How Do You Know if You’re HEALTHY? Cholesterol & Uric Acid LAB TEST Results | Dr. Robert Lustig
الملخص
TLDRLa vidéo traite de l'épidémie croissante de stéatose hépatique non alcoolique (NAFLD) aux États-Unis, affectant environ 45 % des adultes et 25 % des enfants. Avant 1980, cette maladie était quasiment inconnue. Le problème est attribué à un dysfonctionnement métabolique causé par la résistance à l'insuline et la dysfonction mitochondriale. Il est souligné que l'insuline à jeun, l'acide urique et l'ALT sont des indicateurs cruciaux de la santé métabolique. Le glucose à jeun, bien que couramment mesuré, est critiqué pour son manque d'efficacité dans la détection précoce des problèmes métaboliques. De nombreux facteurs sociaux et industriels, y compris des divergences dans les méthodes de test, entravent une meilleure compréhension et gestion du métabolisme des individus. La discussion recommande également un suivi régulier et une mesure précise des marqueurs pertinents pour prévenir des problèmes métaboliques avant qu'ils ne se transforment en conditions plus graves.
الوجبات الجاهزة
- 🍔 45% des Américains, y compris 25% des enfants, ont une stéatose hépatique.
- 🔬 La résistance à l'insuline et les mitochondries défectueuses sont clés dans le dysfonctionnement métabolique.
- ⚠️ Le glucose à jeun est un indicateur tardif et peu efficace de santé métabolique.
- 🧪 L'insuline à jeun est un meilleur indicateur pour évaluer la santé mitochondriale et métabolique.
- 💡 Les niveaux d'acide urique doivent rester bas pour éviter l'hypertension et les maladies métaboliques.
- 📉 Un suivi annuel de l'insuline à jeun est recommandé.
- 👨⚕️ L'interprétation des biomarqueurs est complexe et doit être adaptée à chaque individu.
- 🍖 Réduire la consommation de viande et de sucre pour équilibrer l'acide urique.
- ⏳ Une variation rapide de l'insuline peut indiquer des améliorations ou détériorations rapides de la santé.
- ⚕️ Le glucose à jeun ne suffit pas pour diagnostiquer correctement les problèmes métaboliques.
الجدول الزمني
- 00:00:00 - 00:05:00
45 % des Américains ont un foie gras, 25 % des enfants également. Il ne s'agit pas seulement des adultes ou enfants obèses, mais de la population générale. Avant 1980, cette maladie était inconnue. Cela indique un dysfonctionnement métabolique, notamment une mauvaise utilisation des graisses due à des mitochondries défectueuses et une résistance à l'insuline.
- 00:05:00 - 00:10:00
L'application Levels vise à améliorer la santé des gens, mais comment savoir si l'on s'améliore vraiment ? Il est difficile de mesurer les progrès car la maladie métabolique ne s'installe pas en un jour, et il faut du temps pour renverser la tendance. Il n'existe pas de test unique pour déterminer notre amélioration de santé car tout le monde est différent.
- 00:10:00 - 00:15:00
Les marqueurs courants comme le glucose à jeun et le cholestérol, souvent mesurés lors des examens médicaux, ne suffisent pas. Le glucose à jeun est le pire indicateur car il ne montre que si l'on est diabétique. Et attendre de devenir diabétique, c'est agir trop tard, car la maladie métabolique est déjà installée.
- 00:15:00 - 00:20:00
Le glucose à jeun change en dernier. Le test de tolérance au glucose est censé mesurer la réponse à l'insuline, mais il ne le fait pas efficacement. L'insuline en elle-même peut causer d'autres problèmes, comme favoriser la croissance excessive de tissus et accroître le risque de certains cancers. Ce n'est pas le glucose qui est le véritable problème, mais l'insuline.
- 00:20:00 - 00:25:00
Lors d'un test de tolérance au glucose, deux personnes peuvent avoir des résultats similaires, mais l'une peut produire deux fois plus d'insuline que l'autre, ce qui est un indicateur d'une résistance plus avancée à l'insuline, non révélé par le test lui-même. Ce qui compte vraiment, c'est la capacité de l'organisme à revenir à des niveaux normaux après un pic de glucose.
- 00:25:00 - 00:30:00
Face à un apport en glucose, si je suis sain, l'insuline va aider à réduire le pic. Mais si mon insuline est élevée pour maintenir ce contrôle, même si le glucose reste constant, je suis en danger car c'est l'insuline qui crée les effets néfastes. Un test standard ne mesure pas cela, bien que les petits signes de ralentissement de la baisse du glucose après un pic sont révélateurs.
- 00:30:00 - 00:35:00
Si le glucose met du temps à se normaliser, cela signifie que votre insulinorésistance est haute, un signe de dysfonctionnement mitochondrial. Votre insuline élevée indique que vos cellules ne brûlent pas bien le glucose, signalant que vos mitochondries ne fonctionnent pas bien, souvent à cause de facteurs environnementaux ou alimentaires.
- 00:35:00 - 00:40:00
La sensibilité à l'insuline joue un rôle majeur dans la santé métabolique. S'améliorer par le style de vie peut diminuer significativement l'insuline et améliorer la santé. Cependant, sans intervention continue, les troubles métaboliques peuvent revenir rapidement. Un suivi régulier de l'insuline est utile pour vérifier la réponse aux changements de style de vie.
- 00:40:00 - 00:45:00
L'insuline est le meilleur marqueur actuel de la santé métabolique car elle peut indiquer un dysfonctionnement mitochondrial avant que le glucose ou l'hémoglobine A1c ne changent. Malgré sa valeur, l'assurance ne couvre pas le test d'insuline à jeun en partie à cause de standards de mesure non uniformes et du manque d'intérêt de certains organismes médicaux pour la prévention.
- 00:45:00 - 00:50:00
Les individus ayant une faible insuline à jeun peuvent mieux gérer les pics glycémiques sans effets négatifs à long terme, car une élimination rapide du glucose après un repas est clé. Comprendre ces dynamiques est crucial pour interpréter les résultats de santé, surtout combinés à des graphiques de la glycémie mesurés avec des CGM pour voir les tendances.
- 00:50:00 - 00:55:00
La mesure de l'insuline est sous-utilisée malgré son potentiel à révéler des problèmes métaboliques précoces, parfois même avant des signes cliniques comme l'obésité se manifestent. La résistance à l'insuline peut être présente chez des personnes minces, ce qui rend sa surveillance précieuse pour éviter des complications futures.
- 00:55:00 - 01:00:00
D'autres marqueurs sont essentiels pour une évaluation complète de la santé métabolique, y compris l'acide urique et une analyse détaillée des profils lipidiques comme l'apoB. Les triglycérides sont aussi un indicateur clé de risque cardiovasculaire souvent négligé et ont une corrélation plus forte avec les maladies cardiaques que le LDL.
- 01:00:00 - 01:05:00
Des tests supplémentaires comme l'homocystéine, qui est liée aux maladies cardiaques et d'Alzheimer, et l'évaluation de l'âge épigénétique liée au vieillissement pourraient compléter le panorama de santé. De tels tests pourraient un jour devenir plus courants pour offrir un aperçu profond de la santé personnelle, malgré leur coût actuel.
- 01:05:00 - 01:10:00
Les régimes alimentaires modernes influencent significativement la santé épigénétique et le microbiote intestinal, contribuant aux inflammations. Mesurer l'inflammation systémique, bien que difficile, est possible avec des marqueurs comme le hscrp qui peuvent indiquer des problèmes invisibles mais présents de santé générale.
- 01:10:00 - 01:17:39
En conclusion, optimiser la santé métabolique repose sur la compréhension des interactions complexes entre l'insuline, le glucose, et d'autres biomarqueurs dynamiques. Bien que de nombreuses technologies émergent pour évaluer ces facteurs, leur coût et leur interprétation nécessitent encore des développements.
الخريطة الذهنية
الأسئلة الشائعة
Quels sont les principaux indicateurs de la santé métabolique mentionnés ?
Les principaux indicateurs mentionnés sont l'insuline à jeun, l'acide urique et l'ALT.
Quel pourcentage d'Américains souffre de stéatose hépatique ?
45% de la population américaine, y compris 25% des enfants.
Quand la stéatose hépatique a-t-elle commencé à devenir un problème significatif ?
Elle est devenue significative après 1980.
Pourquoi le glucose à jeun est-il un mauvais indicateur de santé métabolique ?
Parce que c'est le dernier indice à changer en cas de dysfonctionnement métabolique et il manque beaucoup d'autres indicateurs importants.
Quel rôle joue l'acide urique dans le métabolisme ?
L'acide urique est lié à l'hypertension et à la dysfonction mitochondriale, accroissant les risques de maladie métabolique.
Pourquoi l'insuline à jeun est-elle importante ?
Elle indique la fonctionnalité mitochondriale et la santé métabolique plus précisemment que le glucose à jeun.
Quelles sont les causes principales de l'élévation de l'acide urique ?
La consommation excessive de viande et de sucre.
Comment la résistance à l'insuline est-elle liée à la fonction mitochondriale ?
Une résistance à l'insuline indique souvent une dysfonction mitochondriale, car les cellules n'utilisent pas efficacement le glucose.
Quelle est l'opinion sur le test de tolérance au glucose par voie orale ?
Il n'évalue pas directement la réponse à l'insuline et n'est pas le meilleur indicateur de la santé métabolique.
Quelle est la recommandation pour mesurer l'insuline à jeun ?
Il est recommandé de contrôler l'insuline à jeun une fois par an et quatre semaines après un changement de mode de vie.
