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Unified Theory for the Pathogenesis of Diabetes

Oct 12 | 3:00 PM

Gone are the days when patients were classified as type 1, type 2 diabetes and others. With Increasing understanding of the pathogenesis of diabetes mellitus, diabetes is now understood to be a 'spectrum that unifies the disease rather than "buckets" which divides it. In this didactic talk we are going to discuss the unifying theory for understanding the pathogenesis of diabetes, newer classification and subclassifications of diabetes based on the clinical clues that tell us about the underlying pathophysiology. For those who are dealing with patients with diabetes mellitus on day to day basis this lecture will prove to be very useful for better management of patients.

0:00 [Music] 0:10 good evening everyone and we're so glad you could be here this evening i'm dr mavedha and on behalf of team netflix i 0:17 welcome you all to today's session today we have with us uh dr omlakhani he 0:23 is a consultant endocrinologist working at zaider's hospital amdabad and he's also considered as one of the top 0:30 young endocrinologists by the endocrinology community of india and serve expertise 0:37 include endocrine endocrine oncology metabolic bone disease 0:42 pediatric endocrinology and the use of new technology in the management of diabetes like this thank you so much and 0:50 over to you sir i will stop my presentation and start your thinking stuff 0:55 sure yeah thank you so much so uh you know 1:01 today i think it's a great opportunity for me to speak on this a very interesting forum 1:06 and you know i was told to choose the topic of my choice and rarely do you get an opportunity to speak on something 1:13 which you really enjoy speaking on so this is going to be you know you give it you know i almost give a talk every 1:20 you know all the other day but this is something which is going to come from my heart and 1:26 you'll learn a lot of things i have learned over a period of years so it's going to be very very interesting 1:32 so what i'm going to talk about is unifying theory for the pathogenesis of diabetes mellitus 1:38 and more importantly its practical applications in day-to-day clinical practice 1:44 now why unifying theory we all heard about unifying theory field 1:50 theory in physics this is like what einstein and all the great 1:57 physicists of their time tried to combine you know they tried to say that 2:03 what are the unifying forces is there a formula by which you can explain all the forces of the universe 2:10 unfortunately einstein in his lifetime nor were the other physicists in their lifetime able to achieve this 2:18 but the thing is that with diabetes mellitus we have an understanding we have an 2:25 understanding of the pathogenesis with which we can unify the various forms of diabetes and try and understand it from 2:32 one single context now the first thing you have to understand 2:37 and first thing you have to learn is to unlearn sometimes over a period of time we learn 2:42 certain things which may not be the right thing to learn so sometimes we need to take a step back 2:49 and unlearn a lot of things and today in this next well 30 minutes or so 2:56 i want you to forget the buckets of type 1 type 2 diabetes 3:01 we are going to move away from buckets and move towards what i would like to call a spectrum 3:08 so diabetes mellitus in all its forms in my opinion is a spectrum 3:14 of the disease rather than single buckets where which you put the patient into 3:19 so we often tend to label a patient as type one we tend to label a patient as type two we tend to label a patient as 3:26 pancreatic diabetes but what we forget is that these are all parts of one spectrum rather than 3:34 having one just just a single bucket and very interestingly sometimes patients can move across the spectrum which is 3:41 the very interesting part so if in one line you ask b 3:47 what is the unifying theory for pathogenesis of diabetes mellitus it's very very very simple 3:54 it's diabetes mellitus is an imbalance between insulin resistance 4:00 and insulin production that is beta cell function to understand this is very simple 4:08 now we all know why this is very true it's because this holds true for every 4:14 other endocrine disease that we see every other endocrine disease that we see in clinical practice is an imbalance 4:21 between the hormone production and the hormone action and that is what ultimately really 4:28 defines any endocrine disease and diabetes mellitus is an endocrine disease at the end of the day 4:34 so whatever holds true for a hypothyroidism or for a parathyroid or for a testosterone also holds true for 4:42 diabetes mellitus only thing is the resistance part is relatively rare in other endocrine forms 4:49 whereas it is center stage to diabetes meniscus 4:54 now get this perspective the body tries to maintain a very steady 5:00 state of glucose control again fundamental to understanding endocrinology is to understand the fact 5:08 that body always tries to maintain homeostasis homeostasis means steady's physiological 5:14 state your temperature remains constant your blood pressure tends to remain constant 5:20 your pulse rate tends to remain constant within a narrow band same way your glucose 5:27 blood sugar also tends to remain constant within a narrow branch 5:32 now if you don't believe me try putting a continuous glucose monitor in yourself now assuming that you are 5:38 not suffering from diabetes mellitus or even pre-diabetic if you put continuous glucose monitor 5:44 cgm you'll find that almost all your sugars are within one narrow range 5:50 and believe me because i've done this several times on myself and i'm thankfully not suffering from diabetes 5:56 and i don't intend to as well so the point is that the body tries to maintain the glucose in a very narrow 6:04 spectrum right in a very narrow range and this range is where 6:10 body will try all its efforts to maintain that and that is what is known as eu glycemia 6:15 now there could be two situations for maintaining eu glycemia you need a 6:21 set of hormones the most important the center stage of all these hormones is insulin of course you have other players in the 6:27 field so you have the glucagon you have epinephrine you have the other hormones cortisol 6:32 peroxin all these hormones play a minor role but the major role the major the main actor of a play is insulin 6:41 and if the body is not able to produce insulin inadequate quantity 6:46 that is beta cell dysfunction then again you have hyperglycemia and the body is able to form insulin but 6:54 the insulin is not able to act as well as it should be that is what is known as insulin resistance 7:00 again you have hypoglycemia so all the forms of diabetes that we are 7:05 going to discuss now in the next slides we are going to take all our buckets all these type 1 7:12 and type 2 and everything and try to fit into our theory and we'll see how it really works perfectly magically 7:18 so all forms of diabetes at some level is an imbalance between insulin 7:23 resistance whereas versus a beta cell dysfunction let's move ahead so like i said 7:30 the body tries to maintain a state of eu glycemia at this stage you have insulin 7:35 resistance is equal to beta cell function okay so if you put it in a mathematical formula 7:41 insulin production is equal to insulin resistance and if this state is achieved you maintain a 7:47 perfectly normal blood glucose that is eukalysen now what happens when you have 7:53 hyperglycemia so any form of hyperglycemia you will have 7:59 the insulin resistance more than beta cell function now when i say insulin resistance is 8:05 more than beta cell functioning i don't always mean that the insulin resistance is high the insulin resistance may be normal 8:12 and the beta cell function may be less or the insulin resistance is high and the beta cell function may be normal 8:19 get my point right so to say you know if one one let's say one pen 8:25 i say is short i always say this pen is short in comparison to my other pen which is taught 8:32 right doesn't mean that this is the shortest pen in the world and doesn't mean that this is the tallest pen in the world what it means is that my black pen 8:39 is shorter than my red pen but perhaps my blue pen is taller than my red pink 8:45 right so what i'm trying to tell you is that in any situation either the insulin 8:51 resistance is high and the beta cell function is normal or the beta cell function is reduced and 8:57 insulin resistance is normal or it could be both insulin resistance is high beta cell function is low 9:04 so that's the basis of hyperglycemia or increased blood sugar 9:10 now conventionally we classify diabetes into three major forms type 1 