Thursday, September 19, 2024 | New York Academy of Medicine (NYAM)
1216 5th Ave, New York, NY 10029
Dr. Jeffrey Mechanick, MD, an endocrinologist at Mount Sinai, presents an innovative approach to addressing abnormal adiposity and its impact on cardiometabolic health. He introduces new terminology and modeling for these metabolic disorders, emphasizing the role of ectopic fat in driving insulin resistance and other cardiovascular diseases. Ectopic fat's presence in organs such as the liver, kidneys, heart, pancreas, and lungs links it to chronic conditions like diabetes, cardiovascular diseases, and respiratory issues. In addition, Mechanick highlights the need for lifestyle interventions, research gaps, and practical application in clinical settings to manage and treat cardiometabolic conditions effectively.
Watch Dr. Jeffrey Mechanick's Presentation Below:
See Dr. Jeffrey Mechanick's Slides Below:
-
Transcript of Dr. Jeffrey Mechanick's Presentation:
[Jeffrey Mechanick] [0.16s] It's good.
[Jeffrey Mechanick] [1.36s] Thank you very much for inviting me.
[Jeffrey Mechanick] [3.68s] My name is Jeff Mechanick.
[Jeffrey Mechanick] [4.80s] I'm an endocrinologist here at Mount Sinai.
[Jeffrey Mechanick] [7.36s] What I'm gonna do is I'm gonna speak on abnormal adiposity, hear my disclosures.
[Jeffrey Mechanick] [12.56s] But I want you to sort of expand, your thinking a little bit.
[Jeffrey Mechanick] [17.80s] I wanna present to you a different lexicon, a different way to think about and and use a different terminology for these metabolic disorders, these chronic metabolic disorders, and specifically the cardiometabolic drivers.
[Jeffrey Mechanick] [35.30s] So there'll be new terms.
[Jeffrey Mechanick] [36.90s] Now the new terms are actually useful.
[Jeffrey Mechanick] [38.82s] They're needed because we have emerging scientific data, and it's hard for them to shoehorn into the terms that we have had before.
[Jeffrey Mechanick] [47.67s] We're gonna start off with reframing, redefining obesity as adiposity based chronic disease.
[Jeffrey Mechanick] [55.67s] Talk about some of the theoretical modeling, the epidemiology, and the mechanisms.
[Jeffrey Mechanick] [60.43s] And then we'll go through a survey of the different forms and types of eutopic and ectopic fat, their correlations with cardiovascular disease.
[Jeffrey Mechanick] [71.47s] But, really, the end game here is to expose to to recognize research gaps, questions without answers, knowledge gaps, answers without awareness, and practice gaps, awareness without action.
[Jeffrey Mechanick] [87.02s] That's what plagues us in the hospital when we're rounding and we're trying to help a patient.
[Jeffrey Mechanick] [94.36s] So the different types of, fat, eutopic in adipose tissue.
[Jeffrey Mechanick] [99.40s] That's fat where it's supposed to be.
[Jeffrey Mechanick] [101.64s] And ectopic, not an adipose tissue.
[Jeffrey Mechanick] [104.56s] Now there's a little bit of a gray area here, but eutopic, we can divide into subcutaneous and, actually, visceral fat.
[Jeffrey Mechanick] [113.13s] The visceral fat surrounding the GI, organs, stomach, liver, intestine, but it's also associated with ectopic fat.
[Jeffrey Mechanick] [121.26s] Now it's the ectopic fat.
[Jeffrey Mechanick] [122.70s] This is where the money is.
[Jeffrey Mechanick] [124.46s] This is where you see the inflammation, the root cause for insulin resistance.
[Jeffrey Mechanick] [130.22s] And not only are you seeing it in the liver, we heard a great talk about the ectopic fat in the liver, but also the kidney.
[Jeffrey Mechanick] [137.36s] A colleague of mine, Dan Einhorn in San Diego, described fatty kidney disease.
[Jeffrey Mechanick] [141.84s] I'll show you a slide on that.
[Jeffrey Mechanick] [143.28s] In the muscle, you'll hear a talk on sarcopenia next.
[Jeffrey Mechanick] [147.48s] In the heart, 4 different areas in the heart, epicardial, pericardial, pericardial, and around the coronary arteries, and also a 5th, intramyocardial.
[Jeffrey Mechanick] [160.06s] These are all playing roles.
[Jeffrey Mechanick] [161.34s] This is sort of the black box we've been looking for to account for a lot of the phenomenon that we had difficulty explaining.
[Jeffrey Mechanick] [168.87s] Pancreatic fat, the lipotoxicity, the beta cell apoptosis, the association of the loss of beta cell reserve that gives you that hyperglycemia in the insulin resistance state, remembering that insulin resistance, you have euglycemia.