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- 00:00:0045% of Americans have fatty liver 25% of
- 00:00:03children notice I didn't say obese
- 00:00:06adults or obese children all adults all
- 00:00:09children this is something that didn't
- 00:00:10even exist before 1980 and here we are
- 00:00:14now 45 years later and 45% of the
- 00:00:17population has a disease that we never
- 00:00:19heard of
- 00:00:21before so we know something's going on
- 00:00:24this is a clear indicator of metabolic
- 00:00:27dysfunction a clear indicator of in
- 00:00:30ability to utilize fat because of
- 00:00:33defective mitochondria because of
- 00:00:36insulin resistance so these things all
- 00:00:40go together so your fasting insulin and
- 00:00:43your uric acid and your Al T should all
- 00:00:47line up together because they're all
- 00:00:49part and parcel of the same
- 00:00:51pathophysiologic
- 00:00:53[Music]
- 00:00:58pathway the Genesis of today I'll sort
- 00:01:01of set this up a little bit before we
- 00:01:02get into it the Genesis of this
- 00:01:03conversation is you know levels at its
- 00:01:06core is is an app designed to help
- 00:01:08people get healthier like that's the
- 00:01:10mission cut out everything else we just
- 00:01:12want folks to get healthier my mission
- 00:01:14too but that begs a really key question
- 00:01:17how do you know when you're getting
- 00:01:19healthier how do you know the things
- 00:01:21you're doing are working and it's really
- 00:01:23hard to know you didn't get sick in a
- 00:01:26day you're not going to get better in a
- 00:01:28day and the markers that we look at to
- 00:01:32determine metabolic Health didn't go
- 00:01:34south in a day so they're not going to
- 00:01:36get changed in a day either so this is
- 00:01:39why this is a mess in terms of you know
- 00:01:44people Hawking one idea versus another
- 00:01:48people Hawking One supplement versus
- 00:01:50another people Hawking one lab test
- 00:01:53versus and another um this is a very
- 00:01:57murky area and if there was one test
- 00:02:01that could tell you whether or not you
- 00:02:03were getting healthier or not everybody
- 00:02:05be doing it and they're not because it's
- 00:02:09not that simple different people have
- 00:02:11different problems different people need
- 00:02:13different
- 00:02:14solutions and different people respond
- 00:02:17differently to the different paradigms
- 00:02:20so this is um shall we say a u a mange
- 00:02:25of different ideas and you know I'm
- 00:02:28happy to discuss each of them with you
- 00:02:30for the you know purpose of the audience
- 00:02:33understanding the value of these
- 00:02:35different things but if you think you
- 00:02:37can just go to your doctor and get a
- 00:02:39test you know think again I think that's
- 00:02:42really helpful context and I think I
- 00:02:44think we'll split this into sort of two
- 00:02:46parts one we'll talk about broad set of
- 00:02:48markers and then we're going to we're
- 00:02:50going to narrow in a little bit I think
- 00:02:51on glucose and Insulin because that is
- 00:02:53where a lot of of levels bread and
- 00:02:54butter is and where a lot of our members
- 00:02:57are are measuring or paying attention to
- 00:02:59or maybe visualizing their health or at
- 00:03:01least their metabolic health I think
- 00:03:03that setup is is helpful for getting
- 00:03:06into it that realizing we're not going
- 00:03:08to determine in this conversation here
- 00:03:10are the five key markers well I would
- 00:03:12love that headline as an old magazine
- 00:03:13editor uh we're not going to come out of
- 00:03:15this this conversation with that what I
- 00:03:17think might be helpful is to maybe
- 00:03:20narrow in on some markers that to my
- 00:03:22mind need to have two criteria one is
- 00:03:24that they tell us something about our
- 00:03:26underlying physiology which is to say
- 00:03:28there there's some Clarity in the signal
- 00:03:31um that that relates to something
- 00:03:33happening in our body a process that we
- 00:03:36want to to maybe be working functionally
- 00:03:38and the second is that they're movable
- 00:03:40they're things we can actually do
- 00:03:41something about well and that they're
- 00:03:43tight tradable sure that is that they
- 00:03:45actually you know they're on a scale and
- 00:03:47that they tell you something about
- 00:03:49severity it's not just an onoff type of
- 00:03:52deal you know that there's a a dynamic
- 00:03:56range of whatever the marker is to tell
- 00:03:59you oh you know you're at this level
- 00:04:01you're at that level you're at the worst
- 00:04:02level you know that's very important as
- 00:04:04well and it has to then change with the
- 00:04:07either the worsening or with the
- 00:04:09Improvement right that you know those
- 00:04:11are hard to come by yeah so I think most
- 00:04:14people's interaction with markers with
- 00:04:16biomarkers is if they go to an annual
- 00:04:19physical which so many folks don't but
- 00:04:21if you go to an annual physical you get
- 00:04:23your labs and essentially in there
- 00:04:25you're getting glucose and cholesterol
- 00:04:27right that's that's primarily what's
- 00:04:28being measured yeah and that's about the
- 00:04:29worst thing you can get yeah so let's
- 00:04:31start there tell me what's wrong with
- 00:04:34with that as a sort of core set of
- 00:04:36things maybe what's right with it but
- 00:04:38also what's wrong with it in terms of a
- 00:04:39core set that we're at least checking in
- 00:04:41on annually let's start with glucose
- 00:04:43fasting glucose fasting glucose is the
- 00:04:46single worst thing to measure but it's
- 00:04:49the thing that everyone measures and the
- 00:04:52reason everyone measures is because
- 00:04:53it'll tell you if you have diabetes or
- 00:04:55not and in that way well that's an onoff
- 00:04:59okay if you're fasting blood glucose is
- 00:05:01above 125 you have diabetes if you're
- 00:05:04fasting blood glucose is below 125 you
- 00:05:07don't have diabetes and that's basically
- 00:05:10what the physician you know is drawing
- 00:05:14it for and that's what they're referring
- 00:05:15to and that's what the guidelines
- 00:05:18say and there is so much more
- 00:05:21information to be gained and that is
- 00:05:24just the tip of the iceberg and most
- 00:05:27importantly
- 00:05:29if you're waiting for you to develop
- 00:05:31diabetes you are so far behind the a
- 00:05:34ball okay you have missed the train okay
- 00:05:37Train's pulled out of the station okay
- 00:05:39you are already
- 00:05:41sick so the goal is to catch that way
- 00:05:44before so you go to your physician and
- 00:05:47the physician does your fasting blood
- 00:05:49glucose and it comes out back
- 00:05:53102 and he says well that's fine you're
- 00:05:56far away from 125 no that's not fine at
- 00:05:59all at all in fact let's say you had you
- 00:06:02went and got your fasting blood glucose
- 00:06:04and it was 91 and you say oh you're
- 00:06:07doing great no you're not that's already
- 00:06:10a problem okay it's on the way to
- 00:06:14glucose intolerance it's on the way to
- 00:06:17diabetes it's not there yet but that's
- 00:06:19an early indication so how you read it
- 00:06:24and uh understanding what it means is
- 00:06:28extraordinarily valuable in and of
- 00:06:30itself and it's the last thing to change
- 00:06:34now if you take a look at glucose
- 00:06:36tolerance test fasting glucose glucose
- 00:06:38tolerance test over the last 50
- 00:06:41years the Excursion of the glucose is
- 00:06:46pretty much the same for the last 50
- 00:06:49years but the amount of insulin needed
- 00:06:52to keep you at a normal Excursion has
- 00:06:56gone up two to fourfold and that's a
- 00:06:58sign of chronic metabolic disease that
- 00:07:01is not measured in the fasting blood
- 00:07:03glucose that isn't even measured in the
- 00:07:05glucose tolerance test you're already
- 00:07:08sick and you don't even know it so a
- 00:07:11fasting glucose is by far and way the
- 00:07:15worst metabolic parameter test than you
- 00:07:19can imagine if you're waiting for that
- 00:07:21to change okay you're waiting for a good
- 00:07:24do if you've heard me talk on other
- 00:07:27podcasts before you know that I believe
- 00:07:29that tracking your glucose and
- 00:07:31optimizing your metabolic health is
- 00:07:33really the ultimate life hack we know
- 00:07:36that cravings and mood instability and
- 00:07:38energy levels and weight are all tied to
- 00:07:41our blood sugar levels and of course all
- 00:07:44the downstream chronic diseases that are
- 00:07:47related to blood sugar are things that
- 00:07:49we can really greatly improve our
- 00:07:51chances of avoiding if we keep our blood
- 00:07:53sugar in a healthy and stable level
- 00:07:56throughout our lifetime so I've been
- 00:07:59using ggm now on and off for the past 4
- 00:08:01years since we started levels and I have
- 00:08:03learned so much about my diet and my
- 00:08:05health I've learned the simple swaps
- 00:08:07that keep my blood sugar stable like
- 00:08:09flax crackers instead of wheat-based
- 00:08:12crackers I've learned which fruits work
- 00:08:15best for my blood sugar like I do really
- 00:08:16well with pears and apples and oranges
- 00:08:18and berries but grapes seem to spike my
- 00:08:21blood sugar off the chart I'm also an
- 00:08:23notorious night owl and I've really
- 00:08:25learned with using levels how if I get
- 00:08:28to bed at a reasonable hour and get good
- 00:08:29quality sleep my blood sugar levels are
- 00:08:31so much better and that has been so
- 00:08:33motivating for me on my health Journey
- 00:08:36it's also been helpful for me um in
- 00:08:39terms of keeping my weight at a stable
- 00:08:41level uh much more effortlessly than it
- 00:08:43has been in the past so you can sign up
- 00:08:46for levels at levels. link Health get
- 00:08:50access to a continuous glucose monitor
- 00:08:52and the level software that helps you
- 00:08:54really uh dial into a lot of these
- 00:08:56strategies for your life and your body
- 00:09:00couple things that I want to follow up
- 00:09:01on but but one tell me why the ogtt the
- 00:09:03the oral glucose tolerance test doesn't
- 00:09:05do a good job of capturing that insulin
- 00:09:07response isn't that what it's sort of
- 00:09:09meant to do is to say here's how your
- 00:09:10body responds to a glucose load and and
- 00:09:12that's true how your body responds to a
- 00:09:14glucose load by having to put out more
- 00:09:18insulin to handle it insulin in and of
- 00:09:21itself is part of the problem everyone
- 00:09:25thinks insulin is good because it lowers
- 00:09:27blood glucose well insulin has its own
- 00:09:31negative side effects it is uh a growth
- 00:09:35factor so it causes vascular smooth
- 00:09:38muscle growth like coronary artery
- 00:09:40smooth muscle growth it causes glandular
- 00:09:43growth like for instance breast growth
- 00:09:47and prostate growth so it is a risk
- 00:09:50factor for both breast cancer and
- 00:09:51prostate cancer so things that we
- 00:09:54associate with aging are made worse by
- 00:09:58insulin going up so if you need more
- 00:10:01insulin to do the same job and keep your
- 00:10:05blood glucose
- 00:10:07constant you're not in danger because
- 00:10:10your glucose is rising you're in danger
- 00:10:13because your insulin's rising and that's
- 00:10:15not measured in the glucose tolerance
- 00:10:16test we infer it but you don't know it
- 00:10:21right so two people could essentially
- 00:10:22have the same ogt score but one is
- 00:10:26pumping out twice the amount of insulin
- 00:10:28one is much fur further along in an
- 00:10:30insulin resistant State than the other
- 00:10:32one and that's not going to be revealed
- 00:10:33in that test exactly right so the
- 00:10:36glucose tolerance test is good and
- 00:10:41certainly what we do at levels can glean
- 00:10:44a lot of information from that glucose
- 00:10:46Excursion that will tell you but it's