diabetes type 2 diabetes and 9:17 other forms of diabetes now this is the traditional bucket like 9:22 i said we'll take this bucket and put it into a spectrum and i'll try to first 9:28 make you unlearn or try to see the conventional diabetes classification 9:34 from our fundamentals and then we'll try to reclassify that in a more different way 9:41 okay the other forms of diabetes are pancreatic diabetes just to name a few there are many gestational diabetes steroid induced 9:47 hypoglycemia now ovid-induced hyperglycemia hypodystrophies ladas modi's 9:53 everything right okay so now let's first talk about type one diabetes 9:59 now just to tell you uh this slide you might not be able to see it completely so all you can do is pinch 10:05 to zoom so you can pinch to zoom and you can see the slide much more clearly 10:10 so what happens in type 1 diabetes now type 1 diabetes is the classical classical 10:15 form of type 1 diabetes is a classical example of beta cell dysfunction 10:22 it's in fact not the most classical form in fact the most classical form of beta cell dysfunction would be when i 10:27 completely remove the pancreas there is no beta cell no pancreas no beta cell no insulin 10:34 but close to that you have another form which is beta cell dysfunction which happens with 10:40 type 1 diabetes now what happens in type 1 diabetes is that you have autoimmune damage to the beta cell so by 10:47 some mechanism you have damage to the beta cell and this damage to the beta cell prevents the beta cell from 10:53 releasing insulin right so this is the classical form of a 10:58 type 1 diabetes but what happens to insulin resistance in most cases the insulin resistance is 11:05 normal so in this is the situation where insulin resistance is more than beta 11:10 cell dysfunction beta cell insulin production but insulin resistance is more or less normal and the beta cell function is low 11:18 but let me tell you that even in type 1 diabetes the insulin resistance is often not normal 11:25 insulin resistance is in fact slightly higher if you're seeing a patient with type 1 11:30 diabetes in your practice or if you if you see these patients often always ask them how are you diagnosed to 11:36 have diabetes for the first time and they'll often tell you that the first time i develop fever i had you 11:42 know i had respiratory problem i developed covad something like that there is always a history of a trigger 11:48 and this trigger produces infection or inflammation remember always remember this point this 11:54 is an important pull remember to remember is that insulin resistance 11:59 when you have infection or inflammation infection or inflammation often leads to insulin resistance this is very very 12:05 very important this is a key fundamental this is what happens we see a lot of i practice in a 12:12 hospital setup so i see a lot of patients who have infections who have respiratory tract infections who tend to 12:18 have diabetic foot infection or urinary tract infection all these cases whenever they have infection their blood sugar 12:24 goes up so even at home their blood sugars are normal but when they get admitted the blood sugars go up why do they go up because infection produces a 12:31 sense of insulin resistance so sometimes what happens is a patient is 12:36 having an autoimmune damage to the beta cell but still there is homeostasis being maintained 12:42 but as soon as they develop infection the insulin resistance goes up and the beta cell is not able to catch up to 12:48 this insulin resistance and these patients go on to develop type 1 diabetes so even in type 1 diabetes initially at 12:53 the form of at the time of diagnosis they tend to have a sense of they have a tendency to insulin resistance 13:00 now sometimes you would have also heard about this phenomena called honeymoon phase so after some time with good glycemic 13:07 control a patient with type 1 diabetes often goes off insulin insulin is often stopped in some of this patient 13:13 for a brief period of time and this is honeymoon period and after that brief period of time the patient goes back to requiring insulin 13:20 so this is a brief honeymoon period now this happens a lot of patients with type 1 diabetes what happens is that with you 13:27 corrected the infection you're broken down there is a tendency to what is known as glucotoxicity or glucose 13:32 toxicity this glucotoxicity breaks down insulin resistance comes down the beta cell recovers slightly 13:39 right but this is enough to overcome the insulin resistance and the patient maintains a mutaglycemic state for a 13:45 brief period of time but as the disease progresses the beta cell function keeps declining 13:50 the patient goes on to develop a full-blown type 1 diabetes once again 13:55 so this is how a type 1 diabetes fits into our picture if you see this slide 14:02 right this is the a very beautiful cartoon showing on the left side you can see a normal uh beta cell 14:09 mass a normal isolate eyelet of pancreas and you can see the green portions in 14:14 this eyelid are the beta cells you can you can see what happens in type 1 diabetes so beta cells you can see the 14:21 green cells are less so when it when these patients are diagnosed with the first time they continue to have some 14:26 amount of beta cell function you can see but it is substantially reduced as you can see from the picture on the left but 14:32 as you go ahead in the if you go towards the right you can see that almost no beta cells are seen 14:38 and this is what happens in an advanced form of ripened patient so you can only see alpha cells which are blue in color 14:44 you don't see the beta cells same way you can see the picture below where like i said there is a triggering 14:50 event often an infection or inflammation which triggers this entire process the patient goes into a stage one then stage 14:56 two and then stage 3 which is the symptomatic form of type 1 diabetes so this is what happens in a patient 15:03 with type 1 diabetes so even in a patient with type 1 diabetes even though it's a classical example of 15:09 a beta cell dysfunction even they tend to have a little bit of insulin resistance 15:14 great moving on let's move to the type 2 diabetes spectrum so this is the other end of the spectrum right 15:21 even now remember this is not the extreme example the extreme example of insulin resistance 15:27 are conditions like autoimmune insulin resistance syndrome or conditions like like which are which are called lipo 15:33 dystrophies we'll discuss that lipo dystrophies later in a few slides so let's first take a pre-diabetes 15:39 situation now a pre-diabetes situation is a situation where you have eu glycemia 15:45 right where you have again the blood sugars are normal patient is pre-diabetics patients blood sugar is 15:51 slightly increased but they're not increased to the level of diabetes so you can say to an extent you are maintaining status of glycemia now in 15:58 this situation the insulin resistance is actually high the patient has higher insulin 16:04 resistance but the beta cell also increases its capacity to produce more insulin to 16:10 match up for this insulin resistance so what happens in these patients you have increased insulin resistance but you 16:16 have also increased beta cell function and again insulin resistance matches the beta cell function and the patient maintains euclision 16:23 this is a pre-diabetes situation right and in this situation you tend to have hepatic insulin resistance peripheral 16:30 insulin resistance because of obesity hepatic insulin resistance resistance because of fatty liver and then 16:35 clinically you will find patients having economists nigricans and so on so this is basically the pre-diabetes 16:43 situation where you tend to have a near eu glycemia but this near-eu 16:48 glycemia is maintained because you have insulin resistance high but the beta 16:54 cell is able to catch up with the insulin resistance now what happens when the disease 16:59 progresses so you have early type 2 diabetes in early type 2 diabetes now you develop 17:05 hyperglycemia now to understand early type 2 diabetes pathogenesis let me tell you about 17:10 animal models about atoms right so when they want to have animal models for type 2 diabetes what do they do they 17:18 remove certain parts of the hypothalamus in mice and this mice they 17:23 they remove the areas which tend to produce satiety now remember when you eat food after 17:29 some time when you eat food you tend to become you know your your body says that i had enough right i don't want to eat 17:35 more so you have satiety but this subtitle is what stops you from eating so if i 17:41 remove that part of the brain now if you are interested in this there is something known as hypothalamic