Sleep 2023.02.22 Wojeck
March 11, 2023ID9652
To CiteDCA Citation Guide
- 00:00So I have the extreme pleasure of
- 00:03introducing our Doctor, Brian object today.
- 00:05He's currently an assistant professor at Yale
- 00:08University in the section of endocrinology
- 00:10who recently joined the faculty here.
- 00:13And we are also very fortunate to
- 00:14have him join us in the sleep center
- 00:17where he sees patients as well.
- 00:18He received his medical degree from
- 00:20University of Arizona and his Masters
- 00:22of Public Health from Emory University.
- 00:25He completed his internal medicine
- 00:26residency at Mayo Clinic.
- 00:28He then completed his
- 00:30subspecialty fellowship.
- 00:30And Sleep Medicine at Yale.
- 00:32And then what?
- 00:34Endocrinology captured his interest
- 00:35when he studied insomnia in women and
- 00:38then went into doing endocrinology
- 00:40fellowship at Yale University to combine
- 00:43these two different but interrelated fields.
- 00:45He has additional training in
- 00:47obesity medicine and is a weight
- 00:50management specialist as well.
- 00:51His clinical and research focus is
- 00:53the comprehensive management of the
- 00:55interrelated disease process of diabetes,
- 00:57obesity and sleep disorders specifically.
- 01:01In how treatment for sleep disorders,
- 01:03diabetes and obesity overlap,
- 01:05he also is interested in how new
- 01:07drugs might help treat sleep apnea
- 01:09as well as obesity.
- 01:11He has authored many publications
- 01:12in these topics and has lectured
- 01:14nationally and internationally as well.
- 01:16Thank you for being with us, Doctor Roger.
- 01:18And without further delay,
- 01:19I would like to hand it over to
- 01:21you to share your expertise on
- 01:23sleep diabetes and obesity.
- 01:24Thank you.
- 01:26Thank you for that rousing
- 01:29introduction. My name is Brian.
- 01:31We're going to be talking about
- 01:32sleep, diabetes and obesity.
- 01:34Our goals today are really to understand
- 01:37the prevalence and Physiology of obesity.
- 01:40We're going to talk about what an obesity
- 01:43evaluation looks like and how weight
- 01:45management can affect sleep and vice versa.
- 01:47Seeking to understand the effects of sleep
- 01:50disorders on diabetes. So first of all,
- 01:54obesity is prevalent and the prevalence in
- 01:58the US has been really growing each year.
- 02:01That and it's higher among African Americans,
- 02:03Hispanics, Native Americans and according to
- 02:06the CDC and this is really as of 2018 data,
- 02:1142.4% of adults greater than 20 years
- 02:13old would be classified as obese.
- 02:15It's actually higher now,
- 02:16it's closer to like 46%.
- 02:18So it it is a disease process.
- 02:22That is becoming more prevalent.
- 02:26Now. 200.
- 02:30Chronic diseases have been linked to obesity,
- 02:33and that's not limited,
- 02:35including but not limited to cardiovascular
- 02:38disease on 13 different kinds of cancer,
- 02:40cerebrovascular disease, diabetes,
- 02:43hypertension, asthma, psychiatric disease,
- 02:46PCOS, Nash, and of course.
- 02:50Obstructive sleep apnea.
- 02:51All right.
- 02:52So we'll we'll be talking about all,
- 02:53all of that.
- 02:54But the important piece of this is that
- 02:58obesity is a disease that has many,
- 03:00many complications and treating that
- 03:03disease has kind of far reaching effects.
- 03:08So.
- 03:08Few caveats to first.
- 03:10First of all,
- 03:11let's start talking about how we should view
- 03:14obesity and how we should think about it.
- 03:16We often use BMI.
- 03:18I use BMI.
- 03:20But BMI is really an imperfect measure
- 03:22and a better measures body composition.
- 03:25But often we can't.
- 03:26Do you know a body composition, dexa.
- 03:28So why do I say that?
- 03:30So we have this picture here, right?
- 03:32Of a heavier gentleman of two of
- 03:34two gentlemen that are of the same
- 03:36weight and one has a different fat
- 03:39distribution and one is more muscular.
- 03:41But they might have the same BMI, right?
- 03:43That body composition matters.
- 03:46And how might it be different among people,
- 03:49elderly people?
- 03:50Persons might have more sarcopenia,
- 03:53so they have a little bit more fat mass,
- 03:55a little less muscle.
- 03:58Cardiovascular metabolism and metabolic
- 04:00risk actually also vary by ethnicity.
- 04:03So in the Southeast Asian population
- 04:06because of fat distributions
- 04:08in in that population,
- 04:10we consider those people's overweight
- 04:12at a BMI of 23 actually and we
- 04:15so we start treating treating
- 04:17patients earlier and actually the
- 04:2027 or greater because of
- 04:22different Baptist tributions
- 04:23and why do I say that they have a higher
- 04:26cardiovascular and metabolic risk at.
- 04:28Lower BMI, right?
- 04:30And they have more visceral fat.
- 04:33As far as their distribution
- 04:34at a lower, lower BMI?
- 04:36Higher muscle mass will
- 04:38obviously affect this as well.
- 04:40Waist circumference is also a
- 04:42better measure and and as we as
- 04:46waste circumference increases as
- 04:49does cardiometabolic risk. So.
- 04:53Obesity is a disease.
- 04:55I will convince you or I will
- 04:57try to convince you of that.
- 04:59If we think of obesity as a disease,
- 05:02it is very undertreated and
- 05:04this is a little bit old data.
- 05:06Now this is 2016,
- 05:08but if we think of obesity as a disease.
- 05:12You know, 86% of patients with
- 05:15diabetes were on appropriate
- 05:18medicines for that disease.
- 05:20Less than .5% of patients in
- 05:23this study were on medications
- 05:26to treat obesity and this was
- 05:29retrospective analysis of just
- 05:30prescription audits of patients.
- 05:33So really
- 05:34a lot, lot of patients and
- 05:36obesity as a disease is undertreated.
- 05:42So. Let's talk about why this
- 05:46kind of shift has happened.
- 05:49So fat mass is regulated during development.
- 05:52So as we grow up, as we,
- 05:55as we reach different parts of life,
- 05:57we first in our early age we
- 05:59have kind of baby fat and then we
- 06:02lose that fat and then as we have
- 06:05changes in our body composition.
- 06:08In puberty where we have more,
- 06:10more muscle mass and maybe changes in
- 06:13fat distribution and we kind of see this,
- 06:16you know? Fat free mass changes here
- 06:20and over over the decades and fat mass.
- 06:23So fat mass kind of goes up over
- 06:25time and then fat free mass,
- 06:27it goes up and then eventually
- 06:28kind of goes down as as as we age
- 06:31because we have sarcopenia and
- 06:33increased fat mass with aging.
- 06:34And we also have some body composition
- 06:37changes with menopause and pregnancy
- 06:38and that this is important because it
- 06:40kind of affects our fat mass set point.
- 06:42We'll be talking in detail on what that
- 06:44means and how we should think about all this.
- 06:47So this is.
- 06:47Kind of the first steps, the nitty gritty.
- 06:50All right.
- 06:50So the big piece from this is fat mass
- 06:53is regulated throughout life, right?
- 06:56And then satiety is regulated
- 06:58via hormone signals.
- 07:00And there's two major pathways.