- 00:10:49not necessarily the amplitude it's not
- 00:10:51necessarily the fasting level and it's
- 00:10:53not even necessarily the peak it's
- 00:10:55actually more how it gets disposed of
- 00:10:58decline downward that's why the curve is
- 00:11:01valuable that's why we do this that's
- 00:11:04why levels exist is because the uh uh
- 00:11:08change from the uh Peak down to Baseline
- 00:11:12has lots of information in it but in
- 00:11:16fact what you really want to know is how
- 00:11:18much insulin did it take to do that and
- 00:11:20how quickly did the insulin clear to
- 00:11:23bring you back to Baseline and you're
- 00:11:25not getting any of that from a standard
- 00:11:28uh fasting glucose or GT is there
- 00:11:30anything this is jumping ahead a little
- 00:11:31bit to where I want to go with some of
- 00:11:33the the Dynamics of a glucose curve um
- 00:11:37but I think it's relevant here what can
- 00:11:39I infer about my insulin sensitivity
- 00:11:42from simply looking at the shape of a
- 00:11:44glucose Spike or a glucose curve right
- 00:11:46so the higher the glucose goes the less
- 00:11:49insulin Reserve you have and the slower
- 00:11:52the glucose return to
- 00:11:55normal the less well insulin's working
- 00:11:58so the more insulin resistance so there
- 00:12:01are two phenomena that you can capture
- 00:12:04but neither of them are direct measures
- 00:12:06so the the height of the glucose
- 00:12:09response basically tells you hey what's
- 00:12:11going on with my beta cell I I should be
- 00:12:13able to keep up with this there must be
- 00:12:16defective Reserve or delayed response
- 00:12:19either way that's a problem of the beta
- 00:12:21cell then how quickly things go back to
- 00:12:25normal if they go back to normal quickly
- 00:12:28that means that insul
- 00:12:30chugging out and it's working and it's
- 00:12:32clearing and everything's fine that
- 00:12:34means you have good beta cell function
- 00:12:37with good insulin
- 00:12:39sensitivity but if you've got a plateau
- 00:12:42and it takes a while for it to come down
- 00:12:45then that's a marker for insulin
- 00:12:47resistance and you couldn't see that
- 00:12:49from a fasting specimen and you may not
- 00:12:53even see it from a 2hour specimen which
- 00:12:55is all that your physician is concerned
- 00:12:58about I'm use the phrase there keep up
- 00:13:00because one of the things I found that I
- 00:13:03I didn't really understand in trying to
- 00:13:05explain even these basic Dynamics is a
- 00:13:07question of timing so a glucose Spike if
- 00:13:10I watch my glucose go up very sharply
- 00:13:11and come back
- 00:13:13down that's at its most core reflection
- 00:13:16of something that I have done right I've
- 00:13:17eaten a High car load there's a bunch of
- 00:13:20glucose now in my blood the cgm's going
- 00:13:23to measure that as a as a peak and then
- 00:13:25it's going to come back down so how much
- 00:13:28of that Spike is the result of what I've
- 00:13:31eaten is directly related to the just
- 00:13:33the amount of carbs I have poured into
- 00:13:34my body and how much is related to my
- 00:13:36insulin response which is another way of
- 00:13:38saying how fast can I expect my insulin
- 00:13:41to actually work and bring it down is
- 00:13:43there a world in which I am so insulin
- 00:13:45sensitive that even if I eat a ho ho I'm
- 00:13:47not going to see a big spike or you will
- 00:13:49you will always see a spike okay you
- 00:13:51will always see a spike um the reason is
- 00:13:54when you uh consume the glucose it will
- 00:13:58go first to the liver you know it will
- 00:14:00be absorbed from the intestine it will
- 00:14:01go via the portal vein to the liver the
- 00:14:04liver will take uh
- 00:14:0720% of that glucose and throw it
- 00:14:11straight into the liver for conversion
- 00:14:13to
- 00:14:14glycogen that means 80% will make it
- 00:14:17past the liver and generate a glucose
- 00:14:20response you will get a glycemic
- 00:14:23Excursion now the beta cell will then
- 00:14:27see that because it's got to go
- 00:14:29circulate in the blood the beta cell
- 00:14:30will see the rise in the glucose and
- 00:14:32will start pumping out insulin saying
- 00:14:34hey I've got to clear this you know this
- 00:14:36is this is not the Baseline let's get
- 00:14:39the glucose back down so you will see a
- 00:14:42glucose Spike no matter what the only
- 00:14:45way to not have a glucose spike is to
- 00:14:47not consume glucose so if you're
- 00:14:49consuming straight fat you know you
- 00:14:52won't see much of a glucose Spike if at
- 00:14:54all uh if you are fasting you won't see
- 00:14:57a glucose Spike but otherwise if you're
- 00:14:59consuming food you're going to see a
- 00:15:01glucose Spike the question is how high
- 00:15:04and how long those are the two questions
- 00:15:07how high tells you what was in that but
- 00:15:10it also tells you whether or not your
- 00:15:12beta cells keeping up and how long
- 00:15:16basically tells you if you're insulin
- 00:15:18resistant so the how high gives you uh
- 00:15:22information about the beta cell how long
- 00:15:25tells you more about the body and in
- 00:15:28terms of that just to keep on this path
- 00:15:29of sort of understanding the the glucose
- 00:15:32curve uh how much can I expect that to
- 00:15:36change as I get more insulin sensitive
- 00:15:38and if I start eating lower carb getting
- 00:15:42my insulin in in a proper place should I
- 00:15:45expect that if I'm eating the same diet
- 00:15:48I'm going to see lower Peaks and I'm
- 00:15:50going to see faster returns right we did
- 00:15:53that study in children and we saw that
- 00:15:56if we Chang the diet we could see
- 00:15:59changes in the glucose area under the
- 00:16:01curve the peak glucose response and the
- 00:16:04insulin sensitivity in 10
- 00:16:07days in children and my colleagues at uh
- 00:16:11San Francisco General did it in adults
- 00:16:13and they saw those same changes in two
- 00:16:17weeks so doesn't take long but you know
- 00:16:21will you see it after one meal unlikely
- 00:16:24will you see it after one day probably
- 00:16:27not you know but 10 days you know most
- 00:16:30people can tough it out for 10 days to
- 00:16:33be able to see something that will uh
- 00:16:35help uh uh shall we say solidify their
- 00:16:39belief in you know making metabolic
- 00:16:42Health changes for the better and then
- 00:16:44if if it can change that quickly to get
- 00:16:46healthier how durable is that change
- 00:16:48then can I can I revert it back to being
- 00:16:50less insulin sensitive by giving up on
- 00:16:52my low carb diet absolutely within two
- 00:16:54weeks so you you but bottom line uh it's
- 00:17:00relatively responsive to changes in diet
- 00:17:03and also by the way changes in exercise
- 00:17:06so if you exercise you will start seeing
- 00:17:08improvements in insulin sensitivity too
- 00:17:10if you stop exercising within two weeks
- 00:17:13you'll be back to Baseline so I would
- 00:17:16say there's a Bas a two week uh uh
- 00:17:20transition from metabolically
- 00:17:23unhealthy to metabolically healthy at
- 00:17:25least as far as glucose Dynamics go and
- 00:17:28we'll come back to insulin for a minute
- 00:17:29because I think we're going to want to
- 00:17:30talk a lot about that as a marker but
- 00:17:33again just on the glucose curve side how
- 00:17:36do you think about glucose spikes like a
- 00:17:39lot of what we've talked about you know
- 00:17:41over the years and I do all the content
- 00:17:43at at levels is uh you know the the
- 00:17:45simplified version is glucose bike bad
- 00:17:47glucose bike unhealthy don't do that
- 00:17:49that's true because it can have
- 00:17:50short-term effects you might feel really
- 00:17:52bad you'll probably have a post you know
- 00:17:53a reactive crash uh also long-term it
- 00:17:56can do damage can cause you to be
- 00:17:58insulin resistant
- 00:17:59can also have some effects on its own
- 00:18:01like gation or or inflammation that just
- 00:18:03extra glucose can be having but in that
- 00:18:06Nuance of what counts as a spike how
- 00:18:08many can I have uh how tall can they be
- 00:18:12these are the questions we get I was
- 00:18:13just looking at some member questions
- 00:18:14this week these are the questions we get
- 00:18:15all the time from people and My worry is
- 00:18:18that in putting out this message I have
- 00:18:20freaked a lot of people out
- 00:18:23about about everything they're eating
- 00:18:25and what I hear from so many of them is
- 00:18:27an anxiety that if I'm not going keto
- 00:18:29I'm screwed and well so I'm curious how
- 00:18:32you think about the the sort of um the
- 00:18:36detriment of a glucose Spike all right
- 00:18:38so I'm going to start with a
- 00:18:41controversial uhh saying we're all GNA
- 00:18:45die okay you're gonna die sometime
- 00:18:48everyone dies and no matter how
- 00:18:51metabolically healthy you are you're
- 00:18:53still going to die now the question is
- 00:18:56when obviously we all want to put it off
- 00:18:59for as long as possible and as George W
- 00:19:02bush famously said we all want to die as
- 00:19:06uh young as late as possible Right for
- 00:19:10for sure and that's why levels does what
- 00:19:12it does and I'm again I'm totally for it
- 00:19:15I'm totally in support of it you're
- 00:19:18going to have glucose spikes you can't
- 00:19:21not have glucose spikes you can't freak
- 00:19:24out about it either if you do now you've
- 00:19:26got something called orthorexia you know
- 00:19:28and you start worrying about actually
- 00:19:30what you're eating all the time now we
- 00:19:33do not want to be contributing to
- 00:19:35orthorexia and you know some people will
- 00:19:39take this information and use it shall
- 00:19:41we say not for good and you know we we
- 00:19:45need to protect against that as much as
- 00:19:47possible so you know I'm here to tell
- 00:19:49you you're going to have spikes the
- 00:19:51question how many spikes well preferably
- 00:19:54three spikes a day called breakfast
- 00:19:56lunch and dinner or May maybe two spikes
- 00:19:59a day you know lunch and dinner do you
- 00:20:02need breakfast I mean that's the concept
- 00:20:04of intermittent fasting and maybe that's
- 00:20:06one of the reasons why intermittent
- 00:20:08fasting works is because you only have
- 00:20:10two spikes we don't know that yet I'm
- 00:20:12you know I'm just throwing it out there
- 00:20:14as a possible we do know that
- 00:20:16intermittent fasting helps if you're
- 00:20:18insulin resistant now the reason I think
- 00:20:21intermittent fasting works is because it
- 00:20:23gives your liver a chance to metabolize
- 00:20:25the fat that built up over the previous
- 00:20:2816 hours hours well that will help your
- 00:20:31Spike because you'll be able to process
- 00:20:33the glucose because you're less insulin
- 00:20:36resistant so these things are all sorry
- 00:20:39these things are all related to each
- 00:20:42other it's not like these things work
- 00:20:44separately they're not in silos so what
- 00:20:47the glucose spike is doing what the
- 00:20:49insulin spike is doing what the fat is
- 00:20:50doing in both the liver and the muscle
- 00:20:53all of these things relate to each other
- 00:20:57now
- 00:20:58if you're going to have a spike you want
- 00:21:00to have a spike that doesn't go to say
- 00:21:061880 or above because that's when the
- 00:21:08kidney starts spilling glucose so that
- 00:21:11causes um uh damage to the kidney unpack
- 00:21:14spilling glucose out of the kidneys for
- 00:21:15a minute for so your kidney resorbs
- 00:21:19glucose so the glucose filters through
- 00:21:22it as blood filters through it and your
- 00:21:25kidney has a method for pulling the
- 00:21:28glucose back into the bloodstream
- 00:21:31instead of it going out in the urine and
- 00:21:33that system works until what's known as
- 00:21:37the TM which is basically the maximum