obesity uh we had written a very interesting 17:47 paper on that you know you can search for it hypothylamic obesity we had a case report of that uh we also said that 17:53 you know right perhaps had hypothylamic obesity because you see the uh 17:58 what the stories of current wear they used to say that you know he had he did not have any society so keep eating so 18:04 this is what they do to this lab mice so they remove their satiety center and 18:09 they are given unlimited food so you give them it's a it's like party time for this uh mice right so to give them 18:16 remove their society center and you give them unlimited food so they keep eating they keep eating now they keep eating 18:21 they start becoming obese they start gaining weight now what happens that might start getting any weight by gaining weight 18:28 they start becoming in stretch up for this insulin resistance the beta cell keeps producing more and more and more 18:34 and more of insulin so at different stages of time 18:39 now all of these mice do not develop diabetes at different stages of time they keep eating they keep vitamins becoming more 18:46 obese and the insulin keeps being produced but at some point of time at different stages of time different mice 18:51 they start developing diabetes so at some point of time one mice's beta cell gives up thank i don't want to do this 18:57 anymore they stop producing more insulin the mice develop diabetes then there's another 19:03 mice whose beta cell gives up then the another mice level of sorry so this is what happens right so ultimately what 19:09 i'm trying to point out is that you know about rate limiting step in an enzymatic reaction right what is 19:15 the rate limiting step in diabetes in all forms of diabetes the rate limiting 19:20 step is beta cell function as long as your pancreas can produce more insulin to match the insulin 19:27 resistance you will not develop diabetes this is the fundamental process you have to understand 19:32 as soon as your insulin resists as soon as your beta cell gives up and it is not able to match up for the 19:39 insulin resistance the patient develops diabetes and this is exactly happens what happens in type 2 diabetes so in 19:44 type 2 diabetes insulin resistance is increased but the beta cell function is not able 19:49 to match up because of this and because of this they are they go into a situation called 19:54 early type types now there are certain forms of early effect to diabetes where the present is a flat bush diabetes rat 20:00 bush is a region in new york uh close to brooklyn uh where you know you had a lot 20:05 of uh poor african american american kids and at one point of time they observed a lot of these kids go on to 20:11 develop a similar form of ketosis form of diabetes and they come with diabetic ketoacidosis but you give them insulin 20:18 for some time after some time they go into remission so what happens in certain patients is 20:24 that there you know when you have people giving up so some sometimes you know you uh your boss calls you and you leave 20:30 your job next day i'm not going to this place right so that's sudden in some cases you plan your exit right 20:36 so you give your resignation then you're called by the hr then you give your you know notice period and 20:42 then you know gradually right so in lot of patients with type 2 diabetes you have you have the beta cell gradually 20:48 giving up so bts will give you a warning i'm going to give up i'm going to give up i'm going to give up eventually gives up and 20:53 you'll develop hyperglycemia but in certain cases the btsl just gives up suddenly right suddenly that 20:59 function is lost suddenly you have insulin resistance severely overwhelming the beta cell function in the patient is 21:04 so severe that patient even goes on to develop diabetic ketosis so this is what happens in early type of 21:11 diabetes and then you have this glucotoxic cycle which happens so with more blood sugar 21:16 you have more glucose in your ring more patient patients develop more polyuria polyphasia you have increased calorie 21:23 intake to compensate for that so you're losing glucose in urine you want to eat more more glucose means more sugar more 21:29 sugars means more beta cell dysfunction less insulin more hyperglycemia so this creates a vicious cycle of glucotoxicity 21:36 in this cycle then needs to be broken for a patient to really go back to 21:41 normal state what happens in a state of late so when the type 2 diabetes progresses 21:47 over a period of time the insulin resistance then reaches a state where it is static so insulin resistance reaches 21:53 a static point but the beta cell function continues to decline slowly over a process of time and that's why 21:58 you see a long remember type 2 diabetes is a lifelong disease in a lot of sense 22:03 of course you have patients who go into remission right lot of patients but at the same time if the beta cell is not preserved it continues to decline over a 22:10 period of time and then patient continues to at some point of time you know you you will have patients come and say that 22:16 i have uh you know i i could manage my diabetes uh with one 22:21 tablet but now i am not able to manage with you in three tablets right so it's a progressive decline of beta cell this 22:26 is what happens in a late direction moving ahead so this is again sequence 22:32 of events like i discussed again you know in terms of you see the islets of pancreas so you can see on the left you 22:37 can see robust islet but in early stage remember you can see you can see the green cell green color is increased slightly right uh and 22:45 later on as the insulin demand increases you can still see beta cells you can clearly see and you can see the beta cell have not declined too much right 22:51 but they'll gradually decline but what you see is this you know fibrillatory purple things you see these are amyloid deposits so as 22:59 peterson start declining more and more amyloid start getting deposited in place of beta cell and this this leads to 23:04 gradual and permanent decline of the beta cell over a period of time so early on you're able 23:10 to it's not permanent you can reverse it to a lot of extent but as the disease progresses it tends to create a 23:15 situation of permanence okay moving ahead so 23:20 as i talked to you about you know this is what i wanted to see show you that remember type 1 and type 2 diabetes are 23:27 extreme ends of spectrum but it's a spectrum it's not a bucket right so you can see here in this 23:33 very beautiful diagram you can see that what you're seeing is set of buckets so what you can see is uh you know you 23:41 from from top to bottom and bottom top so you see you know type 1 diabetes tends to occur at a 23:46 younger age type 2 more with age advanced you know if you see the obesity also the 23:52 pyramid is inverted so type 1 generally tends to occur uh in non-obese whereas you know uh with obesity you tend to 23:58 have more of type 2 metabolic syndrome hla dqb1 which is a marker for insulin 24:04 for autoimmunity in type 1 uh you have the other markers which are you know fto and other markers which are part of type 24:09 2 uh you have systemic inflammation you have auto antibodies your t cells c peptide 24:15 decline insulin requirement all of these but see what is important is that all of these are present in all 24:21 forms of that so whether it's a type 1 type 2 ladder you have though the frequency the tendency the amount is 24:29 less you can see type 1 even in elderly population you can have insulin requirement even in type 2 diabetes you 24:35 can have some c peptide decline in type 2 as well so there is 24:41 everything but the point is that it is at different levels in different forms so type 1 and type 2 are extreme forms 24:48 whereas the other forms of diabetes fall somewhere in the middle of this spectrum and in fact there are forms of diabetes 24:53 which are even more extreme than tripon and tech which will see in a few minutes okay now let's discuss so we understood 25:00 that how type 1 and type 2 really are so type 1 and type 2 are basically type 1 just 25:06 to summarize is a form where beta cell dysfunction predominates and type 2 diabetes is where you have the insulin 25:12 resistance predominant right but there is some amount of insulin resistance even in type 1 and there is definitely 25:18 beta cell dysfunction even in time so like i said it ultimately falls down to the fact that it's a spectrum 25:24 now other forms of diabetes and with this you will understand this process even better 25:30 so let's talk about gestational diabetes right so gestational diabetes is a condition where you have the patient was 25:36 you glycemic the patient was having normal sugars before pregnancy