period. So if the patient has a pre gestational diabetes means the patient if there is any evidence which shows us that patient had diabetes before the pregnancy these patient would not be included in this fourth category. So this is the fourth broad group in which we classify the diabetes malitis according to ADA. However, over the period of time there are certain special mentions also and this is just for academic interest of knowing only but we should be student should be remembering we also have a like type 1.5 diabetes which is a name given to the later onset diabetes or to mean diabetes of adults that is LADA. So what is LADA? So LADA is nothing but a phenotypically a type 1 diabetic patient means this patient would not have a family history or this patient would not be obese this patient would not have a auto this this patient would not have a markers of the insulin resistance. However, this patient would have a positive antibody like a type 1 diabetes but this patient for initial few months that for generally it has been seen for first six months these patients do not require insulin and they are well controlled with the oral antidiaptic drugs but over the period of time they will go on to require even insulin like a type 1 diabetes. So basically this LADA is also called as a smoldering or slowly progressive type 1 diabetes malitis that is why ADA has grouped this into the type 1 group only that is the first group of the classification criteria. This is another there is another special mention of type 3c diabetes which is called utilized at times for the diabetes of exocrine pancreas. And now this is very very important like students would have seen that we are often perplexed when we see a patient who comes to diabetic specifically a young individual young male young female who comes and we are confused what to label him whether he is a type 1 diabetes or type 2 diabetes or a diabetes of exocrine pancreas or other monogenic diabetes. So let us discuss this. So I will give a very beautiful mnemonic that is a, a, b, b and cc. So a stands for age, so younger individual generally less than 35 would be a type 1 diabetic. Autoimmunity, next is for autoimmunity, presence of autoimmunity either we do the GAD 65 antibodies or we do the ilate cell antibodies or presence of other autoimmune disorders would suggest us a presence of the type 1 diabetes even the presence of the autoimmune polyglancocentrope in the patients. Body habitus, I am talking about the body mass index here, if there is a presence of obesity or overweight that would suggest us the type 2 diabetes, non-obese individual without any adiposity would suggest us a type 1 diabetes patient. Family history would be more common in the type 2 diabetes, family history would be less common in the type 1 diabetes and the patient who would require insulin initially means patients who are not controlled with the oral drugs would be a type 1 diabetes. In fact, this is basically a diffused way of explaining this in the type 1 diabetes patient generally develop a type T key 2 acidosis even if they are not given the insulin and in fact they first presented the type T key 2 acidosis only. On the other hand, there are certain things which would suggest us about the pancreatic origin diabetes for we would have a patient who would abuse alcohol, these patients may have certain features, clinical features to suggest the exoprime insufficiency means they would have a steatory, GI disturbances, bloating and the in the setting of the pain abdomen or in the background history of alcohol consumption or there would be some stigma or telltale signs or presence of the gallstone diseases in these patients. So basically, these are the scenarios or clinical clues which help us in homing towards the various types of the diabetes malitis. Now coming a word about the monogenic diabetes Modi which we discussed, so in the Modi what happens is these patients generally are non-opies, they don't have markers of the insulin resistance but they have a multiple generation history of the diabetes. So when we encounter a young individual who has early onset diabetes without obesity or markers of the insulin resistance and there is a presence of multiple generation, in fact we look for the three generation in a clinical practice, such patients should be suspected to have a Modi diabetes and in appropriate setting of a requisite genetic test should be done to diagnose them because the treatment strategies for them would be different subsequently. Okay, so that's a very elaborate description of the various types of diabetes and I'm sure the audience must be wondering how complex it is when it comes to diabetes, however it looks so simple. So I understand that students would be a bit perplexed, it's not as difficult because very beautifully the mnemonic that has been given of AABBCC is way of assessing a patient upfront but often everything is not so black and white and we end up diagnosing the actual type of diabetes only after a few years of follow-up in a patient. So we will actually talk about these conditions more in detail when we address the specific types of diabetes in our future podcast. So before we end today's podcast I would like Sandeep to tell us about as far as Indians are concerned what are the peculiar characteristics of diabetes, we have so many types of diabetes that we can encounter, but when we have a patient who is from this subcontinent what are the peculiarities that you notice as far as diabetes is concerned. So Indians have a very peculiar characteristics with respect to diabetes and sadly we have a dearth of enough literature and we more often take information from the western data. So what has been seen that in Indians the diabetes occurs at a younger age means a decade earlier compared to the western counterpart, diabetes in the Indian population occur at a lower body mass index and whenever there is a pre-diabetes the progression from the pre-diabetes to diabetes occur at a faster rate in the Indian population. Indians have more abdominal adipositis which is also representative of the visceral fat and we all know the increased accumulation of the visceral fat is associated with increased pro-inflammatory factors which will increase insulin resistance and at the molecular level it has been seen that Indians are associated with a higher insulin resistance. In fact I would like the students to remember that the landmark or the classical the Yajnik and Yajnik paradox which has been given by the doctor Yajnik who is one of the renowned diabeticologist from India and in fact Pune itself and he demonstrated in his study that Indians with the same body mass index would be having a higher body fat percentage and this body fat would be more a chemically active to increase pro-inflammatory factors. And another thing which I want to highlight here is almost half of the population in India is unaware about their disease means for every one diabetic who is diagnosed in India there is one remain who to be undiagnosed. And I also bring I also want to discuss here about the concept of the thrifty genotype hypothesis which students to remember so what happens is during the earlier development stages whenever there was a scarcity of the food and which was the truth in the India about half a decade or 60-70 years back. So during those stages what happened that people who had a scarce food the body automatically selected the genes which were associated with the decreased insulin secretion and the diseases which genes which are associated with the increased insulin resistance so that these patients have a proper utilization of their metabolic fuel. Now with the advancement of the economy there is increased availability of the food and the patient have obesity and insulin resistance. So still these thrifty genotype genotype because of this thrifty genotype hypothesis these genes are still active and there is a decreased insulin secretion and increased insulin resistance and this also hypothesis is also our explanation of increased occurrence of the insulin resistance and diabetes in Indian population. Yeah that's a very interesting way of actually hypothesizing why there is such a large number of patients of diabetes being diagnosed especially in this subcontinent. Thank you Sandeep. I think this podcast has been extremely comprehensive for a topic which is very complex needs some effort to understand but all said and done this is one topic that every student needs to know because without this managing patients in any specialty that they choose in future is likely to be difficult. So we end this podcast at this time what I would request these students is to come back to us with any doubts or clarification that they need and also their feedback. In future we shall talk about diabetes of various specific types we will go into the management aspects and also the complications of diabetes and their management which can be both acute and chronic complications. So thank you very much Sandeep. Thank you sir.