Obesity/Insulin and Cancer
July 20, 2020Information
July 19, 2020
Yale Cancer Center
visit: http://www.yalecancercenter.org
email: canceranswers@yale.edu
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- 00:14Welcome to Yale Cancer
- 00:15Answers with your host
- 00:17Doctor Anees Chagpar.
- 00:18Yale Cancer Answers features
- 00:20the latest information on cancer
- 00:22care by welcoming oncologists and
- 00:24specialists who are on the forefront
- 00:26of the battle to fight cancer.
- 00:28This week is a conversation about
- 00:30the role of obesity and insulin in
- 00:32cancer with doctor Rachel Perry.
- 00:34Doctor Perry is an assistant professor
- 00:36in Medicine and Endocrinology
- 00:38and cellular and Molecular Physiology
- 00:40at the Yale School of Medicine,
- 00:42where doctor Chagpar is a
- 00:45professor of surgical oncology.
- 00:47Rachel,
- 00:47maybe we can start by talking
- 00:49a little bit about obesity.
- 00:55They talk about it
- 00:57being like the other pandemic.
- 00:59It's really something that's
- 01:01prevalent across the world,
- 01:02is that right?
- 01:05Yes, that is absolutely true.
- 01:06So at this point we're coming up on close
- 01:10to 50% of Americans who are obese and
- 01:13large numbers really worldwide as well.
- 01:15And with that obesity is a problem
- 01:18in and of itself, it increases
- 01:21the risk of cardiovascular disease,
- 01:23stroke and cancer which we will discuss
- 01:24today and other conditions,
- 01:26but it also brings with it an
- 01:28increased risk of type 2 diabetes
- 01:36which can be caused by obesity and
- 01:39is expected to effect 100% of
- 01:41Americans, or would affect 100%
- 01:42of Americans if current trends
- 01:44continue by the year 2050.
- 01:46That really is mazing.
- 01:49So that tells us we need to do
- 01:51something to intervene here.
- 01:53Two statistics that
- 01:54you put out in a single sentence
- 01:57that just completely blew me away.
- 01:59The first is that almost half of all
- 02:02Americans are obese and all of us are
- 02:05going to end up with Type 2 diabetes
- 02:08in 30 short years,
- 02:10that's incredible.
- 02:11I just have to correct myself.
- 02:14Overweight or obese, almost 50%.
- 02:16I was gonna ask about that.
- 02:19So what really is the definition of obesity?
- 02:22I mean are we talking about
- 02:25that last five or 10
- 02:28pounds that everyone has to lose?
- 02:31Or are we talking about people
- 02:33who are seriously several pounds
- 02:35or several 100 pounds overweight?
- 02:37Somewhere in between the two.
- 02:40Technically, obesity is defined
- 02:42as a body mass index over 30,
- 02:44and that really corresponds to
- 02:46being about 30 to 50 pounds,
- 02:48closer to 50 pounds over
- 02:49our ideal body weight,
- 02:51and so we're not talking about,
- 02:53you know the last five or
- 02:5510 pounds from high school.
- 02:56That may put us into the overweight category,
- 02:59but we don't need to be hundreds of pounds
- 03:02overweight to be in that obese category.
- 03:05That can really increase our risk
- 03:06of a number of health conditions,
- 03:09and so one of those conditions is cancer.
- 03:12Can you give us a metric?
- 03:15How much does obesity really
- 03:17increase your risk? I know a
- 03:19lot of people worry about cancer,
- 03:21I mean certainly they worry
- 03:23about diabetes and heart disease,
- 03:25all of those are some of the
- 03:28key killers of Americans these days.
- 03:30But how much does obesity
- 03:32really impact cancer?
- 03:33And does it affect all kinds of
- 03:36cancer or just a select few?