- 07:02I'm going to say them quickly,
- 07:05but the, the,
- 07:06the bigger,
- 07:06biggest idea that you should take from
- 07:08this is that there is a hunger pathway
- 07:11and then there is a satiety
- 07:13pathway. So the hunger pathway
- 07:15is that neuropeptide will NPY.
- 07:18And a goodie related peptide and then
- 07:22POMC cart is this utility pepper,
- 07:24most things work somewhere on
- 07:26that satiety pathway, all right,
- 07:28and we won't get into too much,
- 07:29but as you can see in this slide,
- 07:31there's a lot of different
- 07:32targets that people are looking
- 07:33into to try and affect this.
- 07:37All right. So step one,
- 07:40let me first let's first talk about the old
- 07:44idea that calorie restriction fixes every.
- 07:48Calorie restriction unfortunately does
- 07:50not result in durable weight loss.
- 07:53This is from the diabetes
- 07:55prevention prevention program,
- 07:56which was an RCT to determine whether
- 07:58lifestyle intervention or pharmacologic
- 08:00therapy namely metformin would prevent
- 08:02the delay or onset of diabetes.
- 08:05So you know, you can see that
- 08:07patients that maintained it started
- 08:09on lifestyle did have an initial kind
- 08:12of drop in weight but then it kind
- 08:15of maintained at this metformin.
- 08:17Meager weight loss. So.
- 08:19So calorie restriction alone
- 08:21doesn't have a durable weight loss.
- 08:23With that and we'll talk about why.
- 08:25All right,
- 08:25this goes to the stat mass set point,
- 08:26but we're going to talk about
- 08:28that Physiology.
- 08:28But this is data to show you.
- 08:30And this data,
- 08:31this kind of data has been reproduced
- 08:33with other drugs that namely
- 08:35like things like phentermine,
- 08:36topiramate where.
- 08:38Where simply doing lifestyle reproduction
- 08:41is insufficient and not a durable therapy.
- 08:45Umm.
- 08:46And the the idea is that diets fail
- 08:49because you have counter regulation
- 08:52that maintains that adiposity.
- 08:55Ryan,
- 08:57you just want to come a little
- 08:58closer because you're still
- 09:00coming in and out. No problem.
- 09:03So here's the other here's the next thing
- 09:06that we should kind of think about.
- 09:09If if we could just,
- 09:11if there wasn't a counter regulation,
- 09:13we should be able to just remove fat.
- 09:15This is a study of 32 pre
- 09:18menopausal women 18 to 50 with
- 09:21you know initial BMI of 22 to 27.
- 09:25And then what we find is after
- 09:28liposuction there was a reaccumulation
- 09:31and a fact after 12 months.
- 09:34So liposuction doesn't is
- 09:37not a effective treatment.
- 09:40And so this was liposuction
- 09:41versus no treatment.
- 09:42If if there wasn't a counter regulation
- 09:45liposuction should be effective but
- 09:47it is not these these patients return
- 09:49to their prior fat mass set point.
- 09:54All right. And this is a study I really
- 09:56like or I think is really interesting.
- 09:59Extreme weight loss causes
- 10:01significant counter recognition.
- 10:02This was a study of the
- 10:05biggest loser competition.
- 10:06So which I'm really did extreme weight loss
- 10:09in people that were a class 3 obesity and.
- 10:12So these, these people were studied
- 10:15and they they were evaluated for
- 10:18their resting metabolic rates and
- 10:21what would happened afterwards.
- 10:23So the idea is that everyone has a fat
- 10:26master point and we'll kind of talk
- 10:29about this balance in our next slide.
- 10:32And as we lose weight,
- 10:34our resting metabolic or our
- 10:37basal metabolic rate goes down.
- 10:40Right, because you have to carry less stuff,
- 10:42it takes less energy to live and
- 10:45when it goes down quite quickly.
- 10:47You actually take a little bit of a
- 10:50hit and you see as these patients
- 10:52did to their resting metabolic rate,
- 10:54what's interesting about this study
- 10:56is that five years after the biggest
- 10:58loser competition where they were,
- 11:00you know,
- 11:01incredibly calorie deprived exercising.
- 11:06Exercising to to an extreme amount.
- 11:11They had a lower resting metabolic
- 11:14than they should have five years
- 11:17after the competition.
- 11:19Which is not what you would expect.
- 11:21They they should,
- 11:21they were worse off for the competition,
- 11:23which by conventional logic
- 11:25we should be better, right.
- 11:28So what do we think happened
- 11:30to these patients?
- 11:32Umm.
- 11:32As I mentioned,
- 11:34we have this fat mass set point right?
- 11:38And I've borrowed this from
- 11:40Doctor Lee Kaplan.
- 11:41This is a great slide on so everyone
- 11:43has a certain fat mass set point.
- 11:46And that you know gets dysregulated
- 11:50for lots of proposed reasons.
- 11:51We don't know why.
- 11:52I have my own postulates,
- 11:54but I don't think we have good
- 11:56data to to support that that
- 11:58any any particular theory yet.
- 12:01But we know it gets disregulated.
- 12:04And when we lose weight at a fast rate,
- 12:08our fat mass setpoint stays steady and our.
- 12:13And but our metabolic rate goes down and
- 12:15if we lose weight too quickly or very,
- 12:18very quickly takes a bit of a hit.
- 12:21We were to maintain that weight
- 12:23to kind of equilibrates.
- 12:24But what more often happens is
- 12:26you take a hit to the metabolic
- 12:28rate and patients regain weight
- 12:30and often gain a little bit more.
- 12:32So that conventional thinking,
- 12:34eat less,
- 12:35exercise more just doesn't work
- 12:37because the body defends this fat mass
- 12:40setpoint and the goal of weight management.
- 12:43Is to work on Physiology,
- 12:45all right.
- 12:46And we'll talk about how there
- 12:49are conservative ways and more
- 12:51aggressive ways to do them.
- 12:53So.
- 12:54Let's put obesity in the kind
- 12:56of classical framework we think
- 12:58of other diseases.
- 12:59Primary prevention is really to
- 13:01prevent obesity as a disease, right?
- 13:04We prevent obesity.
- 13:05We certainly will prevent its complications.
- 13:10Secondary,
- 13:10secondary prevention is to prevent
- 13:14the complications of obesity.
- 13:17So we treat the disease of obesity.
- 13:19We evaluate for the complications,
- 13:22such as obstructive sleep apnea.
- 13:24And then we we treat those
- 13:28in tertiary prevention, right?
- 13:29We treat complications of obesity if we find
- 13:32them and hopefully we can prevent them.
- 13:34You know, someone does not
- 13:36have those complications,
- 13:37we can simply treat the primary disease
- 13:40and and not develop those problems.
- 13:44Great, maybe I've convinced you.
- 13:46But how do we, how do we change that fatness?
- 13:49Setpoint. What do we do? All right?
- 13:51Let's talk about conservative things.
- 13:54Simple, simple things, right?
- 13:56So the what? What?
- 13:58We'll kind of.
- 14:01Affect our fat mass set point are things
- 14:04like how how calorie dense our diets are and
- 14:07what what do I mean by that? The goal of.
- 14:12Diet is not to make someone hungry, right?
- 14:16We shouldn't shake life, and all of
- 14:18that is not an effective treatment.
- 14:21Modality, as we just saw in this biggest
- 14:24loser study, are the goal should be
- 14:27to pick foods that are healthful,
- 14:30that are not very calorie dense.
- 14:33That's a really complicated statement.
- 14:35So what's the one thing you can tell
- 14:38your patients eat more vegetables.
- 14:39Very low calorie density.
