Sleep 2023.02.22 Wojeck

March 11, 2023

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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&amp;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.