- 03:38Well, those are
- 03:39both great questions and in the
- 03:41answer to the first question,
- 03:43how much does obesity affect cancer risk,
- 03:45it's difficult to answer because it
- 03:48really depends on the tumor type
- 03:50and so I'm going to answer your
- 03:52second question first and that is
- 03:57at this point there are 13 tumor types
- 03:59that the Centers for Disease Control have
- 04:02associated with obesity and that means,
- 04:05with obesity increasing the risk and
- 04:07causing a worse prognosis of those tumor
- 04:09types and those include breast cancer,
- 04:11ovarian, uterine, renal,
- 04:12pancreatic, thyroid, colorectal,
- 04:13as well as several others.
- 04:16And but there are few tumor types
- 04:18where there's no risk of obesity,
- 04:20and we really don't understand what causes
- 04:23some tumor types to be worse with obesity,
- 04:26and other tumor types not to be
- 04:28worse within the tumor types that
- 04:31are associated with obesity,
- 04:32there are some where obesity brings with it
- 04:35a relatively lower risk in breast cancer.
- 04:37I believe the increase is about
- 04:4020 to 30% of an increased risk
- 04:42with obesity, still very significant
- 04:44but smaller than others.
- 04:46Whereas with pancreatic cancer,
- 04:47risk is a couple fold, ovarian cancer as well,
- 04:50a couple fold greater risk with obesity.
- 04:53So as I said
- 04:55it really depends on the tumor type.
- 04:57But because these 13 cancer types that
- 05:00are associated with obesity are among
- 05:02the most prevalent cancer types out there,
- 05:04it really translates to a
- 05:06significant excess risk.
- 05:07From an epidemiological standpoint
- 05:09that comes
- 05:10with obesity.
- 05:11And we really don't know why.
- 05:14Even 20 to 30% increased risk of breast
- 05:17cancer seems pretty significant to me.
- 05:19But why is that 20 to 30%
- 05:22but in ovarian cancer we're
- 05:24talking about more like 200%?
- 05:26Do we know why that is?
- 05:29Why it is that obesity effects more
- 05:31cancers in some situations than in others?
- 05:34We really don't,
- 05:36and that is a tremendous open question
- 05:38that we need to figure out.
- 05:41Because if we could figure out
- 05:43why obesity worsens certain
- 05:45cancer risks worse than others,
- 05:47then perhaps we would have a better handle
- 05:50on why obesity increases cancer risk
- 05:52at all, and that would be the
- 05:55target that would be where we
- 05:57can intervene in this process.
- 05:59A lot of labs, mine included as well as
- 06:02many others are working on this
- 06:04question to try to uncover number one,
- 06:07why are certain tumor types affected
- 06:09and not others and #2 why are
- 06:11certain tumor types affected worse than
- 06:14others because there's really going
- 06:16to be a major epidemiological role for
- 06:18uncovering that information.
- 06:21Do we know what exactly or how exactly
- 06:24obesity increases your risk of cancer?
- 06:29We're still working on that and there
- 06:31have been a number of potential mediators
- 06:33that people have thrown out there.
- 06:36One that my lab studies is
- 06:38insulin and related to that,
- 06:40insulin-like growth factor one.
- 06:41The concentrations of these molecules
- 06:43increase with obesity and we and others
- 06:46have shown that in vitro those molecules
- 06:48can increase tumor cell division.
- 06:50We can talk a little bit later about
- 06:53the mechanism by which that may occur,
- 06:55if you'd like.
- 06:56But there have been a number of other
- 06:59factors that people have proposed as well,
- 07:02including inflammatory cytokines.
- 07:03Obesity is a pro inflammatory
- 07:05state and so inflammatory cytokines
- 07:07are up in obese individuals.
- 07:08There's leptin, a protein that is
- 07:11secreted by the fat and has been shown in
- 07:14certain models to accelerate tumor growth.
- 07:17There are other hormones that
- 07:19may be involved, we
- 07:21mentioned insulin,
- 07:22but also potentially Glucagon,
- 07:24Adiponectin.