but during pregnancy somewhere in the middle 25:42 of pregnancy somewhere at about 24 to 28 weeks the patient develops diabetes now why does that happen 25:48 this is classical to what we discussed in that early and late diabetes so what happens is the patient had euglycemia 25:55 before pregnancy but the beta cell had to some extent decline so you had 26:01 the beta cell which was not very robust so you had n you have little bit of insulin resistance so you had this 26:06 situation where both things were compensated each other so the patient had normal blood sugar but 26:12 what happened in pregnancy as a pregnancy advances the insulin resistance advances and with the 26:18 increase of insulin resistance at about 24 to 28 weeks of pregnancy the beta cell is not able to match up with the 26:26 insulin resistance which happens because of pregnancy and because of that the patient develops hypoglycemia 26:32 this is what happens in gestational diabetes meningitis and in if your beta cell function was very good you are like 26:39 those mice were you know you keeps eating and yet does not develop diabetes so if your beta cell function is very 26:45 good then even this insulin resistance which is increase in pregnancy the beta cell is able to match up and that's what 26:50 happens in most of the normal pregnancies but in certain women the beta cell is not able to measure these 26:56 betas and not be able to match up these women go on to develop gestational activities and as soon as the delivery 27:03 happens the blood sugars again become normal why does it become normal because now that insulin resistance is gone so 27:09 that insulin resistance reduces and with the sudden fall of insulin resistance the beta cell is now able to match up 27:15 with the insulin resistance and the patient goes to normal pressure but gestational diabetes is like a stress 27:21 test for diabetes and those women who develop gestational diabetes are almost five to 27:27 seven times more likely to develop type 2 diabetes in future because if their insulin resistance increases 27:32 because of some other factor may be another pregnancy maybe increase weight obesity maybe post menopausal status and 27:39 this women will go on to develop diabetes in future so that is gestational diabetes what about steroid induced hyperglycemia 27:45 another something something we see very commonly with uh you know clinical practice similar to gestation diabetes 27:51 so again as long as the patient was not on steroid the patient maintained euglycemia but when you give steroids 27:57 you increase the insulin resistance and this increase insulin resistance exposes the poor beta cell reserve 28:03 patient develops diabetes now the steroid is stopped the insulin resistance comes down the beta cell is 28:09 able to match up and the patient goes to normal blood sugar so this is what happens in steroid use hypoglycemia in some patients the insulin resistance 28:16 becomes permanent it becomes continuously high especially when the steroid is given for a long time and the patient continues to maintain diabetes 28:22 diabetics unless treated what happens in pancreatic diet so 28:27 pancreatic diabetes is also known as type 3c diabetes very interestingly in an advanced form 28:34 of pancreatic diabetes let's say somebody who has chronic pancreatitis for a long time beta cells are completely depleted or somebody has a 28:41 pancreatic cancer or somebody develops a has a pancreatic surgery somebody undergoes a ripple surgery something 28:46 like that you have obviously less beta cell and hence you have developed diabetes so right it's very simple to 28:51 understand less of pancreas functioning less beta cells less beta cells more likely but it 28:58 is not as simple even in pancreatic diabetes in early forms of pancreatic pancreatic diabetes remember in acute 29:04 pancreatitis also you have diabetes and this early acute diabetes early acute forms of diabetes you tend 29:10 to have increased insulin resistance so in some of these early pancreatic diabetes also sometimes when you give 29:17 this patient metformin the patient develops not patient goes on to maintain normal blood sugar 29:22 very interesting right so in early forms of pancreatic diabetes you tend to have insulin resistance but 29:28 as the pancreatic diabetes progresses you tend to develop more beta cell dysfunction and eventually the patient 29:34 goes on to require insulin right so even within pancreatic diabetes 29:39 you tend to have a spectrum moving ahead kovid induced hyperglycemia very classical we see lot we saw a lot 29:46 of these patients so you have insulin resistance what produces insulin resistance in kovid inflammation steroid use obesity 29:54 right remember obese patients with covet had higher mortality on the other hand what produces poor 30:00 beta cell function obit 19 virus itself had a tendency it had you know it would it had 30:06 uh h2 receptors which are present in the pancreatic beta cells with which the virus gained entry into the cells and 30:12 because of this entry into the beta cells because damage to the beta cell and you develop uh you know this cova 19 30:18 virus induced diabetes and remember a lot of the patients who develop diabetes after covering 19 had permanent diabetes 30:24 we have seen this very commonly we use a lot of these patients uh in clinical practice now and some of these patients are poor baseline beta cell reserve 30:30 which kind of added to the problem so this is how so covid19 hyperglycemia was actually a very classical form of 30:36 diabetes where you had both the spectrum being easily visible to you and this in a very severe form and in fact the idea 30:43 of this unifying theory actually is very classically shown in kobe 192 separation 30:48 moving ahead lipo dystrophy now this is a very rare condition but we do see that in clinical practice 30:54 in lipo dystrophy this is a condition where you have uh some form some reason why you have destruction of the 31:01 adipose sites adipocytes right and this produces a very severe insulin resistance it's a pure insulin 31:07 resistance syndrome right it's a condition where you have pure in fact you have mainly peripheral insulin 31:12 resistance and in this case again lot of these patients with lipodystrophies do not develop diabetes mellitus but some of 31:19 these patients with lipo dystrophy go on to develop diabetes where those different life the difference lies in their beta cell function so if they're 31:26 in lipodystrophy if their you know insulin resistance keeps increasing and the beta cell keeps matching up 31:31 through this insulin resistance you don't develop a problem but if their insulin resistance 31:36 is high and the beta cell is not able to catch up the patient goes on to develop diabetes and this type of diabetes is 31:42 actually very difficult to manage because even if you give insulin from outside it's not going to work right so it's a very complicated form of diabetes 31:48 your insulin you have to give it very high doses or you need to use other strategies nowadays of course sgl2 is a 31:54 good option because it's completely bypasses the insulin pathway what is lada 32:00 lada is actually in fact you know the best way to understand lada is that lada it's actually a type of diabetes ladder 32:07 is nothing but a form of type 1 diabetes but it's a slowly developing type 1 diabetes so what happens is in all 32:13 patients the beta cell destruction so there is an autoimmune see the characteristics of an autoimmune disease 32:19 is not predictable in some patients there would be i i believe there would be patients who will have cad antibody 32:25 in their body but will never develop type one there'll be some people some children who have gad antibody and they 32:30 develop diabetes very early on within one to two years of life whereas some people develop type 1 diabetes much 32:37 later in their life even though they may be carrying the dead antibody so when you develop a type 1 diabetes very 32:43 slowly over a long period of time generally by definition after the age of 30 that is what is known as lada or 32:48 latent autoimmune diabetes of adulthood so lada is actually basically a form of 32:54 type 1 diabetes you have you have beta cell dysfunction but again you have the 33:00 proponents of insulin resistance also in these patients and as the age advances what happens the 33:06 insulin resistance of the patient increases because the insulin resistance increases the beta cell is exposed so 33:11 sometimes you know you have even a definition of blood they say that patient should be could should be on 33:16 oral anti diabetes for six months before they require insulin and why this definition is required because see what 33:22 happens is in the first six months actually