The Yale Legacy Collaborative

Transcript

• 00:00Hi. My name is Claire
• 00:02Flannery.
• 00:03I'm an endocrinologist
• 00:05and a researcher in women's
• 00:06health,
• 00:08diabetes and body weight here
• 00:10at the Yale School of
• 00:11Medicine.
• 00:12And, today, I'm very excited,
• 00:15to have a conversation with
• 00:16Doctor. Sonia Caprio,
• 00:18who is also an endocrinologist
• 00:20here at Yale and who
• 00:21studies,
• 00:22how body weight and diabetes
• 00:25evolves in,
• 00:26children and teenagers.
• 00:29I've long admired her work,
• 00:30and so this is a
• 00:31privilege to get to speak
• 00:32with her. I also we
• 00:34have recently joined forces,
• 00:37so to understand how these,
• 00:39children and teenagers have now
• 00:41grown up as adults and
• 00:42how they're doing.
• 00:45Thank you very much for
• 00:46inviting me. And,
• 00:48yes,
• 00:49the interest is is there
• 00:51for,
• 00:53particularly to start as as
• 00:55the focus was in in
• 00:56diabetes. And slowly, we, understood
• 00:59that there was a link
• 01:01between type two diabetes and
• 01:03and, and obesity.
• 01:05My, interest was mainly in
• 01:07children
• 01:08to see if I could,
• 01:10bring whatever I the experience
• 01:12that we have,
• 01:14and had,
• 01:15in in the field of
• 01:17diabetes
• 01:18to,
• 01:19at that time,
• 01:21I I must say this
• 01:22was the beginning of nineteen
• 01:23nineties, things like that, and
• 01:25there was very little,
• 01:27diabetes,
• 01:29if ever
• 01:30type two diabetes
• 01:31in youth.
• 01:34So little by little, we
• 01:35focus more on on the
• 01:37metabolic syndrome to see if
• 01:39kids with
• 01:41obesity
• 01:42were also,
• 01:44having
• 01:45other problems in the in
• 01:47the lipid
• 01:48system, for example, lipid assessment
• 01:51and
• 01:52and and, hypertension.
• 01:55And, and, at that time,
• 01:56there was no fatty liver
• 01:58yet, in, in in the
• 02:00in the air in in
• 02:01the pro as a problem,
• 02:03at least in kids.
• 02:04So little by little,
• 02:07we moved and and understood
• 02:10that the problem many of
• 02:11the problem that we have
• 02:12in overweight
• 02:14and obesity in adults
• 02:16were also seen in the
• 02:18adolescents that I was seeing
• 02:19in a in,
• 02:20in the clinic.
• 02:22Yeah. So your career
• 02:24in service of children and
• 02:26teenagers
• 02:27has now spanned over thirty
• 02:29years with funding from the
• 02:31National Institutes of Health,
• 02:33which is quite prestigious.
• 02:35And I know that you've
• 02:36written over a hundred and
• 02:38fifty
• 02:39peer reviewed publications.
• 02:41You know, many of the,
• 02:43children and teenagers who saw
• 02:45you in clinic participated in
• 02:46these studies.
• 02:47Yeah. In fact, it started,
• 02:50very fast because
• 02:52we started doing these very
• 02:53simple tests that were
• 02:55raising reasonably
• 02:57accepted
• 02:58by a young person, a
• 02:59a a child, basically,
• 03:01because it was from set
• 03:02the age of seven and
• 03:04up.
• 03:05Once we started,
• 03:07to the the idea that
• 03:08we should basically focus whether
• 03:10there was prediabetes
• 03:12in youth with obesity,
• 03:15we started by doing these
• 03:17tests
• 03:18that were
• 03:20fairly well accepted.
• 03:22Not all not all every
• 03:24child will drink that sugary,
• 03:26test, basically.
• 03:28But that was the main
• 03:30point to do it, a
• 03:31test, a simple test, not
• 03:33very invasive,
• 03:35that would allow us to
• 03:36know where, the glucose,
• 03:40the tolerance
• 03:41is basically, if it's altered
• 03:44or not.