- 07:25And any and all of these have
- 07:28been shown in vitro,
- 07:29so in cell culture studies,
- 07:31to accelerate tumor growth,
- 07:32and there's been increasing
- 07:34work in mice in humans,
- 07:35it's a little bit more difficult
- 07:37to tell the answer because you know
- 07:39a patient comes in with cancer.
- 07:41you can't do all these types of
- 07:44interventions that we're able to
- 07:45do in the lab to really be able to
- 07:48pick out certain positive factors,
- 07:50but all of these hormones and cytokines
- 07:52that I just listed correlate with
- 07:54tumor appearance and progression.
- 07:58And a point
- 07:58I wanted to make related to the
- 08:01role of obesity,
- 08:02we talked about how obesity may increase
- 08:04the risk of certain types of cancers,
- 08:07but it also worsens the progression
- 08:09and increases the rate of recurrence
- 08:11of the cancer.
- 08:12So when we say that obesity may increase
- 08:15the risk of breast cancer by 20%,
- 08:18it also worsens the prognosis of
- 08:20someone who's already diagnosed with
- 08:22breast cancer as well as increasing
- 08:24her risk of recurrence, so that 20%
- 08:26increased risk is really not just 20%.
- 08:29Because the increased risk continues
- 08:31down the line and we really need
- 08:34to figure out what the reason for
- 08:37that is so that we can intervene in
- 08:39a mechanistically driven manner.
- 08:41And I think that the
- 08:44other problem now that you mention
- 08:46it, is the fact that obesity really
- 08:48increases the risk of recurrence,
- 08:50particularly in breast cancer and
- 08:52maybe in other cancers as well.
- 08:54Some of the therapies that we use
- 08:57actually make you gain weight, so
- 08:59many breast cancer survivors actually
- 09:02gain weight during therapy and then on
- 09:05top of that that weight gain or that
- 09:07obesity increases their risk of recurrence.
- 09:10So have people looked at that?
- 09:14I mean, is the weight that you gain
- 09:16during therapy versus simply just
- 09:18being overweight to begin with?
- 09:20Does that make a difference
- 09:22to your recurrence?
- 09:23If you were normal weight,
- 09:25for example, when you were diagnosed and
- 09:28then you gained weight with your treatment,
- 09:30does that increase your risk of
- 09:33recurrence because that weight gain
- 09:35was related to your treatment versus
- 09:37if you were overweight to begin with?
- 09:40In fact it does.
- 09:42So people have looked at this specifically,
- 09:44the change of weight during
- 09:46the course of treatment and those
- 09:48who gain weight during treatment.
- 09:49Actually specifically for
- 09:50breast cancer as you mentioned,
- 09:52are in fact at a higher risk
- 09:54of recurrence of their cancer,
- 09:56and so that's something that absolutely
- 09:58needs to be kept in mind during therapy.
- 10:00Now that said,
- 10:01it's not as simple as it may appear,
- 10:04because those who lose weight
- 10:05during treatment
- 10:07also have a poorer prognosis.
- 10:08This gets into the issue of cancer cachexia.
- 10:11So when patients are
- 10:12being treated for cancer,
- 10:13have cancer and they lose a
- 10:15significant amount of weight,
- 10:17a very large amount of weight so
- 10:19that they lose a lot of fat and
- 10:21start to lose muscle as well,
- 10:23those patients are also at
- 10:25higher risk for poorer outcomes,
- 10:26and so we can't simply tell people,
- 10:28just go and lose weight,
- 10:30and that's really why we need to
- 10:32understand mechanistically what this
- 10:33link is between obesity and cancer,
- 10:35so that instead of telling people,
- 10:37oh, just go and lose weight,
- 10:39we can give them a mechanistically
- 10:41driven intervention
- 10:41that may help mitigate that risk of obesity,
- 10:44while not predisposing them
- 10:46to cancer cachexia.
- 10:47So let's unpack that a little bit more.
- 10:50What do you mean by a mechanistically
- 10:53driven intervention?
- 10:56We want to understand what the molecule is or
- 10:58molecules are that are responsible for
- 11:00this link between obesity and cancer.