there we are treating the insulin resistance and then the beta cell dysfunction is not able to match up 33:29 and then you require it right so that is what happens in a patient with ladder okay what about modi we're not discuss 33:35 modi i think it's a this is an area where i'm very interested in and perhaps in future we might have a discussion discussion on 33:41 moodly in more great detail it's a cluster of disorder with different patterns most of the time you have beta 33:46 cell dysfunction again in different unique ways in these questions so we'll discuss that in a later class right 33:52 so this was the the conventional diabetes spectrum 33:58 which you understood so like i said diabetes think of it as a as a spectrum and not a bucket or not a not a 34:05 different you know water tight buckets no they are not 34:10 so you know the time has now come to really give you a new classification of diabetes now there are certain ideas 34:16 which have come so in fact three ideas will discuss those three ideas but in fact i personally am not satisfied except for 34:22 one of the three ideas i think as some merit the other ones still i would think is not 34:29 uh the best way of characterizing diabetes in fact i feel that you know we should try and remove the buckets we should try 34:35 seeing patients in a more therapeutic approach you know what type of therapy you will give to 34:40 this patient that should be the priority rather than trying to label a patient as a type 1 type 2 type 3 c whatever right so 34:48 however there were attempts made for new classification of diabetes new clusters new buckets again unfortunately and what 34:55 are these attempts and what what do these really such as so el quest data this is from scandinavia 35:01 from sweden they came up with novel subgroups of adult diabetes in six uh 35:07 five to six different clusters right so they came up with different clusters of type of types of diabetes so they give 35:13 five clusters the sixth one which then later somebody as an editorial added uh 35:18 so there are five classical clusters of diabetes which taking they said the first is severe autoimmune diabetes 35:24 second is severe insulin deficient diabetes third is severe insulin resistant diabetes for this mod mild 35:31 obesity related diabetes and fifth is mild age related diabetes now why i like this because yes they have 35:37 also made buckets but this buckets are not watertight they are not type 1 type 2 others know 35:43 they're still you have the tendency to shift between these buckets and go to different buckets depending on 35:49 the clinical circumstance but at the same time it's still a bucket right and based on our model they still fit into 35:56 all into our model much very beautifully right so what is severe autoimmune form of diabetes this is basically type 1 or 36:03 ladder where there is autoimmune destruction of beta cell so if you see insulin resistance versus because of 36:08 this function this calls it to the beta cell confidence function category and what i really like about this is that they classify type 1 and lada is the 36:16 same and this is what i also believe because type 1 and lada are actually the same disease it's only that the 36:21 intensity of the disease is different right so it's type one and lada which is severe autoimmune diabetes 36:28 second is severe insulin deficient diabetes and severe insulin deficient diabetes here you have autoimmune 36:34 biomarkers and negative but you tend to have beta cell dysfunction and typically your pancreatic diabetes 36:41 will be classified as severe insulin deficient hormonality especially when it is ah over a long period so this is 36:47 actually again induced spectrum if you see this is again insulin beta cell dysfunction which is 36:52 the main problem here but it is it is a situation where you tend to have autoimmune markers which are negative 37:00 moving ahead we have severe insulin resistant form of diabetes where here the insulin resistance is prominent beta 37:07 cell dysfunction is also prominent so both the things are there but the insulin resistance is the primary driver 37:12 of the disease process and these patients tend to have higher risk of diabetic nephropathy and this type of patients we see not uncommonly in india 37:21 right so you have high insulin resistance low beta cell dysfunction but insulin resistance drives the process 37:26 and this this happens in patients who have more visceral adiposity and these patients are also more likely to develop 37:32 diabetic complications then you have mild obesity related diabetes this is the condition where the 37:38 insulin resistance is just about the beta cell function so the beta cell is able to catch up to a lot of extent but 37:44 at some point it just stops right and insulin resistance also stops and if this patient keeps increasing 37:50 insulin resistance the patient goes into bucket four to bucket three but if the patient maintains at this level the 37:56 patient develops what is known as mild obesity related diabetes right and then you have the fifth 38:01 category which is mild age related diabetes where with advancing gauge you 38:07 have slightly increased insulin resistance in everybody and you have slightly reduced beta cell dysfunction 38:12 beta cell function in everybody so this is basically age-related issue where again the diabetes is generally mild 38:19 just giving one or two medicines oral medicines you are able to do it in fact a lot of the patient you can control with dietary 38:25 modifications itself so this is how scandinave this is the scandinavian or 38:31 the sweden classification for uh diabetes by eliquistal and if they look at their own cluster 38:38 from scandinavian countries they had you know in the various buckets so you had again majority of the patient falling into 38:45 mild age related diabetes that is a cluster five but the reason is that they have they have 38:50 you know longer lifespans there and you know tend to have a lot of patience and a lot of these patients are on socialized medicine healthcare they come 38:56 into attention in india of course you will not find this type of pattern in fact the cluster you'll find in india more commonly i'll just show you in a 39:02 few minutes we have a similar study from india also uh again you know you have a lot of cluster one patient so scandinavian 39:08 countries have a lot of type 1 patients you can see 14 percent of patient from this group actually where type one 39:13 whereas in india believe this is very just you know somebody who is a postgraduate student 39:19 planning for a dm entrance exam the first common most common cause of diabetes in india is type 2 diabetes 39:26 second most common cause of diabetes in india is pancreatic diabetes it is not type 1 diabetes type 1 diabetes is third most 39:32 common so type 1 diabetes in terms of prevalence is less common than pancreatic diabetes 39:38 also but in this case you can see type 1 is more common because in scandinavian countries you have and to have more type 39:44 1 diabetes now you have this indian cluster so dr b mohan at all actually came up 39:50 with this clusters uh mainly classified so he removed type 1 he just made sub classifications of type 39:56 2 diabetes and which are very similar to the scandinavian classification so he said you have severe insulin deficient 40:02 diabetes right so these are basically again insulin deficiency again beta cell dysfunction is a major problem right so 40:09 again and and some of these patients can have some amount of pancreatic involvement as well 40:14 then you have the insulin resistance obese diabetes which is very similar to cluster four of the 40:20 scandinavian countries then you have combined insulin resistance and deficient diabetes 40:26 which is similar to cluster three of the scandinavian countries and then you have mild age related diabetes which is exactly the same 40:32 as the uh fourth classification and the fifth uh cluster of this so very similar clusters 40:38 but again in his cluster also 35 percent of the patients who had mild age related diabetes but in practice you don't see 40:44 this very common because they don't come to clinical attention very commonly unless you do a epidemiological study 40:49 the first second and third are the ones you will come to your clinical practice so to give you a picture of this a 40:54 severe insulin deficient diabetes patient will be something like you know they'll come with uh you know severe beta cell dysfunction so 41:01 they'll come with uh you know polyurea polytypia weight loss uh 41:07 they will have you know the weight will be reduced such kind of clinical picture uh the insulin resistant obese patient 41:13 will be exactly the opposite the patient will be obese you know there'll