[Jeffrey Mechanick] [185.42s] You don't necessarily to have the hyperglycemia and actually also in the lung.
[Jeffrey Mechanick] [190.57s] In the lung, the hyper responsiveness of airways.
[Jeffrey Mechanick] [194.25s] So let's begin with a new concept, which is driver based chronic disease modeling.
[Jeffrey Mechanick] [200.39s] I did a lot of work with network analysis looking at complexity.
[Jeffrey Mechanick] [204.95s] And what what occurred to me is that chronic diseases, which are very complicated, we we all have 3 or more chronic diseases as we get older and a vast number of drivers.
[Jeffrey Mechanick] [217.56s] And in network analysis, there's small world phenomenon.
[Jeffrey Mechanick] [221.17s] There are dominant drivers.
[Jeffrey Mechanick] [223.00s] And the phenotype of the chronic disease can be you you can look at the root cause, which is a dominant driver.
[Jeffrey Mechanick] [230.38s] So to the left, you see adiposity based chronic disease.
[Jeffrey Mechanick] [233.66s] This is what we did differently.
[Jeffrey Mechanick] [235.50s] Instead of defining obesity solely in terms of the BMI, which clearly failed us, right, for a lot of the pitfalls of BMI, body mass index, we expanded it.
[Jeffrey Mechanick] [247.38s] We said you can have abnormal adiposity, not just with increased amount, but abnormal distribution, the ectopic fat, and even abnormal function.
[Jeffrey Mechanick] [256.65s] If adiponectin, leptin ratios, and and CRPs, and a lot of the other inflammatory cytokines are ready for prime time, we would actually have a signature of an abnormal, adipocyte secretome that would define abnormal adiposity.
[Jeffrey Mechanick] [273.29s] And then in the proper context, we get the burden of disease.
[Jeffrey Mechanick] [276.32s] In fact, the European Association For the Study of Obesity adopted our ACE, American Association Clinical Endocrinology, terminology for ABCD.
[Jeffrey Mechanick] [286.74s] A lot of letters here.
[Jeffrey Mechanick] [287.94s] ABCD adiposity based chronic disease.
[Jeffrey Mechanick] [290.82s] We then moved on to DBCD, dysglycemia based chronic disease.
[Jeffrey Mechanick] [296.48s] Group at Mayo, they were they were calling attention to the fact it's not really cost effective to treat prediabetes.
[Jeffrey Mechanick] [302.00s] What are you gonna do?
[Jeffrey Mechanick] [302.72s] Throw metformin on?
[Jeffrey Mechanick] [304.00s] And remember, this is before we had all the CVOT drugs, the GLP ones and s g o SGLT twos.
[Jeffrey Mechanick] [310.90s] But are you gonna start treating with pharmacology just because you had prediabetes?
[Jeffrey Mechanick] [315.86s] The the number of lives saved, the cost effectiveness wasn't really there.
[Jeffrey Mechanick] [320.10s] We redefined it.
[Jeffrey Mechanick] [321.69s] We looked at prediabetes not in isolation, but rather on in a spectrum of insulin resistance to prediabetes to die type 2 diabetes to complications.
[Jeffrey Mechanick] [333.06s] And to the right, we did it for hypertension.
[Jeffrey Mechanick] [336.02s] We have new malnutrition for residual risk and lipid based chronic disease models coming out.
[Jeffrey Mechanick] [343.06s] When we put it all together, this was a double paper in JACC, we build this holistic model of cardiometabolic based chronic disease.
[Jeffrey Mechanick] [351.25s] And to the right, you can see the centrality where it focuses on insulin resistance.
[Jeffrey Mechanick] [357.56s] And you can see where it's shaded in green where you have the abnormal distribution, and that's the atopic fat or the visceral fat.
[Jeffrey Mechanick] [365.02s] So let's just go through a survey of what we're talking about.
[Jeffrey Mechanick] [368.22s] Why do we have increased atopic fat to begin with?
[Jeffrey Mechanick] [372.06s] So Scott Grundy was really one of the first to to look at this and say, when you eat, if you have an unhealthy diet, right, unhealthy lifestyle, all that extra calories and the fat, it's gotta go to subcutaneous tissue.
[Jeffrey Mechanick] [384.70s] At some point, the subcutaneous fat says no more.
[Jeffrey Mechanick] [387.90s] I'm done.
[Jeffrey Mechanick] [388.79s] I'm all tanked up.
[Jeffrey Mechanick] [390.50s] And so the fatty acids have to go somewhere else.