- 14:42Right. Healthful.
- 14:45Not a lot of satiety with vegetables,
- 14:47but if you shovel enough vegetables in,
- 14:50you actually might have an effect on weight.
- 14:53Umm.
- 14:55Sleep deprivation certainly has an effect.
- 14:57Circadian disruption has an
- 14:59effect and high stress, you know,
- 15:01so and we'll talk about those
- 15:04findings and and why,
- 15:05why that those things might change
- 15:07the fat mass set point.
- 15:09All right.
- 15:11So first of all.
- 15:15Course it does.
- 15:16I don't have to convince anyone here.
- 15:18So this was a look at 718 sleep Diaries
- 15:25in the Wisconsin Sleep cohort and
- 15:28they did vein sampling of growlin and
- 15:31leptin and you'll find that patients
- 15:34that are had a higher BMI had higher
- 15:38levels of brelan and lower levels of
- 15:42leptin and what that means is they.
- 15:44Basically had more of a feeding dry right
- 15:47and that was driven by their sleep,
- 15:50sleep deprivation, right.
- 15:51So these patients that slept
- 15:53less had hormonal changes that
- 15:55pushed their feeding drive up.
- 16:00So this is another study.
- 16:02I really like this.
- 16:03There's a couple of them done by Ken Wright,
- 16:06who's a circadian scientist.
- 16:08And this was a two week long study
- 16:13looking at energy expenditure and ad
- 16:15libitum food intake to assess, you know,
- 16:18energy balance and he also looks at.
- 16:24At different hormones you did vein
- 16:26sampling through this specifically.
- 16:27You know we won't get into the nitty
- 16:30gritty of the different hormones,
- 16:32but the bottom line is he
- 16:33did some vein sampling.
- 16:34So what what he would do is he
- 16:37had a baseline, baseline section,
- 16:39a sleep deprivation section and
- 16:41then like a recovery section, so.
- 16:46So the and he compared
- 16:48patients to themselves.
- 16:49And the the important piece here is that.
- 16:54Energy expenditure. So what?
- 16:55What have, what does what happens?
- 16:57With sleep deprivation,
- 16:58energy expenditure increases,
- 17:00so your metabolic rate increases, however.
- 17:04Patients had higher intake of of foods,
- 17:11right that outpaced.
- 17:13That, that energy expenditure with a
- 17:17preference towards carbs a little bit.
- 17:19And then why did it happen?
- 17:21Well, we thought they found increases
- 17:22in some of the hunger hormones, right?
- 17:25Same thing we saw before,
- 17:26increase in growing, decrease in leptin.
- 17:29So this kind of same consistent signal.
- 17:32All right, so sleep deprivation and
- 17:34sleep quality matter for weight.
- 17:37Any and and acute sleep deprivation.
- 17:41Because this was a short study,
- 17:42we saw this happened very quickly, right.
- 17:45This wasn't years, this was,
- 17:47you know, couple weeks.
- 17:48So,
- 17:49so those kind of acute
- 17:50changes matter for day-to-day.
- 17:55Stress reduction matters, right?
- 17:58Simple things. So this was a a study,
- 18:02a case control study of of the kind
- 18:06of women who had acute stresses in
- 18:08their lives and had acute weight,
- 18:11rapid weight gain around a stressful event.
- 18:16And and looking at you know
- 18:17reference weight non stress related
- 18:19obesity and stress related obesity,
- 18:21this is just to show that there is
- 18:23a what appears to be an etiology of
- 18:26a stress related gain in weight.
- 18:29These patients had 24 hour urinary free,
- 18:31cortisol strong.
- 18:32That were elevated and it was really
- 18:34kind of shown that that obesity was
- 18:37associated with that stress and and
- 18:39that stress increased their cortisol,
- 18:41increase their feeding behavior
- 18:44and what they counted as an event
- 18:46as stress is pregnancy, lactation,
- 18:48miscarriage, death of a family member,
- 18:51job change,
- 18:51smoking cessation and the list
- 18:53kind of went on.
- 18:54The bottom line is that acute stress
- 18:57caused these patients to gain
- 18:59weight and there was a physiologic
- 19:01change in their cortisol.
- 19:04So. There's all these things that
- 19:07affect the fat mass set point.
- 19:09There's a few strategies we
- 19:11talked about that are conservative
- 19:13that might have an effect on it.
- 19:15But you know, everyone kind of has heard
- 19:18that there's new medicines for this too.
- 19:21So why? How do these these things work?
- 19:24What are we doing? Well.
- 19:27Well, take a little bit of a
- 19:29history lesson here, right.
- 19:30There's four things we could do, right.
- 19:33We can, well, I'm sorry,
- 19:36there's two two things we can do.
- 19:37We can either increase exercise
- 19:41and thermogenesis, right.
- 19:42We either increase our metabolic rate or
- 19:46we increase satiety or or quote UN quote,
- 19:49decrease our appetite.
- 19:52Because these are,
- 19:52these are our goals, right?
- 19:54These are our targets is one of these two,
- 19:57but we try to do this first one,
- 20:01increasing exercise or thermogenic.
- 20:02So first of all, increasing exercise.
- 20:07Really effective in your
- 20:0920s as a weight loss target,
- 20:12less effective as we age.
- 20:17Does that make exercise less important?
- 20:19Not at all,
- 20:20but we have to counsel patients about
- 20:23that and what we'll get into the
- 20:25detail the nitty gritty on that as we age.
- 20:27Exercise is good for weight maintenance.
- 20:30Maintaining muscle and bone strength.
- 20:33And and improving metabolic health,
- 20:36but it doesn't cause a lot of weight loss,
- 20:38all right.
- 20:39So it's so although very important
- 20:42part of your plan you have to counsel
- 20:45patients on what that actually does.
- 20:48So what about thermogenesis?
- 20:49Why don't we just give everyone
- 20:51all the thyroid medicine?
- 20:52We can just load everyone up
- 20:54and make some thyrotoxic.
- 20:56Well,
- 20:57we tried that in the 70s with
- 21:00thyroid and DNP. And it harms people.
- 21:02So we don't do that anymore.
- 21:04There are some caveats to that.
- 21:05There's some research trying to learn,
- 21:08looking into how to do this safely.
- 21:09Umm, I am a little bit skeptical of it,
- 21:14but I think maybe we'll be
- 21:15able to do that in the future.
- 21:17But that's really not medicines do anymore.
- 21:20So what our medicines really do.
- 21:23Is the affects the tivity all
- 21:25right and they lower that fat mass
- 21:27set point by affecting satiety?
- 21:33So. When we talk about obesity treatment.
- 21:38It's we finally have medicines
- 21:40that are effective and they're
- 21:41safer than the ones that, you
- 21:43know, we've had in the past.
- 21:45But the effect of all obesity
- 21:47medicines are really variable.
- 21:51So this is the scale trial looking
- 21:54at liraglutide and weight loss.
- 21:57Versus placebo and what you'll see,
- 22:00right, is what what is often
- 22:02called a waterfall plot.
- 22:04Is there's a one, and these are
- 22:05each in each of these little lines.
- 22:07Here is an individual.
- 22:10And there's a wide variety of
- 22:13how this a few each charm.
- 22:16Have gained weight, right?
- 22:18What the heck?
- 22:20He started these medicines.
- 22:22And they didn't.
- 22:23They might have gained a little bit on them.
- 22:26And in obesity medicine,
- 22:28we're unfortunately at a place where
- 22:30there's we're still a little bit.