- 11:03For instance, if the link is
- 11:05at least in part insulin,
- 11:07one of my favorite hypothesis,
- 11:09there are ways that we can lower insulin
- 11:12while not forcing a patient to lose weight.
- 11:15There are different drugs that work
- 11:18in different ways that would all lower
- 11:21circulating insulin and that would
- 11:23not require the patient to go on a
- 11:25restrictive diet or put themselves
- 11:27at risk for cancer cachexia syndrome.
- 11:30Similarly, if the link were
- 11:32certain inflammatory cytokine,
- 11:33there are various antibodies that
- 11:34are being developed to block certain
- 11:37inflammatory cytokine action,
- 11:38and so we could potentially give
- 11:40folks an antibody to that particular
- 11:43cytokine that might lower their risk,
- 11:45while again,
- 11:46not requiring them to lose weight.
- 11:48So it would just allow us to more safely
- 11:52intervene in this link between
- 11:54obesity and cancer
- 11:55if we could understand
- 11:56exactly what mediates it.
- 11:58Except that they'd still be at
- 12:00increased risk of heart disease
- 12:02and diabetes if they were
- 12:04overweight, right?
- 12:05Yes, certainly weight loss
- 12:06within a healthy range,
- 12:08so not becoming underweight but
- 12:10weight loss within a healthy
- 12:12range is probably going to be the
- 12:15best way to mitigate this risk.
- 12:17Overall though it may be very
- 12:19difficult during cancer treatment,
- 12:21as you mentioned.
- 12:22Cancer treatment tends to
- 12:23cause people to gain weight,
- 12:25and so during that short period of
- 12:27time it may be better to focus on
- 12:30what we can do from
- 12:32a cancer standpoint,
- 12:33to mechanistically intervene in this
- 12:35link between obesity and cancer,
- 12:36rather than focusing on weight loss.
- 12:38But long term from a population standpoint,
- 12:41absolutely we should all be encouraging
- 12:43our patients and ourselves to
- 12:45maintain a healthy weight.
- 12:47Rachel, I want to dig a little bit deeper into
- 12:50what your lab is doing in terms of
- 12:52insulin and its link to obesity.
- 12:55One of the statistics that you
- 12:57gave us at the top of the show,
- 13:00which was the link between
- 13:02obesity and diabetes,
- 13:03was just mind blowing to me.
- 13:05So talk a little bit about that
- 13:08and how insulin plays into that,
- 13:10as well as into this
- 13:12whole concept of obesity.
- 13:14Yeah, so my training was
- 13:16in straight metabolism.
- 13:18I studied diabetes and substrate
- 13:20metabolism during my graduate work
- 13:22and my post doc and we developed
- 13:24methods to be able to assess
- 13:26metabolism in different tissues and
- 13:28different settings and so one of
- 13:30the hormones that we focus on in
- 13:33the metabolism world is insulin.
- 13:35Insulin is secreted by the endocrine
- 13:37pancreas when we eat a meal.
- 13:40When blood sugar levels go up,
- 13:42insulin is secreted.
- 13:43Insulin helps ourselves to take up
- 13:45glucose or sugar so that the sugar
- 13:48is taken out of the bloodstream
- 13:50and into the tissues.
- 13:52And when we do that,
- 13:54the tissues or even tumors in
- 13:56certain cases can use that sugar as
- 13:58fuel for themselves while lowering
- 14:00blood glucose concentrations.
- 14:02So in diabetes,
- 14:03that process doesn't happen efficiently.
- 14:05People tend to become insulin resistant,
- 14:08so their bodies don't respond as well
- 14:10as they need to insulin and so it
- 14:14either needs to be given by injection,
- 14:17or certain interventions need to
- 14:18take place to allow the body to
- 14:21respond better to insulin and
- 14:22the work that we've been doing
- 14:24in my lab in the last
- 14:27several years has been specifically
- 14:28looking at this link between insulin,
- 14:31obesity and cancer.