• 03:45And,
• 03:46and to repeat that in
• 03:48two years as a follow-up.
• 03:50That's what we started doing.
• 03:52In the meantime,
• 03:53because year was very and
• 03:56is still very,
• 03:58famous for doing imaging
• 04:00of the body.
• 04:02So we were the first
• 04:03one to do really the
• 04:04imaging of adipose tissue in
• 04:06children that were overweight
• 04:08or not.
• 04:09And so we combined the
• 04:11two things and and, we
• 04:13we started doing these tests.
• 04:16And I would say that
• 04:17by the end the beginning
• 04:19of two thousand, we had
• 04:20about two hundred,
• 04:21kids that underwent,
• 04:24the the OGGTT and,
• 04:28the the imaging.
• 04:29And that paper was very
• 04:31important,
• 04:32at least was accepted
• 04:35in the
• 04:36New England Journal of Medicine.
• 04:39And that opened the door
• 04:41to see, to to let
• 04:42people understand, you know, that
• 04:44the the start of obesity
• 04:46of diabetes
• 04:48started very early, type two
• 04:49diabetes, very early in these
• 04:51kids.
• 04:52So that's what,
• 04:54was the first step and
• 04:56was very well important because
• 04:58then the n I NIH
• 05:00decided to do trials
• 05:02in kids with obesity and
• 05:05type two diabetes and see
• 05:06what would be the best
• 05:07way to treat this many
• 05:09these, problem in kids.
• 05:11And why is it important
• 05:14to diagnose children and teenagers?
• 05:16It's very important because the
• 05:17earlier you start it, the
• 05:19the problem I mean, you
• 05:21you know that they have
• 05:22it because it's not like
• 05:24type one diabetes that it
• 05:25it it comes out and
• 05:27you don't,
• 05:29you cannot miss it.
• 05:31Type two diabetes is sometimes
• 05:33pretty silent.
• 05:35So you see that in
• 05:36the silence is it was
• 05:38there. We did not know
• 05:39about it. And by doing
• 05:40the OGTT
• 05:42and the imaging, we realized
• 05:44that there were other issues
• 05:46in in in in these
• 05:47kids.
• 05:48So we started,
• 05:50basically with type two diabetes
• 05:52when when the NIH
• 05:55also was willing
• 05:56to give, you know, propose
• 06:00a study to see what
• 06:01would be the best way
• 06:02to treat type two diabetes
• 06:04in kids
• 06:05with obesity.
• 06:06And and and that was
• 06:08two thousand and two, two
• 06:09thousand and three that we
• 06:10had the first
• 06:12big
• 06:13center, a group of there
• 06:15were thirteen,
• 06:16centers
• 06:17that the NIH
• 06:19selected,
• 06:21and and to do this,
• 06:22study that they wanted to
• 06:24do, basically. And this was
• 06:25the first time, large,
• 06:28study,
• 06:30to understand what is the
• 06:31problem of type two diabetes
• 06:32in such a
• 06:34young population.
• 06:35Now thirty years after you
• 06:37started,
• 06:38there's over
• 06:39twenty five hundred,
• 06:42individuals who took part in
• 06:43these studies. They are now
• 06:45in their twenties, thirties, and
• 06:46forties. And I'm curious what
• 06:49you would want them to
• 06:50know now.
• 06:52And we both know that
• 06:53we we care how they're
• 06:54doing now, which is one
• 06:55of the reasons I've got
• 06:56involved as an adult endocrinologist.
• 06:59But are there things that
• 06:59you would want them to
• 07:00know? Yeah. This is very
• 07:02the continuity of this problem
• 07:04is very important because, unfortunately,
• 07:07up to twenty one, the
• 07:09pediatrician gets out from the
• 07:11so I cannot connect with
• 07:12them anymore.