- 22:33Um, at a trial and error we can
- 22:35say these are the averages,
- 22:37but you can't really tell how
- 22:39well any individual therapy will
- 22:41work for an for that the patient
- 22:44that's sitting in front of you.
- 22:47The goal here?
- 22:49The Holy Grail.
- 22:50Is to be able to maybe phenotype
- 22:53obesity and and target those
- 22:55patients are correctly all right,
- 22:58but we're just not there yet.
- 23:02So. You know, someone comes in,
- 23:06they lost £10, you know, they weigh maybe
- 23:10£200 and they they're kind
- 23:11of down on themselves and
- 23:13they don't,
- 23:13they didn't lose much weight well.
- 23:16Even small changes in weight
- 23:18are important for your health.
- 23:20So even a 5% change in your weight
- 23:24will affect diabetes, cholesterol,
- 23:27hypertension, steatosis.
- 23:31And no PCOS and hypogonadism.
- 23:35So these these quote UN quote small
- 23:39changes in weight really do have important
- 23:43impacts and and should be followed.
- 23:47So even if even if it doesn't seem like
- 23:49a really big weight loss, all right.
- 23:53For obstructive sleep apnea specifically.
- 23:58Usually in here we're seeing set 7 to 11.
- 24:01I usually say if someone's
- 24:04lost 10% of their body weight.
- 24:07Maybe we can think about retesting them.
- 24:10OK, so. Fine.
- 24:12We've been talking a lot.
- 24:15Weight loss and on the, you know,
- 24:18understanding it as a disease,
- 24:20how does that affect, you know,
- 24:23sleep as a field? Well,
- 24:26weight loss has a significant effect on OSA.
- 24:29This is one of many studies.
- 24:31This was an RCT.
- 24:34Uh,
- 24:34that was 89 patients that were
- 24:36randomized to CPAC or CPAP plus
- 24:39of weight loss intervention and
- 24:41that was defined as nutrition
- 24:43plus an alcohol intervention
- 24:45plus tobacco plus exercise.
- 24:47This was 100% Hispanic population.
- 24:50middle-aged men that you know
- 24:52they were recruiting 18 to 65
- 24:54is mostly patients in their 50s.
- 24:58There there are some caveats
- 25:00to this study in general.
- 25:02Specifically, the alcohol cessation
- 25:04has effects on apnea as well,
- 25:07and they didn't really talk
- 25:09about obesogenic drugs,
- 25:09but without getting too far into the weeds.
- 25:13They found that, you know,
- 25:14weight loss had a significant
- 25:17effect on on sleep apnea.
- 25:20And and so when we and.
- 25:22Sorry for this.
- 25:26Picture is more significant decreases in age,
- 25:29I mean patients lost like 7 kilos so,
- 25:33so pretty substantial weight loss,
- 25:36so £1415 each and then.
- 25:41But they had significant
- 25:43improvements in their oxygenation.
- 25:46You know, mean SP O2, total sleep time,
- 25:49sleep efficiency, sleep latency.
- 25:54Wake after sleep onset there was
- 25:56a decrease in N1N2 and an increase
- 25:58in N3 and an improvement in all
- 26:01eight type of RAM and non R.E.M
- 26:04and and really what was most striking
- 26:08is of of these you know kind of treated
- 26:13population that when they looked at them
- 26:16again after the weight loss 10 out of
- 26:18this on 10 out of the the I think it was
- 26:2134 that made it to the end of the trial.
- 26:24We're in complete remission meaning an age
- 26:26high less than five which was quite exciting.
- 26:30So perhaps with weight loss in the
- 26:32right population this would be a a
- 26:35reasonable adjunct therapy and and
- 26:37might there might be a reason to
- 26:40repeat a study in these patients. Umm.
- 26:44Just kind of harping on the same idea,
- 26:46this specification of many studies looking
- 26:49at the effect of OSA, I'm sorry,
- 26:51effective weight loss on OSA,
- 26:53we can kind of predict a
- 26:56reduction with weight loss,
- 26:59but I think this works better
- 27:01in populations rather than
- 27:05individuals on security summit.
- 27:08Questions. Oops.
- 27:12Lost my mouse. Sorry.
- 27:23Sorry, I lost my mouse.
- 27:262 seconds technical difficulties.
- 27:28Can I? Can I have the questions
- 27:30right out to me? Because I can't.
- 27:32I can't seem to get to them.
- 27:36There's no question yet, Brian.
- 27:38OK. This is just OK. Sorry, no worries.
- 27:58OK. All right.
- 28:05Alright, so sleep disorders and diabetes,
- 28:09this was, you know, I used this,
- 28:12this was this picture is from a review I use.
- 28:14I'm going to use it kind of
- 28:15as a framework to think about.
- 28:19Diabetes and sleep on the the big
- 28:21picture is that sleep fragmentation
- 28:24and disruption by really any
- 28:26mechanism raises sympathetic Dr.
- 28:28and it's thought to worsen glycemic control.
- 28:31And sleep deprivation,
- 28:32you know result in a pro inflammatory
- 28:35stage and and could result in
- 28:37hyperglycemia for that reason, so.
- 28:41This, this kind of review looked at
- 28:45different both circadian disruption
- 28:46and insomnia and they they kind
- 28:49of poorly defined insomnia.
- 28:51So it really was insomnia for any reason.
- 28:55But, but the consistent findings
- 28:57are really that you're the patients
- 28:59who were had reported insomnia or
- 29:01were shift workers or had some
- 29:03sort of circadian disruption had
- 29:05worsening in their A1C's?
- 29:08I don't really like their
- 29:10description of insomnia,
- 29:11so I I would mostly say that
- 29:13sure if you have sleep disruption
- 29:15you'll have likely have worsening
- 29:18of complications from diabetes,
- 29:19but I I think.
- 29:22If you have if it's just primary insomnia,
- 29:25maybe less so than if it were because of OSA,
- 29:28etcetera.
- 29:29There has been an association
- 29:31with you know worsening mental
- 29:33status and perhaps neuropathy
- 29:36with with circadian disruption.
- 29:37I don't think we have a good answer
- 29:41on macrovascular complications,
- 29:42but but certainly we know that there's a
- 29:45metabolic effect of circadian disruption.
- 29:50And then? In terms of OSA,
- 29:53there have been several studies
- 29:55that looked at, you know,
- 29:57on diabetes and OSA and whether it's
- 30:00because it's through you know directed
- 30:03directly affecting glycemia or if it is
- 30:07a risk factor for for other issues that
- 30:09can can that are associated with diabetes.
- 30:13I think it is is debated.
- 30:15But there have been associations with
- 30:18an increase in your A1C retinopathy.
- 30:21There's been some increase
- 30:23with chronic kidney disease,
- 30:24neuropathy and macrovascular complications.
- 30:29And that recurrent, you know,
- 30:30airway obstruction is thought to.
- 30:35It is thought to cause the the.
- 30:41It's thought to cause intermittent hypoxia,
- 30:44and that hypoxia can drive things like
- 30:47increasing both increased insulin resistance,
- 30:50increased beta cell apoptosis and animal
- 30:53models increased hepatic glycogen.
- 30:55There's a few, basically a few mechanisms.
- 30:57I'll I'll give a shout out
- 30:59to to Doctor Andre Zinchuk,
- 31:02who's done some work on this with
- 31:05me and found that there was an
- 31:08association with Hypopnea and hypoxia.
- 31:10Um, that was associated with
- 31:13incident diabetes.