be weight gain all these things will be there and then 41:18 you have combined insulin resistance and this where again this is something you see in clinical practice as endocrinologist i see this category very 41:24 common where you have both the things which are bad and the patient these are the groups who should develop a lot of severe complications 41:32 another so the third classification which which i feel is in my opinion the best way of classifying is what is known 41:37 as a beta classification so a is basically autoimmune marker and beta is 41:43 the beta cell function so autoimmune marker whether they are present or absent the autoimmune markers typically 41:49 are guide antibody you have ia2 antibody iaa antibodies so these are znt8 antibodies are various antibodies these 41:55 are all markers of autoimmune disease or autoimmune diabetes which is basically in definition type 1 diabetes so when 42:02 you have autoimmunity present and the beta cell is not functioning so your beta cell deficient this is classical 42:09 type 1 diabetes when you have autoimmunity present and beta cell function is still present to 42:14 some extent this is lada autoimmunity is negative but beta cell is negative 42:19 right so you have no autoimmunity but the b test is not functioning this is the cluster two which is insulin deficient diabetes similar to 42:26 what clusters we are seeing with it should still be classified technically as either type 2 or type 1b diabetes but 42:32 again you know uh there is there is a confusion in this category so again it's not a great idea to put it in any of 42:37 those markets and autoimmunity negative and beta cell function is present this is a classical 42:43 type two diamonds so this is i feel this is a better classification of classifying diabetes because 42:49 it gives you some guidance to how you treat this patient right so one two and three categories 42:55 you will treat with insulin third the fourth category you can treat with orality diabetes 43:01 but the fourth category the a negative beta positive is the category which is the most likely to see in clinical 43:07 practice these are the most common patients right so this is the a beta classification of diabetes 43:13 now so this was the first part of the talk that is the pathogenesis but now we'll come to the 43:19 more important part of this talk and that is basically the clinical approach the clinical implications of this 43:26 okay so what are the clinical implications of this so first thing you have to see is how do i classify my patient so the 43:33 patient who is in front of me where does this patient fall into 43:38 om lakhani spectrum right that is the question right i'll tell you how you will classify your 43:44 patient right like i said this spectrums are necessary because the treatment that you give to this patient depends on 43:51 where the patient stands in the structure right so you will classify that based on clinical 43:58 cues on a test which we do which is known as mixed meal stimulation test i'll just discuss this and based on autoimmune 44:04 markers now if you have the facilities available for number two and number three great but if you don't have the 44:10 facility for number two and three you don't have a good lab backup you need to rely on clinical cues and that's why it 44:16 is very important to be a clinician it is very important to be something like a sherlock holmes who picks up this little 44:21 signs and then makes the right treatment okay so what are the clinical cues 44:27 so i told you see one end you have insulin resistance other and you have beta cell dysfunction 44:33 what are the clinical markers of insulin resistance what are the clinical matters of markers of beta cell dysfunction so 44:39 clinical markers of beta cell dysfunction is mainly catabolic catabolic means 44:45 breaking down right so the patient with beta cell dysfunction will come to you with history of unintentional weight 44:51 loss they'll come with the three classical piece polyurea polytips of polyphasia 44:56 they'll have fatigue they'll have change in vision and they'll have diabetic ketosis 45:02 so whenever you have any of these features the patient is having beta cell dysfunction which is predominating 45:08 on the other hand a patient who is having insulin resistance which is predominant 45:14 this is a group where you have an anabolic situation where the patient typically has weight gain 45:20 central elephant is the patient will be obese patient will have insulin resistant signs that is acanthosis and aggregates if you see the ultrasound you 45:26 will find fatty liver and if you see the cardiac marker if it is a echocardiography you will have f that is 45:33 heart failure with preserved ejection fraction or often they will have diastolic dysfunction which is remarked in the 45:39 uh or left hypertrophy with diastolic dysfunction which you'll see in the echocardiographic reports so when you 45:44 see this type of picture the patient is in an insulin resistant predominant situation now why you need to 45:50 differentiate this we'll come to this in a minute but this is the group where insulin is the first choice this is a 45:56 group where metformin is the first choice of treatment this is the first important point you need to understand 46:01 so then of course we come to the treatment part so i'll just hold your thought for this for a minute the second thing you 46:07 can do is actually classify the beta cell situation we do a test which is known as mixed meal stimulation test we do this 46:13 in-house in our hospital however you can do it you can develop the same test in your laboratory or in 46:20 your hospital i'll tell you how it is then you know uh see if you have this facility available if you can develop it 46:26 so what you do is first you measure the fasting blood sugar along with the c peptide then you give a liquid meal 46:31 which is a standard meal which only the uh most of these labs i mean most of these uh papers are based 46:37 on sustakal system is basically from nestle it's like your protein x and all that uh but what we use is enshore plus 46:44 powder which is a similar composition but the idea is in fact this is much more easily available in india so ensure 46:50 plus is what we use we give six scoops of this powder in 200 ml of water and after 90 minutes we met measure the 46:57 sugar again along with the c peptide so this is the mixed meal stimulation test now more important is how do you 47:03 interpret so this is our interpretation right uh you know this is not published are in the process 47:09 of publishing this so this is unpublished thing but this is the interpretation which we typically have 47:14 developed and it works perfectly it is very good sensitivity and specificity in our practice right so 47:19 we in fact would are in process of collecting the data and published it so when you find 47:25 the c peptide now remember the c peptide value here i have given it in nanogram per ml some labs give it in millimoles 47:31 per liter so depending on what lab your value is giving you can do the conversion you can see the conversion 47:36 online so fasting if the fasting value of c peptide is less than 0.24 nanogram per 47:41 ml we categorize this as 45 right we'll see this importance of scoring this 47:47 patient is more likely to have type 1 and then you can see the grading 0.24 to 0.6 0.6 to 0.1 a 0.6 to 1 and more than 47:54 one whereas post mean if you have or random in fact if you do a random c peptide 47:59 also so if you don't have lab facilities available for this complicated thing you can do a random scenario so random secretary is less than 0.6 nanogram per 48:06 ml uh again this is score 5 then 0.6 to 1.5 1.5 to 1.8 1.8 3.3 and more than 3.3 48:15 right so this is the idea now you take score of top and bottom and you add it up 48:21 if your score is more than equal to five it is strongly suggestive of type one it is between three to five it is 48:26 suggestive of type one so and zero to three unlikely to be type one but needs a close follow-up and zero means it is 48:32 not type one so typically if you find the c peptide value fasting less than point two four automatically 48:38 it is tight one but if you find a random opposed to c peptide less than point six automatically label that as type one 48:44 right or insulin deficient i'm not saying type one again remember see i again i am you know unfortunately miss classifying 48:50 my own way basically you have beta cell dysfunction right so this is what it is 48:55 okay so if you have value more than five the patient has b test dysfunction and this patient 49:00 requires insulin okay going ahead what so now the importance comes of what 49:06 treatment to use the third parameter of course you know i have not made a