• 07:14So having a person in
• 07:15the field,
• 07:17endocrinologist
• 07:18and knows and knows metabolism,
• 07:19I think, is important. And
• 07:20if we can and
• 07:22our goal is to reach
• 07:23out to these people particularly
• 07:26in,
• 07:27some aspects of the problem
• 07:29to see if we can
• 07:31see where are they. Are
• 07:32they having problems? And is
• 07:35and some of them have
• 07:35developed type two diabetes
• 07:38and other issues now because,
• 07:40you know,
• 07:41they have their own family,
• 07:42they have, the obesity does
• 07:45not go away,
• 07:47and the type two diabetes
• 07:48as well.
• 07:50So it would be very
• 07:51important to have,
• 07:52based on what we saw
• 07:54when they were adolescent, what's
• 07:56happening now also,
• 07:58and what best how best
• 07:59we can treat them. I
• 08:01would love to know where
• 08:02they're doing,
• 08:03you know, some of them
• 08:04I know because they come
• 08:05they have other younger
• 08:08brothers and sisters that are
• 08:09still in my clinic.
• 08:11But those that have, matured,
• 08:13they have kids, they're on
• 08:15their own.
• 08:16And that's important because also
• 08:18you don't wanna, you know,
• 08:20have this,
• 08:22type two diabetes and go
• 08:23into pregnancy and things like
• 08:25that. It's another very important
• 08:27area that I don't see
• 08:28a lot of work there.
• 08:30So there is a great
• 08:31deal of,
• 08:33research.
• 08:34We are, I think, in
• 08:35a moment in
• 08:37research and in science now
• 08:39to understand that
• 08:41overweight
• 08:42and obesity
• 08:44is there and is not
• 08:45gonna go away. The key
• 08:47issue is why. It's always
• 08:49the weight that has to
• 08:50go down
• 08:51in order to see that,
• 08:52you know, your glucose tolerance
• 08:54is better.
• 08:56The the liver is doing
• 08:57better.
• 08:59And and so that's that
• 09:00would be a major step.
• 09:02And the goal our goal
• 09:04is really to stop
• 09:05the diabetes, type two diabetes
• 09:07in youth because it's a
• 09:08it's a silent disease.
• 09:12And if you don't take
• 09:13good care, you're gonna they're
• 09:15gonna have most likely some
• 09:17issues later on, you know?
• 09:18And I believe also from
• 09:20your work, a side message
• 09:22that comes through is that
• 09:23not all children are equally
• 09:25at risk and we never
• 09:26want to overtreat
• 09:28those who never needed
• 09:29it. Yeah. It it was
• 09:31clearly
• 09:32that it was that the
• 09:33disease of diabetes would start
• 09:36after they had,
• 09:37the early puberty adult puberty.
• 09:40So they were the mean
• 09:41age was thirteen.
• 09:43You seldom
• 09:44was seeing, you know, very
• 09:46early diabetes
• 09:48in pre pubertal kids. It's
• 09:50very rare. But it was
• 09:52there when they were in
• 09:54in adolescence.
• 09:56Prediabetes
• 09:57is very,
• 09:58easy for,
• 10:00for kids, particularly,
• 10:02I would say boys, going
• 10:03back to normal. So we
• 10:04have a paper in in
• 10:05the Lancet
• 10:07showing that,
• 10:09after two years, what was
• 10:11happening to the cohort?
• 10:13Do they still have the
• 10:14prediabetes or not? But a
• 10:16good,
• 10:17sixty percent went back and
• 10:19but they were all, I
• 10:20have to say, white going
• 10:22back
• 10:23to, to the normal state
• 10:27as opposed to the African
• 10:28American that had full blown
• 10:31type two diabetes.
• 10:34And girls.
• 10:35Girls.
• 10:37The girls who are the
• 10:38most Yeah. The most at
• 10:39risk for the diabetes. Yeah.
• 10:41And your work looked into
• 10:43the genetics. Right? When you
• 10:44see in clinic, that's in
• 10:46in in our clinic, basically,
• 10:49a child with
• 10:50an elevated ALT and and,
• 10:52an old and and a
• 10:54and PDFF, an assessment of
• 10:56the fat in the liver,
• 10:58and you confirm it.