- 31:13We also found in another review
- 31:16of the dream cohort that and
- 31:18this was also with Doctor Yagi.
- 31:23That you know more that maybe
- 31:27hypoxia was more associated.
- 31:30With instant diabetes and pre diabetes,
- 31:33so, so maybe there is more of
- 31:35an effect from that hypoxia,
- 31:37but I think that's still hotly debated.
- 31:42This was a study by this was our
- 31:45review of the, you know, sleep heart,
- 31:47Sleep Heart Health study that was
- 31:49looking at fasting blood sugars and Homa
- 31:52IR in patients with higher RDIS and
- 31:54the Homa IR was basically elevated and
- 31:57so and for those who are unfamiliar,
- 31:59it's the Homa IR is a.
- 32:04Is a measure of insulin resistance,
- 32:06which is the fasting insulin
- 32:08times the fasting glucose over
- 32:10405 and you get a score and you
- 32:13can determine insulin resistance.
- 32:14And this was, you know,
- 32:16one of the earlier studies that
- 32:18have shown there is, you know,
- 32:20some some increase in insulin resistance
- 32:22and I think there's a lot of data on this.
- 32:26Off hand I'll say that the the
- 32:29data that I know patients might
- 32:31have an increase of .5 in their
- 32:34A1C but but I think still not,
- 32:39not a massive increase.
- 32:43And then diabetes and restless
- 32:45legs that the biggest thing is
- 32:48kind of concomitant things that
- 32:51might happen with restless legs.
- 32:53The things I think of aren't usually
- 32:56the macrovascular complications.
- 32:57There has been an increased
- 33:00association of neuropathy and RLS.
- 33:02So so in in the literature depends
- 33:05on where you read it can be
- 33:07anywhere from 55 to 5050% increase
- 33:10in in a in these diseases.
- 33:12I'm not sure if people are looking at
- 33:14the same time but it has been associated
- 33:17and the important piece of this too is
- 33:19that patients with.
- 33:24You know neuropathy and unless
- 33:25you might have an overlap syndrome
- 33:27and you they might be hard to
- 33:29distinguish which which they
- 33:31are unique diseases, but
- 33:33it might be hard to distinguish
- 33:34which one is causing the problems.
- 33:38Can cause sleep disruption.
- 33:41Alright, so how do we approach these
- 33:45patients and and what how should we
- 33:49treat obesity well weight loss goal
- 33:52and I this is a you can talk about
- 33:55a weight loss goal with patients.
- 33:57With the idea that.
- 34:00You might need to tailor therapy.
- 34:02Certain certain medicines will not achieve,
- 34:05you know, a weight loss goal.
- 34:07Or patients might say I want to be
- 34:09half my weight and you might say boy,
- 34:11medicine is just not going
- 34:12to accomplish that.
- 34:13You might need to go to surgery.
- 34:16Uh, what their peak weight was.
- 34:18Because that might tell you where really
- 34:20that that's part of the weight history.
- 34:22And the reason the weight history is
- 34:24important is that tells you where
- 34:26the set point has become has changed
- 34:28over the years and how it has,
- 34:30how it has gone, triggers.
- 34:32And really, you know,
- 34:33kind of that goes hand in hand
- 34:35with the psychiatric history,
- 34:37looking for history of anorexia,
- 34:39binge eating, things like that,
- 34:41because those things need
- 34:42to be treated differently.
- 34:44Obviously a sleep history for
- 34:46the reasons I just described.
- 34:48A history of alcohol,
- 34:49drug use, family history,
- 34:51so for for cardiometabolic.
- 34:54Issues and then evaluation of medicines.
- 34:58Well, we'll take a quick look at
- 35:00what obesogenic medicines might.
- 35:02An evaluation of other
- 35:03syndromes, namely I always look at cushings.
- 35:08Thyroid disease and monogenic
- 35:10obesity is a rare finding.
- 35:12But we should always, you know,
- 35:14if someone has started gaining weight before
- 35:16age 5 and they have some unusual findings
- 35:18and they're quite heavy at a very young age,
- 35:21we we should think about that as as
- 35:24a as something to chase. All right.
- 35:27So what causes weight gain?
- 35:30Lots of stuff.
- 35:31And I won't go through all of these.
- 35:33I'll highlight a few of these.
- 35:35This is recorded.
- 35:35So if someone wants to kind of go
- 35:37through each of these, that's fine, died.
- 35:39The ones I always think of in diabetes is
- 35:42insulin and sulfonylureas TZD's do too.
- 35:46But patients are often on these medicines
- 35:50and and you know switching them over
- 35:52to more weight neutral or weight,
- 35:54weight negative agents.
- 35:57Is you know kind of what I would
- 35:59say standard of care nowadays.
- 36:01Simple things that others everyone's
- 36:03on metoprolol.
- 36:04How many patients are on metoprolol?
- 36:06It's weight promoting and if if that
- 36:08patient can be changed to his CB rate right,
- 36:12that might be more of a weight neutral agent.
- 36:16The same goes with antidepressants
- 36:18and the the best one that you know,
- 36:20bupropion is the best choice from
- 36:22my standpoint just because it has a
- 36:25little bit of a weight negative effect,
- 36:26whereas sertraline and fluoxetine
- 36:28are just a little bit weight neutral.
- 36:31But there's a lot of different things
- 36:33and obviously what comes first is you know,
- 36:35the patient needs to have good
- 36:38control of their blood pressure or
- 36:40their mental health and all these
- 36:42other things work around this.
- 36:43But these are simple things that
- 36:45we might be able to change that.
- 36:46Might affect wait.
- 36:50All right. So let's talk about
- 36:54the medicines that are most
- 36:57commonly used and and are kind
- 37:00of the exciting medicines which
- 37:01are GLP one receptor agonists.
- 37:03The most common one used nowadays
- 37:05is something called semaglutide.
- 37:07It's also known as ozempic or we govy.
- 37:11This is also in the class of the new
- 37:13drug called terza Appetite, but we'll
- 37:15we'll have a separate slide on that.
- 37:18The big picture is, is that?
- 37:20GLP one receptor agonists
- 37:22work in the nucleus accumbens,
- 37:24decreasing the reward pathway in the
- 37:27hypothalamus and that improves your satiety.
- 37:29It also slows down gastric emptying and
- 37:31gives you some increased stomach stretch.
- 37:33But that's the mechanism, right?
- 37:35So it it it affects growing
- 37:38at the stomach and.
- 37:39Also has a direct effect on the brain.
- 37:43So how do we start these meds again,
- 37:46not going to go into the nitty gritty here.
- 37:48Usually you start at a low dose.
- 37:51I I titrate slowly increasing only at 4
- 37:56weeks and then common common issues that
- 37:59everyone should be counseled on nausea.
- 38:02If someone is vomiting,
- 38:03the dose needs to be decreased.
- 38:06Some patients do have some Constipation,
- 38:08they can have an increased heart rate.
- 38:10In study it's only like 2
- 38:11to 3 beats per minute,
- 38:12but that does happen sometimes.
- 38:16Usually not an issue, usually
- 38:18not a concern for someone with
- 38:20arrhythmia. That's more of a
- 38:22a issue with phentermine than these.
- 38:24And then the scary things are pancreatitis,
- 38:28acute gallbladder disease,
- 38:31gastroparesis and then if someone's
- 38:33pregnant they can't be on this.
- 38:35And then there has been mixed
- 38:38studies on medullary thyroid cancer.
- 38:40These were this was really from
- 38:42animal studies with Victoza. That
- 38:44there was an increased risk in rats.