- 00:21:41amount that you can resorb and that
- 00:21:44occurs at a blood glucose of
- 00:21:46180 milligrams per DL so at 180 you
- 00:21:50start spilling glucose into your urine
- 00:21:52and when you spill glucose you take
- 00:21:54water with it and that dehydrates you
- 00:21:56and that's one of the cardinal signs of
- 00:21:58diabetes is polyurea and polydipsia too
- 00:22:01much peeing too much drinking and
- 00:22:03dehydration so you obviously don't want
- 00:22:05that and in addition the higher the
- 00:22:08blood glucose goes you know it's been uh
- 00:22:12glucose has been equated with like
- 00:22:14grains of sand you can imagine if you
- 00:22:16had grains of sand running through your
- 00:22:19uh you know arteries you know it might
- 00:22:21do some damage like the the finish on
- 00:22:24your you know car when you're out on
- 00:22:26Pacific Coast Highway you know just from
- 00:22:29the sand you know and the saltwater
- 00:22:31hitting your car well if you're running
- 00:22:34around with high blood glucose a lot of
- 00:22:36the time you're going to have some
- 00:22:37endothelial dysfunction and that may be
- 00:22:40actually one of the contributions to
- 00:22:42high blood pressure so um high blood
- 00:22:45pressure can occur due to Sugar dietary
- 00:22:48sugar because of the increase in uric
- 00:22:51acid which reduces uh nitric oxide which
- 00:22:54raises blood pressure or it could be
- 00:22:56because of the endothelial cell dis
- 00:22:58function you can see that in the release
- 00:23:00of a a hormone called enden one that you
- 00:23:04can measure again it's a research test
- 00:23:06for the most part we don't you know do
- 00:23:08that routinely but either one of those
- 00:23:10is a sign of uh arterial damage and
- 00:23:15ultimately uh you know that would
- 00:23:17shorten your lifespan uh it's been shown
- 00:23:20that if you can get your blood pressure
- 00:23:22down by 2 millimeters of mercury you
- 00:23:26have a 10% reduction in risk for stroke
- 00:23:30so even a little change in blood
- 00:23:33pressure has big changes in terms of uh
- 00:23:37vascular health so all of these things
- 00:23:41are related to each other obviously you
- 00:23:43don't want your blood glucose to go
- 00:23:44super high but more importantly you
- 00:23:47don't want it to hang around you want it
- 00:23:49to clear and that is a sign that your
- 00:23:52insulin's working that's a sign of
- 00:23:54insulin sensitivity that's a sign that
- 00:23:56your muscles are working your liver
- 00:23:58working working your whole body is
- 00:23:59working I would say that insulin
- 00:24:02sensitivity is
- 00:24:04the pathogenic factor most associated
- 00:24:09with all of the chronic diseases that we
- 00:24:12have today if there's one thing to fix
- 00:24:15it's your insulin resistance and so then
- 00:24:18the question is okay how do you measure
- 00:24:21that and we'll get to that in just a
- 00:24:23minute yeah I just want to go one step
- 00:24:25further on this story we're talking
- 00:24:27about and I think this is a use framing
- 00:24:29of sort of what's happening to the
- 00:24:30glucose in the body and how it relates
- 00:24:33to the sort of height of the spike so we
- 00:24:35talk about let's say your very let's say
- 00:24:37two people are spiking to
- 00:24:39160 one is uh insulin sensitive and the
- 00:24:43other is less so and so it's taking
- 00:24:45longer to clear it but when we talk
- 00:24:47about clearing where does it go even if
- 00:24:50I'm healthy is there a difference in
- 00:24:52where that glucose goes between the
- 00:24:53insulin sensitive person and the
- 00:24:55non-insulin sensitive person once
- 00:24:56they're back to Baseline has a different
- 00:24:58thing occurred in each one of them
- 00:25:00absolutely so where does it get cleared
- 00:25:03to where does glucose get cleared to
- 00:25:05well every cell in the body uses glucose
- 00:25:07for energy but not every cell in the
- 00:25:10body is responsive to
- 00:25:11insulin okay now every cell has glucose
- 00:25:14Transporters but those glucose
- 00:25:16Transporters are not necessarily insulin
- 00:25:19dependent
- 00:25:20Transporters which glucose Transporters
- 00:25:23are the insulin dependent ones glute
- 00:25:26four so there's glute one glute two all
- 00:25:29the way up to glute
- 00:25:3111 okay 11 different glucose
- 00:25:34Transporters depending on which tissue
- 00:25:36you're talking about fructose by the way
- 00:25:40is handled by glute five and also glute
- 00:25:42seven so the different glucose
- 00:25:45Transporters do different things in
- 00:25:47different tissues like for instance the
- 00:25:49brain uses glute one no other tissue
- 00:25:52uses glute one but glute four is the
- 00:25:55only one that's insulin sensitive so
- 00:25:58where's glute four because if your
- 00:26:01insulin level's high that means that the
- 00:26:03glute four specific tissues are going to
- 00:26:06be influenced the greatest and the
- 00:26:09answer there is your muscle and your fat
- 00:26:13and so you're going to drive energy into
- 00:26:15muscle and fat if you drive energy into
- 00:26:17muscle that your muscle is not using
- 00:26:20you're going to get fat deposition in
- 00:26:22your muscle called intramyocellular
- 00:26:24lipid that's a cardinal feature of
- 00:26:27insulin resistance if you drive the
- 00:26:30glucose into fat cells well the fat cell
- 00:26:33is going to turn that into actual
- 00:26:35adapost tissue it's going to turn it
- 00:26:37into triglyceride in the atopos tissue
- 00:26:40it's got all the enzymes to take glucose
- 00:26:42turn it into fat and so you're going to
- 00:26:44lay down more fat and now you've got
- 00:26:46obesity and of course if it's visceral
- 00:26:49fat you will have insulin resistance yet
- 00:26:52uh worse you know it'll basically be a
- 00:26:55vicious cycle so the higher the insulin
- 00:26:58the more your fat and muscle are going
- 00:27:00to gain fat because of the glute 4
- 00:27:04transporter it's not going to make much
- 00:27:06difference in terms of the glute one the
- 00:27:09glute two the glute three the glute five
- 00:27:11the glute and all the way up to 11 it's
- 00:27:14really going to be that glute four but
- 00:27:17that's what causes the
- 00:27:19illness so getting the insulin down is
- 00:27:24job one and the only way to do that is
- 00:27:27to become insulin sensitive and the only
- 00:27:30way to do that is lifestyle so if it's
- 00:27:34just make sure I understand this so if I
- 00:27:37take in the same amount of glucose um
- 00:27:39but I am insulin
- 00:27:41sensitive what is happening such that
- 00:27:44I'm not getting those fat deposits
- 00:27:45either in my muscular tissue or in the
- 00:27:47adapost tissue that that are all the
- 00:27:50risk if I am insulin sensitive the
- 00:27:53glucose has to go somewhere right if
- 00:27:54I've taken in that amount of glucose
- 00:27:56load if you're insulin sensitive it will
- 00:27:58go into all of your other tissues
- 00:28:00equally and will be burned you know by
- 00:28:04the mitochondria to carbon dioxide and
- 00:28:06ATP and will fuel all of those uh
- 00:28:10metabolic processes and you will
- 00:28:12therefore be metabolically
- 00:28:15healthy as soon as your insulin goes up
- 00:28:19what that's a sign of is the fact that
- 00:28:21you're not burning that glucose to
- 00:28:23carbon dioxide and ATP well okay if
- 00:28:27you're not burning it you've getting a
- 00:28:28backup and you need insulin then to
- 00:28:30clear it what is that saying about your
- 00:28:33cells what that's saying is that the
- 00:28:36mitochondria the little subcellular
- 00:28:39organel in inside each cell the little
- 00:28:41energy burning factories inside each
- 00:28:43cell what it's saying those aren't
- 00:28:45working very well for whatever reason
- 00:28:48those
- 00:28:48mitochondria are fallen behind because
- 00:28:52if they weren't fallen behind your
- 00:28:55insulin wouldn't be high and you'd be
- 00:28:57clearing the glucose well so insulin
- 00:29:02resistance and mitochondrial dysfunction
- 00:29:05are part and parcel of the same
- 00:29:08phenomenon so what that's telling us is
- 00:29:11if you're insulin resistant you've got
- 00:29:13something wrong with your mitochondria
- 00:29:15and you need to step up your
- 00:29:17mitochondria well what's wrong with your
- 00:29:20mitochondria and that's where the whole
- 00:29:22question of our environment starts
- 00:29:25coming in okay so let's go back to this
- 00:29:27question of of timing for a moment
- 00:29:29because I think this is really helpful
- 00:29:30in understanding this this glucose
- 00:29:32journey and then what what I'm seeing
- 00:29:34about this glucose Journey on a glucose
- 00:29:36graph is is telling me so if I am
- 00:29:39healthy I take in a load of glucose I
- 00:29:42see it rise but I'm seeing it clear
- 00:29:44quickly which is a sign that my cells
- 00:29:47are taking it up as efficiently as they
- 00:29:49possibly can it's not then going to be
- 00:29:51deposited in my muscle and fat tissue as
- 00:29:55as fat right so if I see a a long if it
- 00:29:59takes a long time for it to clear that's
- 00:30:02essentially a sign that in other would
- 00:30:05let me see how to phrase this if it's
- 00:30:07being cleared quickly it means it's
- 00:30:08going into the cells if it's not being
- 00:30:10cleared quickly that means it's not
- 00:30:11going into the cells where I want to to
- 00:30:13go and it's going to go into this other
- 00:30:14tissue is that right exactly right
- 00:30:17exactly right the longer it stays in
- 00:30:20your bloodstream the worse off you
- 00:30:23are and you can't learn that from a
- 00:30:25fasting glucose you actually can't even
- 00:30:27learn that from a fasting insulin
- 00:30:29although fasting insulin is a much
- 00:30:31better Arbiter of that because the
- 00:30:34fasting insulin basically tells you how
- 00:30:35well your mitochondria working if your
- 00:30:37mitochondria working your fasting
- 00:30:38insulin's low if your mitochondria not
- 00:30:40working your fasting insulin's high it's
- 00:30:42our best proxy for mitochondrial
- 00:30:44function and so I think that the fasting
- 00:30:48insulin is the single best marker for
- 00:30:52metabolic Health that we could
- 00:30:56order and I
- 00:30:58routinely suggest it and order it on my
- 00:31:02patients and I am trying to get the
- 00:31:05medical profession to you know glom on
- 00:31:08to this idea but I will tell you there
- 00:31:10are super number of
- 00:31:13obstacles one is the insurance industry
- 00:31:16because they don't want to pay for it
- 00:31:18even though it's not expensive runs
- 00:31:20between 12 and $120 medium
- 00:31:23$48 so it's not that expensive so and
- 00:31:27they can learn the patients and the do
- 00:31:29their doctors can learn so much from it
- 00:31:32if they knew how to interpret
- 00:31:34it and of course the food industry food
- 00:31:37industry is not happy about that at all
- 00:31:41because it's one of the ways they get
- 00:31:44away with putting junk in our food
- 00:31:46because if you're fasting insul we're
- 00:31:47going up and the only way to fix it is
- 00:31:49your food they don't want you to know
- 00:31:52and then third the American Diabetes
- 00:31:55Association now you would think that the
- 00:31:58American Diabetes Association would be
- 00:32:00very happy for people to not be insulin
- 00:32:04resistant you would think that that
- 00:32:06would prevent them from getting diabetes
- 00:32:09Well the American Diabetes Association
- 00:32:10is really not into prevention they're
- 00:32:11into treatment they're into pharmacology
- 00:32:14they're into
- 00:32:16Pharmaceuticals because their entire
- 00:32:17budget is basically underwritten by big
- 00:32:21Pharma fact matter is the American
- 00:32:23Diabetes Association says do not draw a
- 00:32:25fasting insulin and that's one of the
- 00:32:27reasons why the way that the insurance
- 00:32:29industry doesn't cover it because the
- 00:32:30Ada says that all right so why do they