• 11:00And then then
• 11:01the problem is how on
• 11:03earth, how common is that
• 11:04at that age, and
• 11:06why why,
• 11:08are are the father and
• 11:09mother also
• 11:10having the same issues?
• 11:12And again, it's strongly dependent
• 11:14on the ethnic background of
• 11:16the kid.
• 11:18Yes. Because of the genetic
• 11:19contributions that would have come
• 11:20in. Your work was also
• 11:23done in collaboration with others
• 11:24like Mary Savoy and doing
• 11:26the very important work with,
• 11:28Bright Bodies,
• 11:29offering
• 11:30exercise
• 11:32programs
• 11:33and ways of thinking about
• 11:34physical activity and food. I
• 11:37wonder where you think that
• 11:38plays a role in the
• 11:39overall
• 11:40lifespan. I think it would
• 11:42be very important to keep
• 11:43on go going this program
• 11:45because if you catch and
• 11:48educate
• 11:49the family and the kids
• 11:51very early,
• 11:52to understand that the future
• 11:54can, you know, be tough,
• 11:57not necessarily,
• 11:58but if you do it
• 11:59early,
• 12:00I think the chance that
• 12:01really the child
• 12:03would listen
• 12:04to Mary or, you know,
• 12:06the other people that,
• 12:08are doing this program, they
• 12:10might stay with the child
• 12:11and the family and not
• 12:13get to a desperate condition.
• 12:16It's like a sponge, the
• 12:17child, you know. When they're
• 12:18very young, they absorb
• 12:20what is good for them
• 12:22and not.
• 12:23And that's what we have
• 12:24to prepare to this new
• 12:25generation.
• 12:26There's an important window of
• 12:28time
• 12:29where we can be.
• 12:30Yeah. I think that window
• 12:32is very important because these
• 12:34kids, most of them are
• 12:35growing up. You know why?
• 12:37And and and increasing their
• 12:39weight? The snacking.
• 12:41Snacking is the big problem
• 12:43that they're facing.
• 12:44Yes. But we have a
• 12:45lot of environment encouragements for
• 12:47snacking. We have to protect
• 12:49them and let them understand
• 12:51that there are good snacks,
• 12:53fairly few of them,
• 12:55but not you cannot
• 12:56live on snacking. Snacking is
• 12:58becoming the meal for the
• 13:00kids now. The way our
• 13:02bodies see food very early
• 13:03in life will program how
• 13:05we continue to see it
• 13:06later on. We have to
• 13:07be honest because we are
• 13:09reaching really
• 13:12a sad moment, I would
• 13:13say. Yes, for our food
• 13:15environment. Yes, because they are
• 13:17very attracting,
• 13:19they're full of salt.
• 13:21They know they're smarter than
• 13:23we are, these people making
• 13:24these foods,
• 13:26attracting their, their taste and,
• 13:28and things like that. But
• 13:29these are young kids. So
• 13:31having taken care of so
• 13:32many of these,
• 13:34children and and adolescents,
• 13:36through their growing years,
• 13:38what is your worst fears
• 13:39about what adulthood has for
• 13:42them?
• 13:43Well,
• 13:44I have to say that
• 13:45the experience that we had
• 13:47and we saw what was
• 13:48happening
• 13:49in the kids that were
• 13:50have been enrolled in the
• 13:52today's study, basically.
• 13:55And you you saw that
• 13:57the major complication were already
• 14:00at the age of twenty
• 14:01five there.
• 14:02That means the kidney,
• 14:04some of them have severe
• 14:06depression
• 14:08the other one was,
• 14:10the fat ear.
• 14:13So these are three conditions
• 14:14that are,
• 14:16appearing at a very relatively
• 14:19very young age.
• 14:21In the thirties,
• 14:22twenty five, thirty years. And
• 14:24again, this was,
• 14:26thanks to the,
• 14:29the help from the NIH.