- 38:46There's a recent French study that was
- 38:48poorly done that said that there was
- 38:51an increase of all thyroid cancers,
- 38:53including medullary thyroid cancer.
- 38:56I won't go into the the details.
- 38:57I'm a little bit skeptical of that study.
- 38:59I don't think that that Hillary thyroid
- 39:02cancer as a cancer is exquisitely
- 39:04rare and I don't know that this
- 39:06is is is really significant risk,
- 39:09but patients should be made aware
- 39:11of the data. Umm. Alright, so.
- 39:15Tricep atide, right.
- 39:17So we, we we looked at these numbers
- 39:20briefly 15 to 17% average weight loss and
- 39:24we remember average weight loss, right.
- 39:27So we have this long.
- 39:29We have this waterfall plot
- 39:31that's associated with this,
- 39:32but average is 15 to 17% at Max
- 39:35dose after really 18 months or so.
- 39:38And tricep petite at Max dose,
- 39:40which is our new agent, it's 22.5%,
- 39:43which is massive.
- 39:45That's crazy because when we look
- 39:48at a gastric sleeve surgery,
- 39:50it's closer to 25 to 30%.
- 39:55So we're approaching those levels.
- 39:56So you had patients that had us in that
- 40:00study that had 37% of their total body
- 40:03weight off on Max dose tres appetite.
- 40:07So what's the difference
- 40:09between perception Jaro versus?
- 40:13Versus semaglutide.
- 40:15Well, it's a dual agent 2 hormones,
- 40:18it's GLP one. And G&GIP, right.
- 40:20So this is what the new new age
- 40:22is and that's what people are are
- 40:24doing is they're going to be start
- 40:27combining hormones in these new agents.
- 40:30So let's apply that how does
- 40:33weight loss look in a case?
- 40:35So this is a patient actually saw a
- 40:38while ago so the the drugs are not
- 40:40are so it's before summer was out
- 40:43or was just coming out as patient
- 40:46was a 53 year old class three class
- 40:49I'm sorry Class 3 obesity this is
- 40:52that's that's this type BMI 48 Type
- 40:562 diabetes thyroid nodules anxiety
- 40:58unless Lexapro who presents for weight
- 41:01management was overweight as a child
- 41:04after age 5. Peak weight was 283.
- 41:07Her goal weight is 200.
- 41:09What can be done? Well,
- 41:12this is her weight graph over the years.
- 41:14So she was initially on metformin and lira
- 41:17and that was titrated up and she was at 2 at,
- 41:20you know, in the two 80s and
- 41:22then didn't tolerate metformin.
- 41:23So she was decreased.
- 41:25She stopped off Metformin and
- 41:26Lyra was increased.
- 41:28So she went down all the way to,
- 41:30you know, 245.
- 41:32And then she started herself on metformin,
- 41:35and we they we increased
- 41:37her on lira some more.
- 41:40And she was down to two, you know,
- 41:42235 stabilized there, she started on.
- 41:46Naltrexone be propriano Contrave.
- 41:49Which was increased.
- 41:52But she didn't tolerate it very well,
- 41:54so she was only so she stopped.
- 41:56She had headaches, flushing abdominal pain.
- 41:59That was stopped.
- 42:00She started on Topiramate
- 42:02responded pretty well.
- 42:03And they get and then started on,
- 42:05you know, a little bit of phentermine.
- 42:08And she's down to £200 or abouts there,
- 42:12little bit above right?
- 42:13And this might be more of a.
- 42:18And I think with some of the new
- 42:20drugs you'll you'll see some.
- 42:21More impressive effects for any
- 42:23specific drug, although she did
- 42:25respond really well to lira.
- 42:28But this is kind of what you can expect
- 42:29is this is going to be a push pull.
- 42:31Some drugs won't work for the patient,
- 42:33there will be side effects.
- 42:34So I I've kept this slide intact
- 42:36to say that it's not, you know,
- 42:38none of these are a magic pill,
- 42:40but you have to kind of feel it
- 42:42out and see which which medicine
- 42:44works and what doesn't and what's
- 42:46side effects are tolerable or
- 42:49inappropriate for any given case.
- 42:51All right. So what's next?
- 42:53What's on the horizon?
- 42:54A whole bunch of agents,
- 42:56amylin, GLP, Glucagon, GLP.
- 42:58So Glucagon has a little bit of a.
- 43:03Energy effects, I'm sorry,
- 43:04uh, energy expenditure effect.
- 43:05So we'll see how that works in people.
- 43:07That's in mouse studies right now.
- 43:10And then there is a trial of
- 43:12Tracepath tide on sleep apnea,
- 43:15which is kind of exciting because they're,
- 43:17you know, if it comes positive,
- 43:19which I suspect it will,
- 43:21maybe there will be an indication
- 43:23for sleep apnea for these drugs,
- 43:25which would change how we start managing
- 43:27how we manage some of these cases.
- 43:31All right, so.
- 43:33To conclude, obesity is a complicated,
- 43:37multifactorial disease process
- 43:38that is prevalent and undertreated.
- 43:41Obesity, sleep and diabetes
- 43:43are profoundly interrelated.
- 43:45A treatment of obesity should focus
- 43:47on the adjustment of that weight,
- 43:49the weight set point right?
- 43:51And that can be done through
- 43:53multiple mechanisms,
- 43:54both conservative and medical.
- 43:55And treating obesity should be
- 43:57done with a team based approach.
- 43:59So nutritionists, you know.
- 44:03Psychiatry, sleep, medicine, GI, surgery,
- 44:06everyone is involved in these cases.
- 44:08So it's not one one person
- 44:10that's managing everything.
- 44:11We really get everyone on board and
- 44:14and then all of this, you know,
- 44:16we haven't gone through all the medicines,
- 44:18but a lot of this is figuring out
- 44:20what is the right fit for a patient.
- 44:22So medicines should be medicines and other
- 44:25therapies need to be approached through
- 44:26a shared decision making process.
- 44:29And treatments of obesity for obesity
- 44:31should be evaluated as a potential
- 44:33option for patients with OSA because it,
- 44:36you know, we we have.
- 44:38We have studies showing that weight
- 44:42significantly affects OSA and sleep
- 44:45quality and now we have medicines that
- 44:48significantly affect weight that maybe we
- 44:51should be using some of these therapies
- 44:54in concert with CPAP and then seeing if
- 44:58patients potentially can get off PAP,
- 45:00you know, in time.
- 45:01But I would say that's going to be
- 45:04probably a smaller percentage of patients.
- 45:06We're always hopeful,
- 45:07but we we should always be keeping that.
- 45:11All right, questions.
- 45:13Great.
- 45:14Thank you so much, Doctor Roger,
- 45:16for this extremely educational talk,
- 45:19excellent talk.
- 45:21So if you have any questions,
- 45:24feel free to unmute yourself and ask.
- 45:26And I do have one question
- 45:27in the chat room for you.
- 45:29What is monogenic versus polygenic?
- 45:32Sure, great question.
- 45:37Specific gene associated with it.
- 45:40So the examples I think of are specific
- 45:43mutations on MC4R mutation, TOMCC mutation.
- 45:47The reason it's important to make that
- 45:51distinction so polygenic is probably.
- 45:54Most patients have right or or plain old
- 45:58obesity that is we we don't have a specific
- 46:02gene to monogenic obesity usually has
- 46:04and other syndrome associated with it.