- 00:32:33say that two reasons and they're both
- 00:32:35specious they're both wrong first reason
- 00:32:39they
- 00:32:42say the different assays for fasting
- 00:32:44insulin are not standardized across
- 00:32:48platforms so if you get it done at your
- 00:32:50local lab if you get it done at the
- 00:32:52hospital if you get it done you know
- 00:32:53through a send out you know you're going
- 00:32:55to get all different results
- 00:32:58from different assays not standardized
- 00:33:01and there's some truth to that I don't
- 00:33:03even argue that that is true one of the
- 00:33:06reasons that this occurs because it
- 00:33:07ought to be something that you should be
- 00:33:09able to measure easily one of the
- 00:33:11reasons this occurs is because some of
- 00:33:13the cheap assays use uh antibodies use
- 00:33:17basically what's either an radioimmuno
- 00:33:19assay or an Alysa enzyme linked
- 00:33:21immunosorbent assay and so it's looking
- 00:33:24at epitopes it's looking at specific
- 00:33:27areas of molecule to determine whether
- 00:33:30or not the molecule is there or not and
- 00:33:33that determines you know the
- 00:33:35level and that's worked for us for a
- 00:33:37long time but you can have cross
- 00:33:40reactants you can have other peptides or
- 00:33:43proteins that you're measuring in the
- 00:33:44same sample that crossreact with the
- 00:33:47antibody and will give you a
- 00:33:48fictitiously elevated level the most
- 00:33:51common of this is pro-insulin now what's
- 00:33:55pro-insulin you've heard of insulin
- 00:33:56what's pro-insulin
- 00:33:58proinsulin is the peptide that has to be
- 00:34:02cleaved to make insulin so it is a pro
- 00:34:06hormone it is not a hormone you should
- 00:34:10not be releasing pro- insulin you should
- 00:34:13be releasing the mature insulin after
- 00:34:17the C peptide is cleaved out of it now
- 00:34:20there's an enzyme in your beta cells
- 00:34:22that Cleaves that c peptide out of it
- 00:34:24it's called pro hormone convertase one
- 00:34:27well when your beta cells are stressed
- 00:34:30when they're working overtime because
- 00:34:32you're insulin resistant and you then
- 00:34:35have a big glucose
- 00:34:37load you need to bring that glucose down
- 00:34:41and that's insulin's job and that beta
- 00:34:44cell is going to work as hard as it can
- 00:34:46to put out as much as it can and it
- 00:34:48doesn't have time to cleave the piece of
- 00:34:52C peptide out and so it's going to
- 00:34:54release the proinsulin too
- 00:34:58now Pro insulin has only 5% of the
- 00:35:00activity of insulin but basically what
- 00:35:02it's a sign of is beta cell
- 00:35:07exhaustion but it gets measured in the
- 00:35:09insulin assay because proinsulin and
- 00:35:11Insulin look a lot alike so you're
- 00:35:14measuring something that's not insulin
- 00:35:17in the insulin assay and so can throw
- 00:35:19off the assay well the American Diabetes
- 00:35:22Association is saying well then don't
- 00:35:24draw it because it's not necessarily
- 00:35:27measuring what you want to measure and
- 00:35:29that sort of you know at a uh uh shall
- 00:35:33we say at a common sense level sort of
- 00:35:36makes sense but who cares who cares if
- 00:35:41it's high it's a problem irrespective of
- 00:35:44whether you're measuring insulin or
- 00:35:45proinsulin or anything else for that
- 00:35:46matter if it's high it's a problem and
- 00:35:49as long as you're using the same assay
- 00:35:52on the same patient you know over time
- 00:35:56you can still use those to understand
- 00:35:59Dynamic changes so I think that's a
- 00:36:02specious reason that the Ada says don't
- 00:36:05do draw it what's the degree by which
- 00:36:07that Pro insulin can throw off that
- 00:36:09reading are we talking small or quite a
- 00:36:11bit so there we know that there is a
- 00:36:13phenomenon called hyperproinsulinemia
- 00:36:15was uh first uh uh espoused by Dr John S
- 00:36:19yudkin not the John yudkin of sugar Fame
- 00:36:22but his cousin okay John es yudkin
- 00:36:27famous British endocrinologist wonderful
- 00:36:29guy um and he was the one who
- 00:36:31demonstrated this phenomenon called
- 00:36:33hyperproinsulinemia and it is without
- 00:36:35question if you're putting out Pro
- 00:36:37insulin it means you are sick that's a
- 00:36:39bad thing to be doing um so no this it's
- 00:36:43a very real thing uh so that's the first
- 00:36:47reason then the second reason that the
- 00:36:49uh American Diabetes Association says
- 00:36:51don't draw it they say fasting insulin
- 00:36:55levels do not correlate with
- 00:36:58obesity that's exactly right they do
- 00:37:01not they correlate with metabolic health
- 00:37:04because they correlate with
- 00:37:05mitochondrial dysfunction and you can be
- 00:37:07obese and have normal mitochondria and
- 00:37:09you can thin you can be thin and have
- 00:37:12crappy
- 00:37:13mitochondria and the fasting insulin
- 00:37:15will tell you that of course it's not
- 00:37:17correlated with obesity that's exactly
- 00:37:19why you should draw it because it's
- 00:37:20telling you something otherwise you
- 00:37:22could just get on the scale and you find
- 00:37:23out the same thing no no no so the
- 00:37:26reason they say not to draw it is
- 00:37:28exactly the reason to draw it but they
- 00:37:31don't get it so I'm working on them but
- 00:37:33boy oh boy I'll tell you it's like
- 00:37:35pulling teeth what's the just to dig
- 00:37:37into let's dig into insulin as a marker
- 00:37:39a little bit because we do offer it in
- 00:37:40the the blood test you know that that we
- 00:37:43offer we include fasting insulin right
- 00:37:44we do Labs 2.0 and fasting insulin is at
- 00:37:47the front and center of that what's the
- 00:37:49best faith argument for maybe not
- 00:37:53ignoring it entirely but what's the
- 00:37:56context with which I should look at that
- 00:37:58insulin marker how should I understand
- 00:37:59that insulin number in the context of
- 00:38:02the other things that I'm measuring and
- 00:38:03let's let's say for these purposes the
- 00:38:05other things that you would like us to
- 00:38:06measure not just the the things I'm
- 00:38:08getting at my standard physical right so
- 00:38:10fasting insulin is in a dynamic range so
- 00:38:15the lower it
- 00:38:16is the better off you are as long as you
- 00:38:18don't have type 1 diabetes then it'll be
- 00:38:21zero and that would be really bad you
- 00:38:23need some insulin okay otherwise you end
- 00:38:26up in diabetic keto acidosis which will
- 00:38:28kill you pretty quick if you don't do
- 00:38:29something about it and the only
- 00:38:30treatment for that is insulin so you
- 00:38:32always need a little insulin and that's
- 00:38:34one of the reasons why we age because
- 00:38:36you always need a little insulin there's
- 00:38:39no way to do without it all right so but
- 00:38:44the lower it is the more functional it
- 00:38:47is the better off you are and the longer
- 00:38:50you will live so it's one of the best
- 00:38:53longevity markers there is and the great
- 00:38:56thing about it is it will change change
- 00:38:58in two
- 00:38:59weeks now it'll also change back again
- 00:39:02in two weeks you know if you stop you
- 00:39:04know applying you know whatever
- 00:39:06lifestyle modification that you uh uh
- 00:39:09used to get it down so it's a uh you
- 00:39:14know to me fasting insulin is where the
- 00:39:16action is and it's cheap and it's
- 00:39:19available and you can do it tomorrow
- 00:39:22there are even now fasting insulin
- 00:39:25assays you can do at home you don't even
- 00:39:27have to go to your doctor but you know
- 00:39:30they cost money and then the question is
- 00:39:32you know is it reliable and you know
- 00:39:34those are questions that you know are
- 00:39:36yet to be answered for each of the
- 00:39:38different uh uh assays that are out
- 00:39:40there the type of question we get all
- 00:39:42the time when we start talking about
- 00:39:43markers is when results don't line up
- 00:39:47with the story that we are telling right
- 00:39:49with this sort of basic picture of how
- 00:39:51things work and and I won't go through
- 00:39:53all of them because that could be an
- 00:39:54hours long podcast of what if this and
- 00:39:56then that yeah yeah not doing that but
- 00:39:58just to stick to glucose and insulin for
- 00:39:59a minute if my insulin is low and I'll
- 00:40:02be personally here my insulin is low
- 00:40:03it's under two good for you I'm a child
- 00:40:06of the 80s which means I grew up eating
- 00:40:07sugar cereal every morning for breakfast
- 00:40:09for 30 years which means daily and I
- 00:40:11know this now because I have a CGM on I
- 00:40:13would spike my glucose to 200 MH and it
- 00:40:16would come back down and yet in my late
- 00:40:1840s my insulin is under two I'm
- 00:40:21delighted explain how that is to me oh
- 00:40:23it's very simple means that you're
- 00:40:25insulin sensitive now
- 00:40:28and it means you have good beta cell
- 00:40:31reserve and it means you're fine now it
- 00:40:33doesn't mean you were fine when you were
- 00:40:36you know
- 00:40:3612 the fact is we have this pandemic of
- 00:40:41childhood obesity and childhood type two
- 00:40:43diabetes and clearly they're not okay
- 00:40:47the fact that you escaped that you know
- 00:40:50period of you know Froot Loops and
- 00:40:52Captain Crunch and you know crackling
- 00:40:55you o brand you know and
- 00:40:57you know Live to Tell the tale and have
- 00:41:00a fasting insulin now of two you know
- 00:41:03hats off to you I wish I were so lucky
- 00:41:06but that's that's great and it you know
- 00:41:09prends good things for the future if you
- 00:41:11can maintain that so how should I think
- 00:41:13then about my A1C My fasting glucose my
- 00:41:18um average glucose or sort of glucose
- 00:41:20stability if I'm wearing a CGM if those
- 00:41:23are not as I remember my last A1C was
- 00:41:27like borderline pre-diabetes right so I
- 00:41:29look at my insulin I go I'm great walk
- 00:41:31away put the paper down all good nothing
- 00:41:33to worry about here I look at that A1C
- 00:41:35and I go if this weren't a member they
- 00:41:38would be emailing us going that looks
- 00:41:39High what should I do about it right
- 00:41:41well understand that the A1C is not the
- 00:41:44fasting insulin okay they are not
- 00:41:46necessarily the same there are various
- 00:41:49uh uh uh I won't say disorders but
- 00:41:53conditions that can lead to a slightly
- 00:41:55elevated hemoglobin A1 see and it
- 00:41:58doesn't necessarily portend anything bad
- 00:42:01example there's a disorder it's really a
- 00:42:05condition because you needs no treatment
- 00:42:08and has no Downstream side effects this
- 00:42:12uh condition is called Modi 2 m oy2
- 00:42:16mature onset diabetes of Youth 2 now
- 00:42:20Modi is a set of diseases that are all
- 00:42:25genetic defects in the beta cell they're
- 00:42:2714 of them 14 different modies and some
- 00:42:31of them are really bad okay some of them
- 00:42:35will ultimately cause significant
- 00:42:40diabetes very intractable to treatment
- 00:42:43and will ultimately lead to early aging
- 00:42:46and
- 00:42:47death no
- 00:42:49argument Modi
- 00:42:512 is a defect in the sensing of the beta
- 00:42:56cell the level of glucose in the blood
- 00:42:59has to get a little higher before the
- 00:43:01beta cell will start kicking out insulin
- 00:43:04it just basically means that the gain
- 00:43:06has been reset the threshold for
- 00:43:09releasing insulin has been reset so
- 00:43:11these people run higher blood glucoses
- 00:43:14routinely but they still get an insulin
- 00:43:17Spike when their blood glucose goes up
- 00:43:20they still clear glucose just as quickly
- 00:43:22they just run a higher blood glucose so
- 00:43:25they hemoglobin A1c is higher has
- 00:43:29absolutely
- 00:43:31no implications for aging or for
- 00:43:36disease it's just a factitious you know