- 14:32I think there's a lot more
- 14:34we need to learn about obesity,
- 14:37insulin, and cancer,
- 14:38and how all of that plays together.
- 14:40But first we need to take a
- 14:42short break for a medical minute.
- 14:44Please stay tuned to learn
- 14:46more about obesity, insulin,
- 14:47and cancer with my guest doctor Rachel Perry.
- 14:51Support for Yale Cancer Answers
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- 15:03More information at astrazeneca-us.com.
- 15:06This is a medical minute about genetic
- 15:09testing which can be useful for
- 15:11people with certain types of cancer
- 15:14that seem to run in their families.
- 15:16Patients that are considered at risk
- 15:19receive genetic counseling and testing so
- 15:21informed medical decisions can be based
- 15:24on their own personal risk assessment.
- 15:26Resources for genetic counseling and
- 15:28testing are available at federally
- 15:30designated comprehensive cancer centers.
- 15:32Interdisciplinary teams include geneticists,
- 15:34genetic counselors, physicians,
- 15:35and nurses who
- 15:36work together to provide
- 15:38risk assessment and steps to
- 15:40prevent the development of cancer.
- 15:42More information is available
- 15:44at yalecancercenter.org.
- 15:45You're listening to Connecticut public radio.
- 15:49This is doctor Anees Chagpar
- 15:51and I'm joined tonight by
- 15:53my guest doctor Rachel Perry.
- 15:55We're talking about the role of
- 15:57obesity and insulin in cancer and
- 15:59right before the break Rachel, you
- 16:01were starting to tell us a little
- 16:04bit about how insulin really works in
- 16:06terms of causing obesity and how that
- 16:08plays into the development of cancer.
- 16:10Can you take us back a couple of
- 16:13steps and talk about insulin and obesity?
- 16:16I know insulin is a hormone
- 16:18it's made by the pancreas,
- 16:20but how does that cause us to be obese?
- 16:24And if all of us make insulin,
- 16:26how come not
- 16:28all of us are obese?
- 16:30Those are both important questions,
- 16:32and honestly, we're still not certain the
- 16:35metabolic community is still not certain
- 16:37to what extent insulin causes obesity
- 16:39versus obesity causing high insulin levels.
- 16:42We know that obesity causes high
- 16:44insulin levels because as individuals
- 16:46become more and more obese,
- 16:49they become more and more
- 16:51insulin resistant and that's due to increased
- 16:53levels of lipid or fat in various tissues.
- 16:56When we become insulin resistant,
- 16:58that means we don't respond,
- 17:00our bodies don't respond very well to
- 17:03insulin and so our body has to secrete
- 17:06more insulin to counteract that effect.
- 17:08Now the question of whether insulin
- 17:10causes obesity is very interesting
- 17:13in sort of a chicken and
- 17:15egg type of question,
- 17:16and there are a number of
- 17:19studies that do suggest that
- 17:21insulin may itself independently cause
- 17:23obesity and that's at least in large part
- 17:27because insulin causes fat deposition.
- 17:29It causes those small molecules
- 17:31of carbohydrate and fat that are
- 17:33floating by in our bloodstream to
- 17:35actually be deposited in tissues in
- 17:38subcutaneous fat depots and form larger
- 17:40and larger pieces of fat, and so
- 17:43in that regard,
- 17:44it is likely that insulin causes obesity,
- 17:47at least to some extent.
- 17:49But as I said, it's more certain
- 17:52that obesity causes hyperinsulinemia
- 17:53or high insulin levels because of
- 17:55that insulin resistance phenomenon.
- 17:57As you said,
- 17:58we all need to have insulin.
- 18:00The body knows if it doesn't
- 18:03have enough functioning insulin,
- 18:04because when we don't have enough insulin,
- 18:07our blood glucose levels get high
- 18:09without insulin action on various
- 18:11tissues, wer'e not able to take up
- 18:13enough glucose or sugar from our
- 18:16bloodstream into those tissues,
- 18:17and when that happens,
- 18:19the body senses the high blood sugar level
- 18:22and secretes more insulin to try to
- 18:24counteract the effects of insulin resistance.