slide for this but the third one was autoimmune markers autoimmune markers 49:13 you need to test the only autoimmune muscle you need to test in an adult is guide 65 antibody this is the only 49:19 antibody which survives up to little food the other antibodies will most likely be negative but in children you 49:24 need to lose multiple antibodies you have gas 65 antibody you have ia2 antibody you have znt eight antibody and 49:30 you have iaa antibody and these are available as a package from some of these labs or you can individually order 49:36 these depending on the clinical situation but one you must insist in all patients is get 65 antibody or nt guide 49:43 antibody which is available in most of the good labs okay so now the question comes what was 49:50 the need to classify the reason is you need to classify this in this way or you need to spectrumize it in this way 49:56 because you need to understand how to treat it right so whenever you have a patient in a catabolic situation 50:04 when you have a patient who is having beta self predominant features like we discuss the patient has 50:12 weight loss three ps diabetic ketoacidosis change in vision uh and if you do the lab test and you find the 50:19 total score in the mixed meal stimulation more than equal to five this patient is catabolic if this 50:25 patient definitely requires insulin so insulin 50:30 some of these patients later on you can give cell phone uris if they you know have some beta cell 50:35 residual action and some cases five liters on but overall one thing you should definitely give in this patient 50:41 is insult what about patients who have anabolic features and anabolic features 50:47 you have where you have weight gain central adiposity fpf uh fatty liver these patients require 50:54 metformin or glp analog or sglt right so 51:00 why it is important to see so when you see one end of the spectrum the extreme end of the spectrum where you have 51:05 severe catabolic features insulin the other extreme end of the spectrum where you have severe anabolic future 51:12 well textbooks will say metformin but i feel that metformin and sglt2 should definitely be the starting treatment 51:19 so why it is very important to sub classify to spectrumize this patient is 51:24 because the one end of the spectrum where you have beta cell loss which is predominant this end of the spectrum you 51:30 give this patient insulin the other end of the spectrum where you have insulin resistance which is 51:35 predominating you tend to give metformin and hdl between emitter so this is how you 51:41 you know divide this impact group and in the middle you have more beta cell predominant 51:46 features you have more likely to use insulin paraglitazone sulfalurias when you have more of insulin resistance type 51:53 of features you tend to give more of uh you know glp analogues and so on and so forth of course pyrolytis only can give 51:58 it to both the groups but in early or anabolic features you will not give power glitters on but later on in fact 52:04 particulation basically works by reducing insulin resistance so pilot is only something you can act in both but unfortunately pilot doesn't have their 52:11 own baggage which doesn't make it a very attractive option right more importantly it is important to understand when to use 52:17 insulin so when you have patients with prominent catabolic features when you have beta cell depletion 52:23 features when mixed with stimulation score is more than five definitely more than equal to three consider 52:29 patient with diabetic ketoacidosis and patient with random c types less than 0.6 nanogram per ml you definitely need 52:35 to give this patient answer right finally when not to give hdlt2 this is 52:41 also equally important because sclt2 are now becoming very very popular in clinical practice 52:46 and you need to understand this point very importantly because sometimes if you give a patient with beta cell 52:52 dysfunction just gld to inhibitor you can sometimes trigger the patient going into 52:57 a eu glycemic ketocidosis which is a feared complication in this patient so patients having prominent features of 53:03 catabolism so your patients having features suggestive of meat cell depletion patient having mixed meal 53:08 score of three patient with diabetic resistance less than point six so basically a mirrored this last slide to 53:14 tell you that these patients should not be given sjf22 right rather they should be given 53:20 so to summarize and give you some take home messages first take home message is that the 53:25 unifying theory for pathogen diabetes is the imbalance between insulin resistance 53:31 and beta cell function and the final common pathway or the rate limiting step is still the beta cell 53:38 function and beta cell function drives hyperbarics second hyperglycemia is develops when you have 53:46 insulin resistance more than beta cell dysfunction now this could mean either insulin resistance is higher or beta 53:52 dysfunction is lower or you have both third it is time to revise the 53:57 conventional classification of diabetes and to see diabetes in clinical practice as a spectrum 54:02 and not airtight buckets finally you have mixed wheel stimulation 54:08 is a useful test if you have a fasting c peptide less than 0.24 or random or postmaster stimulation scripted less 54:15 than 0.6 it is suggestive absolute incident efficiency and effective instrument 54:20 point five using the drug with the prominent feature so you have more instrument of metabolic features or more 54:26 anabolic features or more beta cell depression feature and more uh anabolic feature you use the right drug you need 54:32 to see clinically whether the patient is catabolic or anabolic and use the right traction 54:38 finally again you know if you are interested more in endocrinology just like you have this very beautiful netflix 54:44 you have something the which is a written version of matrix you can say to a lot of extent it's our notes in endocrinology app it's really available 54:51 on ios and android you can download these and you'll find a lot of notes on similar topics and other topics in 54:57 endocrinology in very simple question answer format uh written by and if you 55:02 want to contribute to this also please get in touch with us we are open for collaboration also now earlier it was this one-man show but now it's a 55:09 collaborative app so you can get in touch and you can download this 55:15 so thank you for a patient listening and again i thank uh netflix the netflix of 55:21 medicine for this very beautiful opportunity and i hope you learned something very useful 55:27 thank you thank you so much the session was really enlightening for all of us and great 55:34 examples and correlation to uh day-to-day life like making it really easy and simple to understand 55:42 uh so let's start with the uh let's start with the questions we have a 55:47 few questions um sure there is uh dr rahul who's asked 55:53 how steroids cause insulin resistance yeah so uh where steroids actually 56:00 produce hypoglycemia through several mechanisms uh now one of the prominent features so you know again that will be 56:06 a talk in itself but to tell you briefly what steroids do in a chronic situation 56:12 is that they cause the shift of the fat mass so we have the adipocytes which are then moved from 56:18 mainly from the peripheries and activities subcutaneous fat which then goes into the central aspect so you tend 56:24 to develop more visceral adiposity so if you see a patient with cushing syndrome remember you know the stick like figure 56:29 so you have this patient with a central you know obesity but this where the but the peripheries are thin right so that's 56:35 a classical cushioning syndrome so this is what happens when the steroids are given for a long time also glucocorticoids remember it's cortisol 56:41 condition is an actual antibonist to insulin so it suppresses insulin production and even at the receptor level it produces 56:47 insulin resistance so again there are several features by which it kind of uh you know 56:53 produces incident resistance also to some extent it also produces because of dysfunction but again that's minor 56:58 compared to the insulin resistance which you produce thank you so i hope that answers your question 57:04 um so we have another question how good is intermittent fasting for insulin 57:10 resistance yeah so you know uh the interesting thing is now we have a lot of emerging 57:16 data in the importance of circadian rhythm in endocrinology of course we knew that but now we have more data to 57:22 back that up more importantly than intermittent fasting i think you know uh timed meals 57:29 are very important right so eating during the right time during the right day helps