- 00:43:40it's not spurious because it it makes
- 00:43:42sense but it's a factitious biomarker
- 00:43:46that's out of range and means nothing so
- 00:43:50it only means something if the
- 00:43:54physiology is consistent so if you have
- 00:43:57a high fasting insulin and a high
- 00:43:59glucose and a high1 A1c that means
- 00:44:02something because they're all going in
- 00:44:04the same direction so you can point to
- 00:44:06the pathophysiology and say yeah that's
- 00:44:08what's going on we need to do something
- 00:44:09about that but if you see one lab test
- 00:44:12that's out of whack and it doesn't make
- 00:44:14sense with all the others that are in
- 00:44:16the same
- 00:44:17pathway probably best to ignore it or
- 00:44:20possibly it's even lab error maybe it
- 00:44:22needs to be redrawn remember that F all
- 00:44:255% of all lab tests are
- 00:44:28errors that's exactly what I was just
- 00:44:30gonna ask is how reliable Labs tend to
- 00:44:32be in general and does it vary among
- 00:44:34markers or the some we can trust more
- 00:44:35than others it depends on the marker
- 00:44:38yeah so some are much tighter than
- 00:44:40others like glucose is a pretty tight
- 00:44:43one okay although CGM glucose has a much
- 00:44:47wider variation than lab glucose so you
- 00:44:50know we need to keep that in in mind but
- 00:44:52some of the other assays you know there
- 00:44:54are things that can interfere with it
- 00:44:57hey you know somebody spits in the tube
- 00:44:59you know there's there's all sorts of
- 00:45:02you know stuff that goes on in
- 00:45:03Laboratories and I know because I used
- 00:45:05to work in a laboratory and you know you
- 00:45:08do the best you can but you know stuff
- 00:45:10happens so given
- 00:45:12how how rapidly insulin can change for
- 00:45:15instance in response to our lifestyle
- 00:45:17and what we're doing how often should we
- 00:45:19be testing it how frequently should I
- 00:45:21look at my insulin to understand let's
- 00:45:23just focus on metabolic health for now
- 00:45:25and we'll get back to the sort of
- 00:45:26broader Health marker but how should I
- 00:45:28keep a pulse on my metabolic Health what
- 00:45:31are the things I can be looking at
- 00:45:33personally I think that everyone should
- 00:45:35get their fasting insulin done once a
- 00:45:37year along with their standard lab draw
- 00:45:40but they need then to be fasting because
- 00:45:42if you're not fasting you don't know
- 00:45:44where you are on the insulin curve and
- 00:45:45then it's useless but if you're fasting
- 00:45:48then you should get it done once a year
- 00:45:50and if you're changing diet or exercise
- 00:45:52or you know some lifestyle or
- 00:45:54environmental intervention that you
- 00:45:56think is going to improve metabolic
- 00:45:57health I would strongly suggest getting
- 00:46:00a second fasting
- 00:46:02insulin 4 weeks after the change so that
- 00:46:05you can monitor it know that you're
- 00:46:07doing the right thing that that the
- 00:46:09fasting insulin is coming down so that
- 00:46:12you will number one be U positively
- 00:46:15reinforced and you know continue to you
- 00:46:18know on your you know weight loss or
- 00:46:20metabolic Health Journey okay and be you
- 00:46:22know rewarded for your efforts and it'll
- 00:46:26um uh give your uh physician a new
- 00:46:29Baseline to work off of so I think that
- 00:46:31you know once a year and four weeks
- 00:46:34after change uh changing your lifestyle
- 00:46:37and how should I read it then in
- 00:46:39conjunction with let's say I'm wearing a
- 00:46:40CGM or I occasionally are am wearing a
- 00:46:43CGM how should I think about it in
- 00:46:45conjunction with with the kinds of
- 00:46:47curves that I'm seeing relative to what
- 00:46:49I'm eating and what I'm doing well if
- 00:46:50you're insulin resistant then the thing
- 00:46:52you want to look at is not necessarily
- 00:46:54the peak glucose but you want to how
- 00:46:57quickly it returns to Baseline if it
- 00:47:00returns to Baseline in 30 to 45 minutes
- 00:47:04you're doing great if it takes an
- 00:47:07hour not as great if it takes 90 minutes
- 00:47:12clearly not as great and so you should
- 00:47:14look at your fasting insulin in that
- 00:47:16context if your fasting insulin is say
- 00:47:19above 10 and you're clearing your
- 00:47:22glucose slowly that is you know an hour
- 00:47:26or greater you still have some work to
- 00:47:29do if you're clearing your glucose
- 00:47:32rapidly and your fasting insulin is low
- 00:47:36you're in great shape keep doing it so
- 00:47:40you should look at the trends you should
- 00:47:43look at the
- 00:47:44pathophysiology you should understand
- 00:47:46that each of the markers doesn't exist
- 00:47:49in isolation they are not siloed they
- 00:47:51work together if I have relatively low
- 00:47:55fasting insulin and I'm seeing generally
- 00:47:58a trend of of pretty quick return to
- 00:48:00Baseline am I somebody who can then take
- 00:48:03in more carbs without worrying too much
- 00:48:06about what that that actual glucose I'm
- 00:48:09taking in is going to be what what kind
- 00:48:10of long-term damage that might be
- 00:48:12causing my body can I be more tolerant
- 00:48:14of spiking 50 points as opposed to
- 00:48:16trying to stay under 30 or whatever the
- 00:48:18sort of guidance is yeah absolutely
- 00:48:20because you're clearing it and the
- 00:48:22clearing is much more important than the
- 00:48:23spiking that we're very sure of yeah the
- 00:48:26spiking tells you about Reserve but the
- 00:48:29clearing it tells you about sensitivity
- 00:48:31and the sensitivity is the thing that is
- 00:48:33associated with disease so if I am in
- 00:48:35good metabolic
- 00:48:37Health how do you think about how flat
- 00:48:39my glucose curve should be you mentioned
- 00:48:41earlier that we can expect to see spikes
- 00:48:42or maybe Rises is the word we want to
- 00:48:44use instead three times a day when I eat
- 00:48:47but we also know and we see this in a
- 00:48:48lot of you know our members they're
- 00:48:50trying to eat to keep that glucose line
- 00:48:53as flat as possible how flat do you want
- 00:48:55to see that line it's going to undulate
- 00:48:58all right if it doesn't undulate you
- 00:49:00know that means either you're not
- 00:49:01consuming glucose or you're fasting one
- 00:49:04of the other it's going to it's going to
- 00:49:09change we don't know we don't have the
- 00:49:12data to tell you oh the amount of change
- 00:49:17predicts when you're going to die we
- 00:49:19don't have that right I don't think
- 00:49:21we'll ever have that what I can say is
- 00:49:24the longer it stays up
- 00:49:27the more problem it is that's really
- 00:49:29what I can say you should be able to
- 00:49:32clear your
- 00:49:33glucose within an hour that's what I can
- 00:49:37say now different foods will give you
- 00:49:39different Rises and different foods will
- 00:49:42probably have different effects on how
- 00:49:45fast that glucose gets cleared as well
- 00:49:49those are called craft curves okay kft
- 00:49:52for Dr craft who first utilized them so
- 00:49:55different foods will
- 00:49:57you know provide you with different
- 00:49:58information and that's one of the
- 00:50:00reasons why cgms are so great because
- 00:50:02then you can determine well what gives
- 00:50:04you the lowest glucose Excursion what
- 00:50:07gives you the best craft curve for your
- 00:50:11personal body habitus and your personal
- 00:50:14biochemistry you can get that out of the
- 00:50:19CGM now the craft curve of course
- 00:50:21measures insulin it doesn't measure
- 00:50:24glucose so you're not getting that but
- 00:50:27you're getting a proxy because if you're
- 00:50:29clearing your glucose fast that means
- 00:50:32your insulin's in good shape so you know
- 00:50:35we have to understand what we're
- 00:50:37measuring
- 00:50:38glucose but really what you want to know
- 00:50:40about is the insulin so if I'm having
- 00:50:42those rapid returns to Baseline how much
- 00:50:44do you care about glycemic variability
- 00:50:46over the the course of the day if my
- 00:50:49line is still moving quite a bit but
- 00:50:51it's coming back down or if I'm spiking
- 00:50:53every time I eat not that much as long
- 00:50:55as it's coming down
- 00:50:57if it goes up it goes up if it's coming
- 00:51:00down that means your body's okay
- 00:51:02actually there's one more thing I want
- 00:51:03to follow up on on the uh glucose and
- 00:51:05Insulin side this is maybe a bit of a
- 00:51:07tangent but um I want to go back to
- 00:51:11diabetes we talk about diabetes is is
- 00:51:14diagnosed via glucose right via a
- 00:51:17fasting glucose test or an
- 00:51:19A1C but as I understand that what
- 00:51:21diabetes is describing as a state of
- 00:51:23insulin resistant well not necessarily
- 00:51:26okay type one diabetes is not a state of
- 00:51:28insulin resistance it's a state of
- 00:51:30defective insulin uh insulin Reserve so
- 00:51:34if you can't make insulin doesn't matter
- 00:51:36how sensitive you are so it's a
- 00:51:38combination of the two you know it's
- 00:51:40like two um uh uh uh levers you know
- 00:51:44that are in working in concert with each
- 00:51:47other and the more defective one lever
- 00:51:49is the harder the other one has to work
- 00:51:51in order to keep it uh stable so that's
- 00:51:54why you need both pieces of information
- 00:51:56you need the spike to tell you about the
- 00:51:58reserve you need the uh rate of
- 00:52:01clearance to tell you about the
- 00:52:03sensitivity there's information in both
- 00:52:06of those and they're related to each
- 00:52:07other so why do we diagnose diabetes
- 00:52:10with glucose and not insulin well
- 00:52:12because some people will have high
- 00:52:14insulin for a certain glucose and some
- 00:52:16people will have low insulin for a
- 00:52:17certain glucose where you going to draw
- 00:52:19the line it's not going to tell you and
- 00:52:22in addition because the glucose is you
- 00:52:25know doing damage you know it's
- 00:52:27obviously the thing to measure and in
- 00:52:29addition because your kidney is now
- 00:52:32excreting the glucose you know it's an
- 00:52:34easy to measure in the urine so that's a
- 00:52:39better marker for diabetes but it's not
- 00:52:42necessarily A U biomarker with dynamic
- 00:52:46range for metabolic Health insulin's
- 00:52:49much better for that and because insulin
- 00:52:52changes early and glucose changes late
- 00:52:56like I said said if you're waiting for
- 00:52:57the glucose to change horse is out of
- 00:52:59the barn one more question on Diabetes
- 00:53:01how arbitrary is 125 it's pretty
- 00:53:03arbitrary it depends on where you are in
- 00:53:06the curve if you're at the
- 00:53:08Baseline then 125 is diabetes if you're
- 00:53:13in the middle of metabolizing your meal
- 00:53:15and that's your Peak you're doing great
- 00:53:18you know so a uh a blood glucose out of
- 00:53:22context tells you nothing that's why you
- 00:53:26needed to be fasting but it's the last
- 00:53:29thing to change because your body is
- 00:53:31doing everything it can to maintain a
- 00:53:34normal blood glucose it's the absolute
- 00:53:38last thing to change the hemoglobin A1c
- 00:53:42is the second to last thing to change it
- 00:53:44will start to rise before the fasting
- 00:53:46glucose will so if you've got an
- 00:53:49hemoglobin A1c of
- 00:53:515.4 you've got a little bit of defective
- 00:53:56gluc glucose clearance if it goes to 5.5
- 00:53:59you've got a little bit more defective
- 00:54:02glucose clearance and up and up and up
- 00:54:04until you hit six when now you've got
- 00:54:07pre-diabetes and when it hits 6.5 that's
- 00:54:09full-fledged diabetes so you can
- 00:54:12actually see the problem before the
- 00:54:15fasting glucose changes in the
- 00:54:17hemoglobin A1c but even that is late in
- 00:54:21the
- 00:54:22game the fasting insulin will change
- 00:54:25before that and how do I know that