- 18:27So let me get this straight, obesity
- 18:30causes you to be insulin resistant,
- 18:33so your body needs to make more insulin.
- 18:36But that insulin takes sugar from your
- 18:39bloodstream and deposits it as fat,
- 18:41which then causes you to be more obese.
- 18:45So isn't this a vicious cycle?
- 18:48It absolutely is a vicious cycle and
- 18:50we and others have shown that if you
- 18:53intervene in any step of this cycle,
- 18:56so if you intervene in the step of eating
- 18:59too many calories, if you intervene
- 19:01in secreting too much insulin,
- 19:04if you intervene in depositing that
- 19:06sugar in tissues as fat if you
- 19:09intervene in any of these steps,
- 19:11you can intervene in the cycle
- 19:13of the development of obesity.
- 19:15But yes, absolutely,
- 19:16it's a vicious cycle and this
- 19:18absolutely contributes to this
- 19:20pandemic of obesity that we have
- 19:22in our country and worldwide.
- 19:24We're
- 19:25going to get back to exactly how
- 19:27we can intervene, but let's talk a
- 19:30little bit about the cancer part.
- 19:32So we talked a little bit at the
- 19:35beginning of the show about the fact
- 19:38that obesity really does drive,
- 19:40I think it was what 13 different
- 19:42types of cancer,
- 19:43but not all cancers are affected by obesity,
- 19:46but certainly a large number of cancers are.
- 19:49So how does that happen?
- 19:51And what does insulin have
- 19:53to do with it anyways?
- 19:55Right, so as we were discussing earlier,
- 19:57I think in reality there are a
- 20:00number of different factors that
- 20:01may mediate at least part of this
- 20:04link between obesity and cancer.
- 20:06But as you said, we focus on specifically
- 20:09how insulin may fuel tumor growth.
- 20:11So, as I mentioned,
- 20:12individuals with obesity frequently have
- 20:14high circulating insulin levels because
- 20:16they tend to be insulin resistant.
- 20:18And this is indeed a vicious cycle. We
- 20:20found in a few studies, both in vitro
- 20:23so in a dish and in vivo, in mice,
- 20:26that insulin can drive tumor
- 20:28glucose uptake and metabolism, that
- 20:30actually was a little bit surprising
- 20:33initially because conventional wisdom
- 20:35has said that tumor glucose or sugar
- 20:37metabolism is constitutively high,
- 20:39so it would always be high and
- 20:42not regulated by any hormones,
- 20:44but the surprising finding that we
- 20:47and that others have also shown is that in fact,
- 20:51tumor glucose or sugar
- 20:52metabolism is insulin dependent,
- 20:54and so in mice that are obese
- 20:57and insulin resistant,
- 20:58they have high circulating insulin
- 21:00levels and this causes glucose
- 21:01uptake into their tumor cells.
- 21:03After the tumor cells take up glucose,
- 21:06it can be used in two different ways.
- 21:08It can be used for metabolism,
- 21:10so simply to provide the fuel that
- 21:13allows the cells to keep going,
- 21:15and it can also be used to make
- 21:18building blocks for cells.
- 21:19So a unique feature about tumor cells
- 21:22is that in order to be a tumor,
- 21:24these cells need to be growing
- 21:26and dividing all the time.
- 21:28They grow and divide very rapidly and they
- 21:31need building blocks to be able to do that,
- 21:34and glucose is a key fuel to be
- 21:36able to provide those building
- 21:38blocks for these tumor cells,
- 21:40and so in that way glucose
- 21:42and insulin which drives glucose uptake,
- 21:44is a key pathogenic factor in tumors.
- 21:47So let me ask you this,
- 21:49we know a lot of diabetics who
- 21:52are type one diabetics who take insulin.
- 21:55Does that mean that the insulin can actually
- 21:58be driving tumor growth in these people?