• 14:31NIDDK
• 14:32really embarked in, I would
• 14:34say, twelve years of work
• 14:36we did
• 14:37in that area
• 14:38to find out that these
• 14:40kids are
• 14:41marching towards
• 14:43early complications.
• 14:44So we don't want that
• 14:46to happen. We have to
• 14:47stop that
• 14:49because I think there is
• 14:50enough knowledge for us
• 14:52to understand and
• 14:54diagnose early the the issues
• 14:56and stop it. Yes. I
• 14:58I also think of where
• 15:00the direction needs to head,
• 15:01what we need to know,
• 15:03and what next needs to
• 15:04be done.
• 15:05And you've been hard at
• 15:07work thinking about the medications,
• 15:09both for the children and
• 15:11for the adults as they
• 15:12grow up. And one of
• 15:13the studies you're doing is
• 15:14on semaglutide,
• 15:15which will have great impact.
• 15:17What things do you believe
• 15:19still need to be done
• 15:20in the field? There is
• 15:22a lot that we need
• 15:23to understand
• 15:24because even with this,
• 15:27wonderful new medication that are
• 15:29coming out,
• 15:30which,
• 15:31it's the first time that
• 15:32we we are seeing some
• 15:34very good
• 15:35improvement on the weight of
• 15:37a person
• 15:38that we never seen that.
• 15:39I mean,
• 15:40very rarely.
• 15:43And and and not only
• 15:44it's just the weight that
• 15:46we are addressing, for example,
• 15:48and this is valid
• 15:50both, in kids and in
• 15:52in adults. Of course, the
• 15:53adults are ahead of us
• 15:55because, it takes time really
• 15:58to convince,
• 16:00that there is a young
• 16:02a younger population that needs
• 16:04also some help.
• 16:06So we started to use,
• 16:08for example, in this trial
• 16:09that we're doing now,
• 16:12is,
• 16:13with semaglutide,
• 16:15like I said, Ozempicor
• 16:17or Wegovy.
• 16:18We chose Wegovy because it's
• 16:20the focus is on obesity.
• 16:22But we it's a mechanistic
• 16:24study that we're doing because
• 16:26we wanna see whether the
• 16:27medication
• 16:28is also affecting,
• 16:30fat in the liver
• 16:31and the prediabetes.
• 16:33The study that we are
• 16:34doing hopefully
• 16:36will show whether, you know,
• 16:38the fat in the liver
• 16:39and and, the prediabetes
• 16:41are sensitive to this, the
• 16:44semaglutide.
• 16:45And, and
• 16:47that would be a major
• 16:48step, I would say, in
• 16:49the field.
• 16:51We need better medication
• 16:53and just like, you know,
• 16:55the blood pressure or other
• 16:56issues that we take forever,
• 16:58these medication,
• 16:59We have to convince
• 17:01that this is totally normal
• 17:02to treat overweight and obesity
• 17:04with an injectable or none.
• 17:06Another big issue is the
• 17:08cost of the medication
• 17:10so that we forget about
• 17:12it, but many of us
• 17:13will never be able to
• 17:15afford it.
• 17:17So there has to be
• 17:18something down
• 17:19because,
• 17:21it's it's
• 17:23to see obesity or overweight
• 17:25as a disease is serious.
• 17:28And the drug that they
• 17:29are making,
• 17:31the the new drugs are
• 17:33all injectable and too too
• 17:35expensive for us for any
• 17:37one of us.
• 17:38So I don't know the
• 17:39future. This is happening particularly
• 17:42in US.
• 17:43In Europe, I know it's
• 17:44totally different. The cost is
• 17:46much less
• 17:47than what we are
• 17:49fighting for now here in
• 17:51the US.
• 17:52Yes. And I appreciate very
• 17:55much,
• 17:56your encouragement. I love talking
• 17:58to you and and to
• 18:00continue the research that we
• 18:01did because many of these,
• 18:04women
• 18:04basically need your help a
• 18:06lot
• 18:07to avoid much more complicated
• 18:11situation that believing in. Thank
• 18:13you, doctor Caprio, for this
• 18:15time with you. Thank you
• 18:16all.