- 00:54:28because you can go into any metabolic
- 00:54:31syndrome clinic in this country and see
- 00:54:35patients who have normal glucose
- 00:54:37tolerance but are obese and Insulin
- 00:54:40resistant so they are not
- 00:54:44hyperglycemic they do not have an
- 00:54:47abnormal glucose tolerance
- 00:54:50test but they're insulin resistant
- 00:54:53they're fasting insulins High to keep
- 00:54:55them at that glucose level and they are
- 00:54:58already spilling protein in their urine
- 00:55:01they already have metabolic kidney
- 00:55:04disease because the insulin caused the
- 00:55:07metabolic kidney disease not the
- 00:55:10glucose so there are things you can look
- 00:55:13at to tell you as an early Diagnostic
- 00:55:17and I'm actually giving a talk at
- 00:55:18Stanford in two weeks on early
- 00:55:20Diagnostics and fasting insulin is job
- 00:55:23one and do you watch insulin on the way
- 00:55:27down if you're treating a diabetic
- 00:55:29patient and you're trying to get that
- 00:55:31that gluc fasting glucose down are you
- 00:55:33also testing their insulin as you're as
- 00:55:36you're treating them and and expecting
- 00:55:37that to also be coming down how do they
- 00:55:39move on the on the reverse side if
- 00:55:41you're improving their metabolic health
- 00:55:43and their fasting insulin should be
- 00:55:45coming down now if you're giving
- 00:55:48metformin you will be improving insulin
- 00:55:50sensitivity so the fasting insulin
- 00:55:52should come down if you are giving
- 00:55:54thadine diones to improve their diabetes
- 00:55:57their fasting insulin might actually not
- 00:56:00change so it depends on how you're doing
- 00:56:02if you're doing it with diet it
- 00:56:04definitely should be coming down and if
- 00:56:06it's coming down then that's a good
- 00:56:08thing okay so let's leave the world of
- 00:56:10glucose and insulin for a moment so we
- 00:56:11have time for some other markers all
- 00:56:13right you mentioned earlier uric acid
- 00:56:15that's also included in our in our
- 00:56:16current levels Labs
- 00:56:18panel is uric acid fit this criteria
- 00:56:21that we were talking about in terms of a
- 00:56:23marker that reveals something about
- 00:56:24underlying physiology is TI tradable and
- 00:56:27can actually be moved yes um and it's
- 00:56:30also got a dynamic range and it um and
- 00:56:33the higher it is the more problem it is
- 00:56:36so yes and that that's another reason
- 00:56:38why we include uric acid in our
- 00:56:40biomarker panel for just that reason the
- 00:56:43question of course is what does uric
- 00:56:45acid mean people don't even know what it
- 00:56:47means it is a breakdown
- 00:56:51product of energy generation it is a
- 00:56:54breakdown product of a
- 00:56:56ATP so when
- 00:56:59ATP you know the energy is in the
- 00:57:02phosphate bonds when
- 00:57:04ATP Cleaves a phosphate off to generate
- 00:57:08energy it becomes a
- 00:57:11DP adenosine diphosphate so the energy
- 00:57:14gets released you um manufact you know
- 00:57:18it gets used to power molecular Motors
- 00:57:20within the cells so that the cells can
- 00:57:22do their job okay then the adpak goes to
- 00:57:26a a Denine
- 00:57:29monophosphate which then goes to im an
- 00:57:32acetol monophosphate which then finally
- 00:57:35goes to uric acid and uric acid is then
- 00:57:37excreted in the urine so it is a measure
- 00:57:41of how fast your body is generating
- 00:57:46energy so a marker of cellular Health
- 00:57:48marker of cellular
- 00:57:49Health now the problem is that uric acid
- 00:57:55does two
- 00:57:57things that you wish it didn't do one is
- 00:58:01it is the inhibitor of an enzyme in your
- 00:58:04arteries called endothelial nitric oxide
- 00:58:07synthes or
- 00:58:08Enos that's the enzyme that makes nitric
- 00:58:11oxide and nitric oxide is your
- 00:58:12endogenous blood pressure lowerer it's
- 00:58:15the thing that causes your blood vessels
- 00:58:18to relax therefore it's the thing that
- 00:58:20keeps your blood pressure down and so if
- 00:58:23you're inhibiting it it means your blood
- 00:58:25pressure is going to go up so it is a
- 00:58:26primary contributor to
- 00:58:29hypertension well known been known since
- 00:58:331967 that uric acid is a driver of
- 00:58:37hypertension the second thing it
- 00:58:39does and this was work of from Rick
- 00:58:41Johnson from University of
- 00:58:44Colorado he showed that uric acid
- 00:58:47inhibits an enzyme that's necessary for
- 00:58:50mitochondria to do their job called cpt1
- 00:58:55carnitine poid oil transferase one now
- 00:58:58what is that that's an enzyme that
- 00:59:00regenerates this compound in your cells
- 00:59:03called carnitine and carnitine is a
- 00:59:05shuttle mechanism for bringing fatty
- 00:59:08acids into the mitochondria so that they
- 00:59:10can be burned if you don't have enough
- 00:59:12carnitine you can't um uh uh cleave
- 00:59:17fatty acids into two carbon fragments
- 00:59:19and use them for burning in which case
- 00:59:21you end up with fatty liver and so if
- 00:59:24you inhibit CPT one you can't transport
- 00:59:28the fat good reason for fat buildup
- 00:59:30which causes insulin resistance and
- 00:59:33clearly mitochondrial dysfunction
- 00:59:34because it's interfering with ATP
- 00:59:36generation because it's interfering with
- 00:59:37mitochondrial function so keeping your
- 00:59:40uric acid down is super
- 00:59:44important now what makes uric acid go up
- 00:59:48well obviously kidney disease because
- 00:59:50you have to excrete it but like what
- 00:59:53else CU kidney disas you can't do much
- 00:59:57about okay you know at least not not I
- 01:00:00mean you can improve your metabolic
- 01:00:02Health that'll help but it's not like
- 01:00:04you can fix that from you know from one
- 01:00:06day to the next um what makes uric acid
- 01:00:10well two things make uric acid the first
- 01:00:13is
- 01:00:14purines because purines are adenosine
- 01:00:18and guanosine they are nucleic acid
- 01:00:22nucleotides that are in meat so Benjamin
- 01:00:26Franklin knew that his meat habit was
- 01:00:28the cause of his gout okay he wrote an
- 01:00:31Ode to his gout back in
- 01:00:341785 so it's been known for a long time
- 01:00:37that you know um uh uric acid is a
- 01:00:40driver of gout and that uh meat is a
- 01:00:44primary driver of uric acid but the
- 01:00:47other thing that causes uric acid is not
- 01:00:49so welln and it's sugar and why does
- 01:00:55sugar increase uric acid right and
- 01:00:59that's a complicated one but let me
- 01:01:01explain it remember sugar is two
- 01:01:03molecules glucose and fructose the
- 01:01:06glucose will get metabolized in every
- 01:01:08cell in the body fructose only in the
- 01:01:10liver the fructose enters the liver and
- 01:01:14the first thing that happens is that the
- 01:01:17fructose gets phosphorated a phosphate
- 01:01:19is added to the fructose so it can then
- 01:01:22go on its biochemical journey to either
- 01:01:25energy uh utilization or more likely fat
- 01:01:29storage when it's phosphorilated a
- 01:01:32phosphate has to be given to it well
- 01:01:35where does the phosphate come from it
- 01:01:36comes from ATP so ATP has to go to ADP
- 01:01:40in order to metabolize fructose which
- 01:01:43starts the uric acid you know that's
- 01:01:45what that's the pathway to uric acid so
- 01:01:48sugar consumption increases uric acid
- 01:01:51too so both meat and sugar consumption
- 01:01:54both increase uric acid
- 01:01:57if you want to get your uric acid down
- 01:01:59you have to cut your meat you have to
- 01:02:00cut your sugar consumption it's just
- 01:02:03that simple but because of the effects
- 01:02:06on blood pressure and because of the
- 01:02:08effects on this carnitine transport that
- 01:02:12ultimately leads to mitochondrial
- 01:02:13dysfunction and fat deposition uric acid
- 01:02:17is a bad player in metabolic health and
- 01:02:20the goal is to keep it down all right so
- 01:02:23how down should it be
- 01:02:26if you look at the lab slip it'll tell
- 01:02:29you that the cut off for high uric acid
- 01:02:31is at
- 01:02:33seven that's wrong that's wrong okay the
- 01:02:38cut off should be at
- 01:02:405.5 now why do I say 5.5 and the lab
- 01:02:44slip says seven clearly they know
- 01:02:46something I'm guessing gout is the
- 01:02:47answer well no no no it has to do with
- 01:02:52the um normal distribution has to do
- 01:02:54with the gaussian Curve
- 01:02:56okay so today if you take a 100,000
- 01:03:00quote healthy unquote and we know that
- 01:03:03they're not healthy because 93% of
- 01:03:05Americans manifest some form of
- 01:03:08metabolic dysfunction but they may not
- 01:03:10know it and they say they're healthy
- 01:03:12okay but they go into this you know
- 01:03:14assay
- 01:03:16okay you're going to generate a
- 01:03:18bell-shaped curve and then you get the
- 01:03:21mean and then what we say is two
- 01:03:23standard deviations from the mean that's
- 01:03:26what we consider abnormal you know
- 01:03:28that's just a statistical fudge is two
- 01:03:31standard deviations from the mean so if
- 01:03:33you do that for 100,000 quote normal
- 01:03:37healthy adults who are not
- 01:03:40healthy that number is going to be
- 01:03:43seven but if you did that 50 years ago
- 01:03:48the number would have been
- 01:03:505.5 and the reason is because we were
- 01:03:52healthy then and we're not healthy now
- 01:03:55the entire
- 01:03:56bell-shaped curve has shifted to the
- 01:03:59right and of course there's no way to
- 01:04:01know that just doing that today you have
- 01:04:04to actually look at what happened before
- 01:04:06to show that and we have so this is true
- 01:04:10for insulin this is true for uric acid
- 01:04:15you know it's it's true across the board
- 01:04:18for you know hosts of things it's true
- 01:04:21for alt which is a liver function test
- 01:04:25okay because everyone has fatty liver
- 01:04:26now 45% of Americans have fatty liver
- 01:04:2925% of children notice I didn't say
- 01:04:32obese adults or obese children all
- 01:04:34adults all children this is something
- 01:04:37that didn't even exist before
- 01:04:391980 and here we are now 45 years later
- 01:04:43and 45% of the population has a disease
- 01:04:46that we never heard of
- 01:04:48before so we know something's going on
- 01:04:51this is a clear indicator of metabolic
- 01:04:54dysfunction a clear indicator of
- 01:04:57inability to utilize fat because of
- 01:05:00defective mitochondria because of
- 01:05:04insulin resistance so these things all
- 01:05:07go together so you're fasting insulin
- 01:05:10and your uric acid and your alt should
- 01:05:14all line up together because they're all
- 01:05:16part and parcel of the same
- 01:05:19pathophysiologic pathway so maybe let's
- 01:05:22wrap this up by coming back to where we
- 01:05:24started which is what is our our set of
- 01:05:26markers what kinds of things we want to
- 01:05:28look at we've talked about insulin a lot
- 01:05:30that being a really key one we've talked
- 01:05:31about uric acid which I think is is
- 01:05:33still pretty much on the fringes of what
- 01:05:35people are are measuring um we talked
- 01:05:38about some some way of looking at
- 01:05:41glucose in relation to your insulin
- 01:05:42whether it's with the CGM or whether
- 01:05:44it's with testing what else do you want
- 01:05:46to see what El what other markers fit
- 01:05:48these criteria we've talked about and
- 01:05:50give us some indication of our health so
- 01:05:51you had mentioned cholesterol at the
- 01:05:53very beginning let's turn to cholesterol
- 01:05:56for a minute everyone thinks cholesterol
- 01:05:58is
- 01:05:59important it's not okay now there are
- 01:06:03different kinds of cholesterols and some
- 01:06:05of them are important but the total
- 01:06:07cholesterol doesn't tell you that so the
- 01:06:10amount of cholesterol on the side of the
- 01:06:12of the package they took it off because