- 22:01Putting them at increased risk since
- 22:03their injecting themselves with insulin?
- 22:05You know that's a key question.
- 22:07A very important question,
- 22:09and frankly a personally relevant question, as
- 22:11I am a person with type one
- 22:13diabetes and so this is something
- 22:15that I am very curious about.
- 22:18The epidemiological evidence doesn't
- 22:19seem to support a strong role for
- 22:21exogeneous insulin, that is injected
- 22:23insulin, in type one diabetic
- 22:25individuals in driving tumor growth,
- 22:27and there could be a few
- 22:29different reasons for that.
- 22:30It is a little bit surprising,
- 22:32but what we currently believe
- 22:34is that you may need two hits.
- 22:36That is,
- 22:37high glucose and high insulin levels,
- 22:39so type one diabetic individuals
- 22:41who take as much insulin as they
- 22:43need tend not to have chronically
- 22:45high glucose levels all the time,
- 22:47and so it may be that keeping blood
- 22:49sugar normal is also very important in
- 22:52these individuals who need to inject
- 22:54insulin exogeneously to stay alive.
- 22:56But that's a question that really
- 22:58is an open question and one
- 23:00that were very curious about.
- 23:02It's also entirely possible,
- 23:03and I think this is likely that
- 23:06insulin may not be the only factor
- 23:08that mediates the effects
- 23:10of obesity on tumor growth,
- 23:11so it may be that you need high
- 23:14insulin levels to have an obesity
- 23:16affect to drive tumor growth,
- 23:18but that you also need other factors
- 23:21like inflammatory cytokines or
- 23:22leptin or other hormones.
- 23:26And in these lean type one diabetic
- 23:28individuals they may have high
- 23:30insulin levels but not these other
- 23:32factors that may be required
- 23:34to mediate the effects.
- 23:37You know, and that makes me
- 23:39think of something else.
- 23:40Some people have these benign tumors
- 23:42in their pancreas that secrete insulin,
- 23:44so it's kind of a little insulin
- 23:47factory that they've got going on.
- 23:49Are those people at increased
- 23:50risk of developing cancer,
- 23:52or is it still this,
- 23:54you need the interplay of a
- 23:56number of factors so they may
- 23:58not really be at increased risk.
- 24:00So I believe that these
- 24:02folks and I could be wrong on this,
- 24:04this isn't particularly my field,
- 24:06but I believe that those folks
- 24:08are at higher risk of pancreatic,
- 24:10at least benign tumors of other types,
- 24:13and maybe at higher risk
- 24:15of pancreatic cancer,
- 24:16so that would suggest that insulin
- 24:18may be acting within the pancreas
- 24:21as a tumor promoting factor,
- 24:23but I don't believe they're at
- 24:25substantially higher risk in other sites.
- 24:27Now this could be because it's
- 24:30my understanding that those folks
- 24:32aren't allowed to go continuously
- 24:34forever with high insulin levels
- 24:36secreted by a tumor from the pancreas.
- 24:38The tumor will be either removed, or
- 24:41treated,
- 24:42they may be treated with somatostatin
- 24:43or some other agent to prevent the
- 24:46high insulin secretion,
- 24:48but I would expect that if someone
- 24:50were chronically having high
- 24:51insulin levels from continuous
- 24:53excess secretion of insulin,
- 24:54that they would in fact be at risk and
- 24:58that is a study that we've done in mice.
- 25:01So if you take mice and put a
- 25:03subcutaneous insulin pellet into
- 25:05them so that they
- 25:07chronically have high insulin levels,
- 25:09they do develop tumors more quickly
- 25:11and do worse with the tumors
- 25:13than mice that
- 25:15don't have too much circulating
- 25:17insulin all the time.
- 25:19And when we talked about the fact
- 25:22that some of the cancers are increased
- 25:24with obesity and insulin is one
- 25:27factor that may be playing a role,
- 25:29sometimes people talk
- 25:31about this thing called insulin
- 25:33growth factor or my IGF,
- 25:34which can be found in some cancers.