you the reason is that when 57:35 you eat at the wrong time you trigger the wrong hormones right so you know uh remember your your 57:42 body hormones runs in a proper rhythm so if you eat at night you are triggering your counter regulatory hormones your 57:48 cortisol and your other counter like glucagon and so on which ideally are not triggered at that point of time during 57:53 the cycle right so this state this produces more problems produces more insulin resistance so in all theoretical 58:00 sense uh intermittent fasting does help to a lot of extent the question right now what we 58:05 don't understand is what type of intermediate fasting you should be doing uh how long should you have a fasting 58:11 period uh what really works what doesn't whether it you know kind of correlates 58:17 with actual clinical hard clinical markers is all developing emerging areas of research but 58:23 having said that i think i'm all for fact of eating during a particular set of time and fasting for a reasonably 58:29 long period of time because that is how your body was really designed to work thank you so much um 58:36 so here's another question what is the mechanism of pathogenesis for gestational diabetes 58:43 yeah so like i said i think we discussed this a bit uh so gestational diabetes what happens is so you have somebody who 58:49 is uh you know as the pregnancy advances so you have these all human placental electrogen and other hormones which are 58:56 released which produce insulin resistance right again obviously there's weight gain also in pregnancy so there 59:01 is insulin resistance which is increased now if your beta cell is able to catch up right so beta cell will produce more 59:06 insulin now if the insulin produced by the beta cell is able to catch up to the insulin resistance which is which 59:11 happens because of uh pregnancy then the patient maintains eukaryotic state but if they are not able to catch up because 59:17 of some maybe a endogenous maybe the patient was already obese and the beta cell was already stressed or the patient 59:23 had some genetic uh predisposition some polymorphic traits because of which the beta cell is not able to catch up to the 59:30 level which you have of insulin resistance then you go on to develop gestation libraries 59:37 hello yeah please call it hello huh please tell something about the modi 59:45 are not given any deeply yeah yeah i think modi we will discuss in a 59:50 separate talk altogether so body is basically uh you know it's a spectrum of genetic or 59:56 monogenic forms of diabetes that is what it is and generally you have depending on what body you are 1:00:02 discussing uh you will have different pathogenic process but all of them ultimately at some extent they uh 1:00:09 have beta cell dysfunction so if you see in our spectrum where it fits it fits into the spectrum of beta cell 1:00:14 dysfunction this beta cell this function is not something which is acute it's a this is an intrinsic beta cell 1:00:19 dysfunction where in certain clinical situations patients go around to develop that now in clinical context when should 1:00:25 we suspect a body very simple if you have a patient with a strong family history of diabetes 1:00:30 going across multiple generations so you know you have a father is diabetic grandfather is diabetic multiple members 1:00:36 of the family are diabetic that's where you think of modi and generally modi patients do not have either features of 1:00:43 type 1 that is you know the catabolic features diabetic ketoacidosis weight loss symptomatic hyperglycemia you don't 1:00:49 have those features nor do they have features of obesity or type 2 diabetes you know like i can 1:00:54 those agricans or fatty liver and so on right so when you have a relatively young patient 1:01:00 with three generation history of diabetes with generally mild hyperglycemia presenting without 1:01:06 any symptoms uh you know this is where you should consider in fact some form of monogenic diabetes and you know you have 1:01:12 now monogenic diabetes panels which are available where you can sense this the importance of classifying a patient as 1:01:18 body is one of course you can do genetic counseling and you know for future generations but also very importantly you can some of these patients respond 1:01:24 very well to cell phone nutrients early on perhaps suvs can be used in some of these patients more safely 1:01:30 and remember these are younger patients again you know there's a risk of being misclassified as type 1 again so this is something you should 1:01:36 but they generally don't develop keto acidosis and again depending on what body you are dealing with you might have other uh organs also being involved 1:01:44 thank you so much for that i hope that answers your question dr ashore yeah i want to ask 1:01:50 is it okay to have a one meal a day or a healthy person 1:01:56 well why not if you can uh you know sustain with one meal a day see uh if you see the human 1:02:03 physiology human physiology was never designed for you know uh having a breakfast and lunch 1:02:09 and dinner or having a meal snack and all that right the body was designed to have 1:02:14 uh food uh which can be stored and used for energy in future 1:02:20 now if you have one meal a day and if you you know uh can kind of have 1:02:26 the uh uh i would say the willpower to not eat any 1:02:32 more time and your caloric intake is reasonable during that one meal 1:02:37 your body stores the required forms of energy and then body uses them in required periods of time now whether 1:02:43 that's healthy or unhealthy i think only a good study of such a thing would be uh able to answer that and the to answer it 1:02:51 in a more broad philosophical sense answer is yes you can very well live the rest of your life by eating one meal a 1:02:57 day as long as you know your nutritional requirements are fulfilled and as long as your body you do not suffer from any 1:03:02 other disease where you know it could potentially interfere with your metabolism but so in most normal human 1:03:09 beings completely fine today yeah one more one more last one 1:03:15 and this recent propaganda that eating smallest amount of sugar also 1:03:22 triggers the same amount of insulin as that of a meal is it true 1:03:29 is it scientific so one should not get anything so in between meals 1:03:35 yeah so uh how much insulin is triggered by a particular meal is what is known as 1:03:41 a glycemic index right so if you have uh you know or how much you know uh sugar 1:03:46 how much insulin you require to counter its hyperglycemic peak that is what is glycemic index so if you take simple 1:03:52 carbohydrates simple carbohydrates tend to have like like your sugar or your glucose and so on fructose they 1:03:58 generally tend to have high glycemic index which means that the sugar which will increase more acutely and to 1:04:04 acutely for this acutely increasing sugar you will actually need to uh you know your body needs to produce more 1:04:09 insulin to counter that and to bring it to a glycemic state so you know obviously uh in that context 1:04:16 uh if you have small frequent meals of simple carbohydrates you are disturbing 1:04:22 your ecosystem more frequently uh leading to more beta cell uh you know stress and obviously whether that goes 1:04:29 on to patient goes on to develop diabetes it's not gonna depend in fact that will depend on person to person your own beta reserve but yes it will 1:04:35 make it bad it's not going to have any uh it's not to help you a lot of context 1:04:40 so generally speaking uh you know it's always a good idea to uh have less number of wheels uh perhaps 1:04:48 more concentrated and have timely means uh in a more shortened period of time 1:04:53 rather than to kind of you know eat keep grazing all throughout the day which i think 1:04:59 would do you no good yeah thank you so much 1:05:09 thank you so much dr pilliam for that um so um thank you so much sir for this 1:05:16 amazing talk uh it was really good and very well explained and we hope to have 1:05:22 you soon again on our platform um uh so pretty soon uh i hope you do come 1:05:28 back to the platform

BEING ATTENDED BY

Dr. Darius Justus & 780 others

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dr. Rohan Desai

Dr. Rohan Desai

MBBS | MBA, IIM-A | Founder & CEO, PlexusMD

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dr. Om Lakhani

Dr. Om Lakhani

Consultant Endocrinologist, Ahmedabad

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dr. Rohan Desai

Dr. Rohan Desai

MBBS | MBA, IIM-A | Founder & CEO, PlexusMD

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dr. Om Lakhani

Dr. Om Lakhani

Consultant Endocrinologist, Ahmedabad

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