- 46:07So for instance a pomsky mutation
- 46:10will often present with adrenal
- 46:12insufficiency right because there's
- 46:15there's another gene issue with it.
- 46:17The other way you know common ones
- 46:19that you might think of are leptin
- 46:21deficient leptin receptor deficiencies.
- 46:23It does have a have a certain
- 46:27presentation many monogenic
- 46:29obesity presentations will have.
- 46:32So they're syndromic is is
- 46:33what I'm really trying to say.
- 46:35And the the reason it's there are two
- 46:37reasons it's important to find them.
- 46:38Sometimes because there's syndromic,
- 46:40they have another endocrine issue associated
- 46:43that you need to treat and find.
- 46:45And then the other piece is they
- 46:47might be a candidate for drugs
- 46:49that are more effective, all right.
- 46:52So if someone has a leptin receptor
- 46:55deficiency, they their candidate to
- 46:58be treated with MC4R or set millana
- 47:02tide and those patients usually
- 47:04are heavier and they'll have,
- 47:07you know I have a patient that I've
- 47:10had patients that are quite heavy.
- 47:13And they they can be treated with.
- 47:16That sent Melanated an average.
- 47:18You know we're talking 22.5
- 47:21at with tricep petite.
- 47:23Set melanotic can get like a 30% response.
- 47:26So, so much more impressive for
- 47:29the for that specific population.
- 47:32Is is that helpful?
- 47:38OK, I have. Uh-huh.
- 47:41I have a question about non
- 47:45pharmacologic approaches that
- 47:46there appears to be 2 popular.
- 47:50Opposing views.
- 47:52One is the benefit of frequent small.
- 47:58Meals, particularly with
- 48:00a lot of protein snacking.
- 48:03And the other is the approach of of of
- 48:08long periods of fasting between eating.
- 48:12Do you have any strong feeling
- 48:14based on your experience?
- 48:16So there's data on this,
- 48:19yes so as far so.
- 48:24The the biggest picture is I'm still
- 48:27going to stick with the idea of.
- 48:28Reducing reducing calories but
- 48:31maintaining satiety and so however
- 48:35someone accomplishes that great and
- 48:39you are obviously tailor diets to to
- 48:43someones comorbidities Mediterranean
- 48:44diet more for cardiovascular,
- 48:46dash or hypertension.
- 48:47But that's not your question right.
- 48:50Your question is does does
- 48:52intermittent fasting work and the
- 48:54answer is there was a recent study
- 48:56that mostly said no not really.
- 48:58Uh, but I think that doesn't mean
- 49:00that I haven't had patients that said,
- 49:02boy, I've done this intermittent
- 49:04fasting thing and it works.
- 49:06What about protein?
- 49:07What about composition protein?
- 49:09So what makes you feel full?
- 49:12Things that make you feel full
- 49:14are one protein, followed by fat,
- 49:17followed by carbs, right?
- 49:19So those things make you feel full
- 49:22and have a pretty good calorie
- 49:24density if if their health, you know,
- 49:27healthy if you have a good.
- 49:30If you have like steak that's not
- 49:33particularly like a lean meat,
- 49:34it will make you feel full at
- 49:36a lower calorie density.
- 49:37So I don't have anything,
- 49:39I don't have any problems with
- 49:42people choosing a protein,
- 49:44heavy or not heavy, but a protein,
- 49:48vegetable, vegetable based diet.
- 49:49And I'm more of a diabetologist, right?
- 49:52So if you're not eating carbs I'm
- 49:55happy but but but I don't have a
- 49:58problem with that diet per se.
- 50:00The, the.
- 50:00What I find is that there's some
- 50:03things that people cannot adhere to,
- 50:05and I think the the biggest thing
- 50:07is finding the right thing that
- 50:09someone can adhere to with with
- 50:12that thoughtful idea of choosing,
- 50:15choosing specific things that make
- 50:17you feel full at a lower calorie density.
- 50:19So I have no problem with that.
- 50:21So short answer is.
- 50:26From what I've seen,
- 50:27the data does not really support
- 50:30intermittent fasting very well.
- 50:32I've had anecdotally a few
- 50:34patients that do well with it.
- 50:36Great. As far as composition,
- 50:41having a higher protein with with a little
- 50:46bit of with with veg based diet is fine.
- 50:49It will make you feel full at probably
- 50:52a lower calorie density and at but won't
- 50:56fix the fix the underlying problem.
- 50:59Is that helpful?
- 51:01And one other question is,
- 51:02is it is it a serious problem of people
- 51:07eating at night in combination with with the?
- 51:13With, well, just the evening snacking
- 51:18and and the problems with melatonin,
- 51:24I haven't seen a lot of that.
- 51:25I have, I have.
- 51:29I have had patients that
- 51:30do the evening snacking,
- 51:32but that's usually because they're
- 51:33busy during the day and then they eat
- 51:35nothing and then they binge at night.
- 51:37But I haven't seen that specific
- 51:39association with melatonin,
- 51:40or at least not consistently.
- 51:45Thanks, Brian. Another question I have
- 51:47from Doctor Ruth and a comment, great.
- 51:50Doctor Brian, would you prescribe trouser
- 51:52petite for a limited period of time
- 51:54only in patients who have multinodular
- 51:56goiter or avoid these medications?
- 52:00Question. Um, so my thyroid colleagues
- 52:02send those patients straight to me.
- 52:04They've had cancer.
- 52:06So as long as they're not
- 52:08medullary thyroid cancer and they
- 52:10don't have that specific cancer.
- 52:13We still prescribe it. So.
- 52:15So yeah, that's if and in fact obesity.
- 52:20It's been shown to reduce incidence
- 52:23of papillary thyroid cancer,
- 52:25which is far more common, right.
- 52:27So it's one of the 13 cancers
- 52:30that's been associated.
- 52:31So, so sorry,
- 52:32obesity has been shown to increase that.
- 52:34I think I said that right.
- 52:35So treating obesity should actually improve
- 52:38thyroid cancer or most thyroid cancers,
- 52:41but it will not it,
- 52:43but treating with a GLP or GLP one Giphy
- 52:47agent may would be contraindicated.
- 52:50Than someone with a history,
- 52:52family history or personal history
- 52:54of medullary thyroid cancer.
- 52:58Thank you. Another question,
- 52:59are there any R cities
- 53:01about combined treatments
- 53:03medication with psychotherapy?
- 53:04Is the combination better
- 53:06than just one approach?
- 53:08So almost all, almost all studies consider
- 53:13conservative management as baseline.
- 53:16So what conservative management
- 53:18to me is nutrition often like
- 53:21consistent nutritional visits,
- 53:24you know some some sort of
- 53:26psych something you know?
- 53:28It's usually more of a nutrition based thing.
- 53:30Generally speaking,
- 53:31the medicines are more effective for
- 53:33any for an individual on average.
- 53:36But I think there are
- 53:38several important caveats.
- 53:39Binge eating disorder is one
- 53:41of the biggest ones, right?
- 53:42So people who have binge
- 53:45eating disorder need to be.
- 53:49With the with with a good
- 53:52psych team because all
- 53:53the drugs ever do is improve
- 53:56is change the fat mass setpoint
- 53:58people who binge eat past satiety.
- 54:01So I can't fix that.
- 54:04That needs a different,
- 54:05that needs a different therapy
- 54:07and that can be done with.
- 54:09So the medicine that's sometimes
- 54:10used for it is Vyvanse.
- 54:11I don't prescribe it because it's a psych
- 54:14indication or I don't usually prescribe it.