[Jeffrey Mechanick] [393.30s] And you can see to the left, the phenotype if you have a gynoid habitus, and it's in the utopic subcutaneous depot or on the right, an android habitus, more visceral fat, ectopic fat, and that's what's causing the disease.
[Jeffrey Mechanick] [408.69s] It's not just about the BMI.
[Jeffrey Mechanick] [412.54s] Here are some very cool imaging, studies that are done, which really can show you, at least for the heart, the differences between the epicardial fat, adjacent to the myocardium, and then you have the pericardial fat, and then outside the pericardial fat.
[Jeffrey Mechanick] [429.11s] And around the coronary arteries, you have pericoronary adipose tissue.
[Jeffrey Mechanick] [434.49s] And they all correlate with different aspects of metabolic syndrome or cardiometabolic based chronic disease.
[Jeffrey Mechanick] [443.37s] In fact, patients who have visceral adiposity, those are the patients who then have this ectopic fat around the heart, and it correlates with the different cardiovascular diseases that have metabolic drivers.
[Jeffrey Mechanick] [459.52s] Atherosclerosis or coronary artery disease, atrial fibrillation, and heart failure.
[Jeffrey Mechanick] [466.81s] If you look here, you can see that even the pericardial fat is associated with those cardiometabolic diseases, particularly atrial fibrillation.
[Jeffrey Mechanick] [472.76s] Here, you could see some of particularly atrial fibrillation.
[Jeffrey Mechanick] [477.17s] Here, you could see some of the mechanisms.
[Jeffrey Mechanick] [479.49s] The mechanisms involve that adapal kind elaboration of the, epicard of the pericardial fat and, the way it affects reentrant rhythms and atrial fibrillation.
[Jeffrey Mechanick] [492.43s] Can you decrease this epicardial and pericardial fat?
[Jeffrey Mechanick] [496.67s] And you can.
[Jeffrey Mechanick] [497.71s] In fact, lifestyle interventions are always the best.
[Jeffrey Mechanick] [500.75s] If you look at our guidelines and if you look at the mass cell data, the the weight loss and the the dietary manipulations, they're gonna work the best.
[Jeffrey Mechanick] [508.64s] But we have drugs, the TCTs work, and, of course, the GLP ones and the SGLT twos can work.
[Jeffrey Mechanick] [515.20s] There's intramyocardial fat.
[Jeffrey Mechanick] [517.60s] So the coronary heart disease, when the muscle is involved and you see depots of this abnormal fat actually in the muscle, and particularly when it's around the pulmonary veins, that's what's correlating with atrial fibrillation.
[Jeffrey Mechanick] [533.52s] Here you can see to the far left, the massoid.
[Jeffrey Mechanick] [536.32s] In the middle, the fatty kidney disease with the kind of gross picture there of the kidney.
[Jeffrey Mechanick] [541.36s] Right?
[Jeffrey Mechanick] [541.60s] It looks like a butcher had their way with it.
[Jeffrey Mechanick] [543.52s] And then on the right side, you can see pancreatic fat and some of the molecular mechanisms.
[Jeffrey Mechanick] [550.78s] Myosteatosis, a fancy word just for the fat inside the muscle, and this is what you see with the sarcopenia, particularly with neurodegenerative disease and my ocardial dysfunction.
[Jeffrey Mechanick] [563.12s] And then finally, the lipid chaperone molecule fatty acid binding protein 4 playing a central role in ectopic fat in the lungs with reactive airway.
[Jeffrey Mechanick] [573.28s] Let me conclude.
[Jeffrey Mechanick] [574.78s] Research gaps.
[Jeffrey Mechanick] [575.83s] These are the questions without answers.
[Jeffrey Mechanick] [577.58s] We need basic science, preclinical, and clinical studies relating the various aspects of a, b, c, d with cardiometabolic physiology, and we need pragmatic clinical trials, clinical trials that mimic what we actually do in medicine to use these findings, these holistic findings on CAT scan, related to abnormal adiposity and correlate them with the cardiometabolic arrangements.
[Jeffrey Mechanick] [606.63s] We need to teach this.
[Jeffrey Mechanick] [608.08s] We need to teach this to our trainees.
[Jeffrey Mechanick] [610.88s] Get them asking for this information to assist with ABCD decision making.
[Jeffrey Mechanick] [617.22s] And lastly, our practice gaps, which are to include on a routine basis, and this was a comment that was made, in the last, session that we should be using this information routinely, and we should build this imaging infrastructure for fast seal and inexpensive technologies.
[Jeffrey Mechanick] [637.51s] Thank you.
The presentations were hosted by I-ELCAP – The International Early Lung Cancer Action Program.
Comments