- 01:06:15they know the FDA knows that's not
- 01:06:18valuable that's number one number two
- 01:06:21your total cholesterol on your lab slip
- 01:06:23is not valuable it shouldn't even be
- 01:06:25listed because all it does is confuse
- 01:06:28people and it's
- 01:06:30spous so what does matter well there's
- 01:06:32this thing called LDL does that matter
- 01:06:35and the answer is no it doesn't matter
- 01:06:38either and here's why because there's
- 01:06:40not one LDL there's two and the LDL on
- 01:06:43the lab slip measures both at the same
- 01:06:45time and they're not the same now if we
- 01:06:48had a way of separating and we do the
- 01:06:51two different ldls you can actually
- 01:06:53learn something so that's called a VAP
- 01:06:56analysis or lipoprotein electropheresis
- 01:06:59where you basically can distinguish the
- 01:07:04LDL that causes heart disease called
- 01:07:05small dense LDL from the LDL that
- 01:07:08doesn't cause heart disease which is
- 01:07:09called large buoyant LDL then you can
- 01:07:12learn something but you Insurance isn't
- 01:07:15paying for that that's a $500 test to
- 01:07:18figure that out so people don't know now
- 01:07:21if you can afford it great but you know
- 01:07:23that's not helping the masses so we have
- 01:07:26a still have a problem there um
- 01:07:29triglyceride turns out to be a more
- 01:07:33egregious uh lipid than uh LDL ever was
- 01:07:38the hazard risk ratio for LDL and heart
- 01:07:41disease is 1.3 meaning if you have a
- 01:07:43high LDL you have a 30% increased risk
- 01:07:46of having a heart attack whereas the
- 01:07:48hazard risk ratio for triglyceride and
- 01:07:50heart disease is
- 01:07:521.8 so if you have a high triglyceride
- 01:07:55you have 80% increased risk for having a
- 01:07:57heart attack 50% increased over the
- 01:08:02LDL but we don't even talk about it we
- 01:08:05don't you know pay it any heed and there
- 01:08:08are two reasons why first reason is
- 01:08:11because a lot of people get their blood
- 01:08:12drawn not fasting and you need to be
- 01:08:15fasting for triglyceride to mean
- 01:08:16something because as soon as you eat
- 01:08:18your triglycerides go up okay just like
- 01:08:20your you know your glucose and your
- 01:08:22insulin have to be fasting in order to
- 01:08:24mean something
- 01:08:26and number two um the
- 01:08:31triglyceride doesn't just stay
- 01:08:33triglyceride the triglyceride circulates
- 01:08:35in the bloodstream goes to your fat cell
- 01:08:39offloads the lipid into your fat tissue
- 01:08:43and then it becomes the small dense LDL
- 01:08:45so your triglyceride and your small
- 01:08:47dense LDL are related to each other so
- 01:08:50what you care about is your LDL but you
- 01:08:54care about it in the face of your serum
- 01:08:58triglyceride so high LDL low
- 01:09:01triglyceride not a big deal high LDL
- 01:09:04High triglyceride very big deal now at
- 01:09:08levels we understood this and so we are
- 01:09:11not measuring LDL or triglyceride we're
- 01:09:14measuring something called APO APO
- 01:09:16lipoprotein B and the reason it's
- 01:09:18because LDL and triglyceride both have
- 01:09:19aob B Because one's an evolution of the
- 01:09:23other and so that's a way of figuring it
- 01:09:26out so that's another reason why Labs
- 01:09:282.0 for levels includes apob as one of
- 01:09:32the
- 01:09:33markers okay so that's basically what
- 01:09:37levels is doing right now with tests
- 01:09:40that are normally and routinely
- 01:09:43available and coverable by
- 01:09:46insurance is that all are there other
- 01:09:50tests are there things that we could get
- 01:09:53that would give us information as well
- 01:09:55well and the answer is yeah there are
- 01:09:57there are let me give you an example
- 01:10:00there's a test called homosysteine
- 01:10:03now we are not getting it now turns out
- 01:10:07homocysteine is a metabolic metabolite
- 01:10:11of
- 01:10:12protein it go it's part of the TCA cycle
- 01:10:16but it's also in the protein cycle and
- 01:10:19it is responsive to B vitamins and
- 01:10:23omega-3 fatty acids
- 01:10:26when your B vitamin deficient and when
- 01:10:27you're omega-3 fatty acid deficient your
- 01:10:29homocysteine goes up and it turns out
- 01:10:32homocysteine
- 01:10:33levels predict cardiovascular disease
- 01:10:37and heart attack as well and now we've
- 01:10:39also learned that homocysteine levels
- 01:10:41also predict Alzheimer's disease now
- 01:10:43we've known for years about a disease
- 01:10:46called homoy
- 01:10:47Uria this is a disorder of the enzyme
- 01:10:51that clears homocysteine in the body if
- 01:10:54you have this
- 01:10:55disease you're tall and you're actually
- 01:10:59kind of gangly and you're mentally
- 01:11:02and you get very early heart
- 01:11:05disease it's a disease I used to take
- 01:11:07care of as a pediatric
- 01:11:09endocrinologist well people have now
- 01:11:11done a lot of work on whether or not
- 01:11:13that homocysteine was the cause of the
- 01:11:15mental retardation and the cause of the
- 01:11:18heart disease and we Now understand that
- 01:11:20that is a primary risk factor it's part
- 01:11:23of the pathogenesis
- 01:11:25and it may even be part of the
- 01:11:26pathogenesis of Alzheimer's
- 01:11:29routinely so could we get total homoy in
- 01:11:34our patients and learn something about
- 01:11:36their metabolic status and would that be
- 01:11:40fixable and the answer is yes it's also
- 01:11:43on a dynamic range and it's also
- 01:11:46modulable and it's also um uh you know
- 01:11:50it means
- 01:11:51something but it's not covered by
- 01:11:53insurance today should that change I
- 01:11:56think so so that's an example what other
- 01:11:59tests could you do that would be
- 01:12:03valuable one of the uh Cardinal features
- 01:12:07of Aging is methylation so your DNA gets
- 01:12:13methylated and the longer you live the
- 01:12:16more methylated your DNA gets well it
- 01:12:18turns out the degree of methylation
- 01:12:22predicts the degree of Aging
- 01:12:25you can measure methylation status by
- 01:12:29measuring something we now have a test
- 01:12:31for called epigenetic
- 01:12:33age can you measure epigenetic age yeah
- 01:12:37but insurance not paying for it it's
- 01:12:39relatively still expensive um our
- 01:12:42colleague David Sinclair offers u a
- 01:12:45methylation test uh it's known as the
- 01:12:48denan pace method and you can determine
- 01:12:51that and we know from other studies like
- 01:12:54for inance is my colleague Bruce
- 01:12:56blumberg at UC Irvine has shown that the
- 01:12:59methylation status of an enzyme called
- 01:13:03insulin degrading enzyme predicts
- 01:13:06insulin
- 01:13:08resistance because you can't clear the
- 01:13:10insulin because of its methylation
- 01:13:13status and that that is a primary
- 01:13:15Hallmark of obesity and
- 01:13:18aging so the problem with the denan pace
- 01:13:21is you have to chop up all the DNA so
- 01:13:24you don't know which enzyme it's with or
- 01:13:26which Gene it's with so it lacks a
- 01:13:29certain shall we say specificity but it
- 01:13:31gives you a sense of how you're doing
- 01:13:34from an aging standpoint and my
- 01:13:37colleagues at um UC Berkeley and UCSF uh
- 01:13:41Barbara laiah and L Alyssa eel just
- 01:13:43showed a cross-sectional study showing
- 01:13:46that the degree of ultra-processed food
- 01:13:48that you eat predicts your epigenetic
- 01:13:51age compared to your biological age now
- 01:13:54does that mean you could fix your food
- 01:13:56and fix your epigenetic age we don't
- 01:13:58know that yet no one's done that but is
- 01:14:01that something to look at for the future
- 01:14:03and could that ultimately be a good
- 01:14:06marker for us to be able to draw very
- 01:14:09possibly you know that's an excite
- 01:14:11exciting place to go and then the last
- 01:14:14thing is inflammation so the degree of
- 01:14:16inflammation that's going on in the body
- 01:14:19how do you determine that cu the more
- 01:14:21inflammation the sicker you are without
- 01:14:24question and where's the inflammation
- 01:14:25coming from it's almost always coming
- 01:14:27from the gut gut inflammation so are
- 01:14:30there tests for gut inflammation and the
- 01:14:33answer is not good ones unfortunately
- 01:14:36but we can look at systemic inflammation
- 01:14:39we can look at high sensitivity Ser
- 01:14:41active protein so that's a test that's
- 01:14:43immediately available okay doesn't cost
- 01:14:46too much the problem is it doesn't have
- 01:14:49quite the dynamic range that the others
- 01:14:51do it's not quite as good a biomarker
- 01:14:54but it's still tells you whether there's
- 01:14:56inflammation going on or not and so if
- 01:14:59you know that your C HS CRP is low
- 01:15:03that's a good sign it means that you're
- 01:15:04doing something right and if it's high
- 01:15:07it means clearly things are not right
- 01:15:10and you need to start thinking about
- 01:15:12what it is you're eating in order to get
- 01:15:13that hscrp down doesn't tell you what's
- 01:15:16wrong just tells you something's wrong
- 01:15:19so that's another potential test that
- 01:15:21can be added to the armamentarium and
- 01:15:23it's not too expensive and it's
- 01:15:24available now
- 01:15:26so this is an evolution this you know
- 01:15:29we're working on it we're getting there
- 01:15:32you know we need the science in order to
- 01:15:34be able to justify you know the the the
- 01:15:37cost and the expense and certainly the
- 01:15:39insurance coverage because they're not
- 01:15:41going to pay for anything unless it
- 01:15:42works all right so we're still you know
- 01:15:46uh working on those things but for me
- 01:15:50today the things to know are you're
- 01:15:52fasting insulin and your uric acid and
- 01:15:56your
- 01:15:57apob and you know then we can talk about
- 01:16:00you know the the rest the last question
- 01:16:03on this then which I think this leads
- 01:16:04into is you know we do now have
- 01:16:07companies like function Health from our
- 01:16:09friend Dr Heyman and other companies
- 01:16:11like his that are offering these very
- 01:16:13broad arrays of of tests right I think
- 01:16:15they do over a hundred uh annual uh
- 01:16:19markers what do you think about the
- 01:16:20utility of tests like that are there
- 01:16:23things that things that would sort of to
- 01:16:25be on your wish list either because
- 01:16:26they're precursors or because they're a
- 01:16:27good indication that somebody's going to
- 01:16:29get as part of that large set that
- 01:16:31you're just not going to get at your
- 01:16:32doctor setting cost aside right because
- 01:16:34that is the the barrier to those um you
- 01:16:37know getting those kind of large arays
- 01:16:38but if one has the means what do you
- 01:16:40think about people getting that amount
- 01:16:41of data I think it's probably premature
- 01:16:45and the reason is because we don't know
- 01:16:46what to do with it we don't know how to
- 01:16:48analyze it we don't know what goes with
- 01:16:51what pathway because you're trying to
- 01:16:52influence a pathway you're not trying to
- 01:16:54influence a specific
- 01:16:56biomarker okay the biomarker is a marker
- 01:16:58for the pathway and so when we when we
- 01:17:01have some more data and we know that
- 01:17:03those things are actually manipulable
- 01:17:05and that the manipulation actually
- 01:17:07results in clinical
- 01:17:09benefit then I'll be ready to uh to uh
- 01:17:13support those I think it's a little too
- 01:17:14early for those I think that's a little
- 01:17:16premature it's nice to think about it's
- 01:17:19definitely a a hot research topic and
- 01:17:22I'm for that but you know terms of
- 01:17:25Clinic utility I think don't put the
- 01:17:27cart before the horse
- 01:17:30[Music]
- stéatose hépatique
- santé métabolique
- résistance à l'insuline
- biomarqueurs
- insuline à jeun
- acide urique
- ALT
- dysfonction mitochondriale
- diabète
- glucose à jeun