- 54:17But also there there needs to be a
- 54:19good good psych support with that.
- 54:20So I I think that the the studies
- 54:23have some sort of support maybe
- 54:25less psych support in other in
- 54:28other cases and I think the biggest
- 54:30caveat is in patients that binge.
- 54:33So most of the time the medicines.
- 54:38But it's it's really.
- 54:39You should be treating everything.
- 54:41You should be treated everything.
- 54:44OK. What's wrong? We have a
- 54:49question from Doctor Hoffman.
- 54:50Have you had any success with evening
- 54:52overnight fasting of 12 hour or more?
- 54:57I have, like I said, you know,
- 54:59anecdotally I've had,
- 55:01I have maybe one or two cases that
- 55:03do intermittent fasting and say,
- 55:05boy, this is really working for me
- 55:07and that's great, that's fantastic.
- 55:10Maybe they have a specific
- 55:12phenotype that, that, that.
- 55:15And so, So what often happens
- 55:18with intermittent fasting is people catch
- 55:22up during the the non fast time.
- 55:24On this far as their calorie
- 55:26intake but some people respond
- 55:29well to the to that time restricted eating.
- 55:31So I would say yes sometimes and I don't
- 55:36necessarily see anything wrong with with
- 55:38that if that works for a specific patient.
- 55:43It's David. And do you have any
- 55:46data on the wakefulness promoting
- 55:48benefits of the fasting state?
- 55:51Not necessarily for something
- 55:53that would be, you know,
- 55:55drive you down the path of weight loss,
- 55:57but maybe serve the weight promoting thing.
- 55:59Because I do know that being
- 56:02vigilant seems to be a side effect
- 56:04of being in the fasting state.
- 56:05There is some data out there,
- 56:06but I'm not too familiar with it.
- 56:08I was wondering whether
- 56:09you knew anything about it.
- 56:11I think it's hotly debated.
- 56:15I, I, I, I, you know, and there's.
- 56:18I think being in like the ketosis
- 56:21has been argued to maybe make
- 56:23you feel a little bit more,
- 56:26not like there's nausea associated
- 56:28with being ketotic, right?
- 56:30And the thought is that maybe
- 56:32if you're a little ketotic.
- 56:34You
- 56:34will have a little bit of
- 56:36nausea and maybe that will
- 56:39and that's what you're trying to accomplish
- 56:40and to some degree through fasting, right?
- 56:42It's not just that you didn't eat
- 56:44enough carbs, it's boiled, you know,
- 56:45it's this is another way to maybe
- 56:47achieve a little bit of ketosis.
- 56:50And so, so I I think.
- 56:53That is a hotly debated topic.
- 56:56I haven't been convinced that.
- 56:59Achieving ketosis through fasting
- 57:01or otherwise is is very weight
- 57:04promoting or particularly helpful?
- 57:07Umm, you know,
- 57:09certainly you can lose a lot of
- 57:12weight quickly if you eat very very
- 57:14little and on an architonic, but.
- 57:17Long term,
- 57:19I suspect you will regain it based on,
- 57:21you know understand that
- 57:22the the disease process.
- 57:27Period. Is that help?
- 57:30You're going back to that patient,
- 57:33you showed that loss from 280 to
- 57:35200 on various medications if.
- 57:39Now that the patient has reached 200,
- 57:41if you stopped all those medications,
- 57:44what would you predict would happen?
- 57:45And those, have you changed the Physiology
- 57:48of that patient in any way being at
- 57:51200 rather than 280, if you could?
- 57:53Great, great, great question. Sorry,
- 57:54I didn't make a punctuated point about this.
- 57:57It's very important.
- 58:00Regain the weight, right? Absolutely.
- 58:03So we have not cured obesity.
- 58:06Um, you have treated it and that's true of
- 58:11surgery, that's true of medicine, right?
- 58:13So if if I take a patient that is BMI 50,
- 58:17take them to the OR and change
- 58:20their Physiology, right,
- 58:21because it's a metabolic surgery,
- 58:23it affects hormones that it's
- 58:25not just malabsorptive.
- 58:2710 years down the line,
- 58:28they might regain that weight and we've
- 58:30seen those cases plenty of the time, right?
- 58:32Is that a 10 years, hey,
- 58:33this bariatric surgery didn't work.
- 58:34No, their disease has progressed,
- 58:36right and that is a fix to
- 58:38the fat mass set point.
- 58:39But disease progresses now with
- 58:41medicines we've tried, right?
- 58:43So there's a great study
- 58:45with phentermine topiramate,
- 58:46which was a crossover and they
- 58:48looked and said, can we stop it?
- 58:51Because no one wants to stay on medicine
- 58:53forever. And the answer was no.
- 58:55They they had, you know,
- 58:57just a lifestyle quote,
- 58:58UN quote lifestyle intervention and then
- 59:01lifestyle plus phentermine topiramate
- 59:03halfway through you could quit.
- 59:05And they rejoined their colleagues
- 59:07at the lifestyle.
- 59:08So it really kind of gave you that show,
- 59:10that boy,
- 59:11there is that fat mass set point
- 59:13because they went back to where
- 59:14we would expect them to go.
- 59:16So yeah,
- 59:17I'd expect that patient to regain
- 59:18all that weight, that being said.
- 59:22I'll give you the caveat of
- 59:24a super responder, right,
- 59:25because I gave you an average case.
- 59:27I had a case that was in the 400 about
- 59:31little over £400 when they saw me on insulin.
- 59:36For diabetes on statins.
- 59:39Required knee surgery for osteoarthritis.
- 59:43Could not get it because
- 59:45of the weight requirement.
- 59:46Terrible OSA, etcetera, etcetera, etcetera.
- 59:48Started them on some meglitinide.
- 59:511 milligram, not full dose, right?
- 59:53So I got them to 1 milligram after
- 59:55three months they lost touch with me,
- 59:57but I saw them in a year lost
- 59:59£120.00 off insulin, off statin,
- 01:00:03off blood pressure pills,
- 01:00:05got their surgery, can walk now.
- 01:00:08So like it, it really depends, right?
- 01:00:11You can have really profound effects
- 01:00:14and that's not an average case
- 01:00:15is is you can have rip but you
- 01:00:18can have really profound effects
- 01:00:20with these medicines that are.
- 01:00:22Really life changing.
- 01:00:23The problem is that I don't know
- 01:00:25the next guy might give the same
- 01:00:27medicine and it's you got a £5
- 01:00:29weight loss and what in this is that
- 01:00:32worth it right and and so and so
- 01:00:34it's a constant reevaluation of are
- 01:00:37these medicines effective for you.
- 01:00:39What other medicines can we peel
- 01:00:41off because once you start these
- 01:00:43medicines my next job is to say can
- 01:00:45we stop the blood pressure pill
- 01:00:46can we stop the cholesterol pill?
- 01:00:48What what can we start peeling off
- 01:00:50so it's a it's I follow patients.
- 01:00:52Three to four months and and
- 01:00:54reevaluate pretty regularly.
- 01:00:59Thanks. Yep. Thanks a lot, Brian. We
- 01:01:04have one comment from Doctor Radaker.
- 01:01:06Nice talk, Ryan.
- 01:01:07Great to see everyone.
- 01:01:10Thanks if anyone has any questions.
- 01:01:15If not, thank you so much again.
- 01:01:17It was a terrific talk.
- 01:01:19More patience coming your way.
- 01:01:21Alright, bye everyone.
- 01:01:24Enjoy your vacation.