- 25:37Are those related?
- 25:38So we find that insulin plays more
- 25:41of role in people who have tumors
- 25:43that have receptors, for example,
- 25:45that are more responsive to insulin,
- 25:47or is this something that is more ubiquitous?
- 25:50At least in these 13 tumor types,
- 25:52regardless of whether or not
- 25:54the tumor secretes insulin or
- 25:56insulin related growth factor,
- 25:58there does seem
- 25:59to be a relationship
- 26:00between my IGF and insulin,
- 26:02so that comes in several different ways,
- 26:05mostly that the IGF1 and insulin
- 26:07receptors are very similar and both
- 26:10molecules can activate the other.
- 26:12So insulin can activate the IG F1 receptor
- 26:15and IG F1 can activate the insulin receptor
- 26:18and so I would absolutely expect there to
- 26:21be interplay between insulin an IG F1,
- 26:24particularly in those
- 26:26IGF one expressing tumors.
- 26:27This also brings up a good
- 26:29point that I want to highlight,
- 26:32and that is that the insulin receptor
- 26:35is not ubiquitously found in tumors.
- 26:37The tumor types that are associated
- 26:39with obesity on average have
- 26:41higher insulin receptor expression,
- 26:43but that's not 100% across the board,
- 26:46but because of this cross talk between IGF,1
- 26:50and insulin that may explain some of
- 26:53the discrepancies there where a tumor
- 26:55may be at least weakly obesity associated.
- 26:58But may not have the insulin receptor
- 27:00and that may be because the IGF1
- 27:03receptor compensates for that.
- 27:04Unfortunately,
- 27:05tumors are evolved to survive very well,
- 27:07and so they've sort of developed mechanisms
- 27:10in their evolution to be able to survive,
- 27:13and one that I think
- 27:15is the redundancy of insulin,
- 27:17and IGF1 action.
- 27:19In our last few
- 27:22minutes I really want to get back
- 27:24to something you said earlier which
- 27:27was breaking the cycle of obesity.
- 27:29Can have an impact on reducing cancer risk.
- 27:32I wanna make sure I got that straight.
- 27:35So if you're overweight and you
- 27:37decide to lose weight by cutting
- 27:40calories or exercise,
- 27:42that actually can reduce your cancer risk.
- 27:45Is that right?
- 27:46Absolutely, epidemiologically,
- 27:47even losing weight within the last
- 27:49couple years reduces your cancer risk,
- 27:51and so it's best
- 27:54of course, if we're normal weight,
- 27:56healthy weight throughout our lives.
- 27:58But it absolutely can have a
- 28:00huge impact to lower cancer risk.
- 28:02Losing a little bit of
- 28:04weight at really anytime.
- 28:06And you know the other point I want
- 28:09to highlight is we don't have to be
- 28:12back to our high school body weight.
- 28:15This is a case where
- 28:17Losing 5 to 10% of body weight
- 28:19if you're an overweight or obese
- 28:21individual can actually almost fully
- 28:23normalize your insulin sensitivity,
- 28:26and so that can be
- 28:28predicted to almost fully normalize
- 28:30or reduce the excess risk of obesity,
- 28:33and so that is something where
- 28:36that loss of five to 10% is something
- 28:39that would be much more achievable
- 28:42then returning to a quote
- 28:43unquote healthy weight for a lot of
- 28:46individuals.
- 28:48Doctor Rachel Perry is an assistant professor in
- 28:50medicine and Endocrinology
- 28:51and cellular and Molecular Physiology
- 28:53at the Yale School of Medicine.
- 28:56If you have questions,
- 28:57the address is canceranswers@yale.edu
- 28:59and past editions of the program
- 29:01are available in audio and written
- 29:03form at Yalecancercenter.org.
- 29:04We hope you'll join us next week to
- 29:07learn more about the fight against
- 29:10cancer here on Connecticut public radio.