October 15, 2021 Liver Disease and Diabetes

welcome everyone uh thank you for tuning

in my name is brooks roach i am a

diabetes education specialist with

diabetes canada and i'd like to begin by

welcoming you our viewers and

acknowledging that the land from which

i'm calling is the traditional and

unseated territory of migma people so

wherever you are joining this webinar

from i would invite you to just take a

moment and reflect on

the traditional and

and

traditional inhabitants of the lands we

now call canada

i'm really excited to to be with you

today and to present this uh really

exciting collaboration that we've been

developing with a wonderful partner the

the canadian liver foundation um and and

the intent of this webinar as you'll

hear is to discuss some of the

fascinating intersections and prevent to

present you with some actions and

strategies uh recognizing the link

between liver disease and diabetes and

with that i'd like to hand it over to my

colleague from the canadian liver

foundation nem take it away

thank you brooks um hello everyone uh

good afternoon and uh good morning and

good day for everyone who are who is

joining us today for this wonderful

opportunity webinar um as brooks did

mention uh my name is nem i am one of

the senior managers of support and

education the canadian river foundation

i would also like to acknowledge that

our national office for the canada

foundation in markham ontario is

situated upon traditional territories of

the anishinabe peoples and of the haduno

sami peoples covered by the upper canada

treaties

we are joined today by two wonderful

experts we have dr mark swain a

professor of medicine of the professor

medicine and head of division of

gastroenterology and hepatology at the

university of calgary as well as dr

marianne doyle endocrinologist and

associate scientist in clinical

epidemiology at the ottawa hospital an

assistant professor of medicine at the

university of ottawa

welcome and thank you both for being

here

so as brooks mentioned we are going to

be diving into a important conversation

evaluating and discussing relationships

between

liver disease and diabetes and our

experts will be answering some key

questions that we've been hearing from

patients uh we'll also be getting

questions from our viewers and some

questions have already been submit

submitted so thank you everyone who

submitted the questions ahead of time

and you can also ask any of your

questions by replying in the comment

feed below

without further ado i will be turning

the mics over to our experts

great thank you for inviting me today

i'm marianne doyle and um and although

i'm an endocrinologist

here in ottawa i have had an interest in

chronic liver disease probably for the

last 10 to 15 years my interest started

initially with infectious liver disease

so hepatitis c and

specifically hepatitis c and the

relationship between

infectious liver disease and the

incidence and prevalence of diabetes and

that got me thinking about how

really in endocrinology and diabetes

management we really don't pay much

attention to the the liver and got me

shifted my focus i think also too as we

started finding treatments for hepatitis

c there was less interest in that area

but

it shifted my interest more to metabolic

liver disease and the association with

with diabetes

and uh and so i'm happy to be here to

talk with dr swain about that today and

um and answer any questions that anyone

may have

and uh hi everyone i'm mark swain i'm in

calgary and uh uh actually like marianne

my my interest uh traditionally was more

in

sort of infectious types of liver

disease and and autoimmune types of

liver disease and in fact

um uh

fatty liver disease was something that

was actually really

not it was kind of ignored actually in

the liver world for a very long time but

it's become quite clear that not only is

it an entity on its own but it's also

uh a driver for other other forms of

liver disease and making and often makes

them uh more aggressive uh but also the

it's become very clear that it's uh

linked to uh to uh uh mainly type two

diabetes uh and uh and so this

this is a natural kind of uh discussion

uh because

type two diabetes and and and fatty

liver disease are are often not talked

about at the same time but but in fact

they should be because

as you'll see as we go through our uh

our discussion today is that they they

intertwine very

robustly and in fact they need to be

discussed

really together

so thanks for joining us

great thank you

dr swain so i'm going to just start with

some

broad facts about diabetes in canada

i think over the last two years we've

really focused on covid but in all of

that there's been another silent um

disease that's been grumbling along

and i think um we need to take

just a minute to kind of think and look

back at some of those numbers so

interesting one in three canadians in

canada so about 11 million canadians are

actually living with diabetes or

pre-diabetes today and that's an

enormous amount of people

and the burden on our sis our health

care system is is phenomenal um and and

we know that there's a lot that we can

do to prevent this

um and that a canadian is diagnosed

every three minutes so in this talk

today during this hour about 30

canadians will be diagnosed with

diabetes and and again um this

being um

that it is a preventable disease um

really there is a lot more that we can

do

um to mitigate that

um about one and a half canadians one

half million sorry not one and a half

canadians one and a half million

canadians um actually have type 2

diabetes and don't know it and that's

because it really is

a silent disease people can have high

blood sugars for years and years and

years and and not not be aware of it

and then there are about six million

canadians that are living with

pre-diabetes half of which will go on to

develop type 2 diabetes but with

appropriate preventative care we can

prevent that we can change that course

and the real concern with it with

diabetes um is that

it's the the complications that come

from it um and come from the high blood

sugar so we know that it causes the

leading cause of blindness it causes 30

percent of strokes that we see 40

percent of heart attacks

50 of kidney failure that requires

dialysis and then 70 of all

non-traumatic leg and foot amputations

so a real health care concern um that we

can do more to uh to change the the

course of the disease

so i'm going to take just a little step

back here and just go back to some

basics about what is diabetes diabetes

is elevated blood glucose levels

and to understand that we really need to

think about what is plasma glucose and

it's basically a a fine balance between

glucose entering the circulation and

then glucose being removed from the

circulation so what we eat versus the

energy we expend

um and the body requires a constant

source of energy so even though we're

sleeping our body is still using glucose

in our blood and we only eat

intermittently so that balance is

regulated very tightly in fact um by

hormones that are secreted from the

pancreas so we have insulin is which we

talk about most often but also glucagon

and

insulin and glucagon work together to

make sure that that blood glucose level

is is well controlled but there's also a

number of other players that we um that

we need to consider when we're talking

about diabetes so can we move on to the

next slide

so some of the key players are the brain

which in fact uses a

significant amount of our blood um

glucose

levels or

amounts um but it's able to use glucose

independent of insulin it's the only

only organ that is

then there's the pancreas which we um

that which is a key player in in

regulating glucose metabolism through

the secretion of both insulin and

glucagon and again that fine balance

then we have our muscles um which are

important in terms of when we were ready

to exercise and be active then our

muscles are able to use that energy also

able to store some of that energy

also able to use some of that

those circulating blood glucose um with

independent of insulin so the more

active you are the more your your body

will be efficient in in using that that

circulating glucose the kidney is a

really important

player in terms of excreting glucose so

the when glucose levels get high the

body the kidney is able to excrete more

more glucose

and then adipose tissue important in

storage when there's high levels of

glucose around our body's able to

convert fat and store it for a time

where we may need that and store it as

adipose tissue and then what we're pro

we're most interested in today is the

liver and that's probably the the player

that's least talked about but probably

the biggest player in glucose metabolism

so not only is the liver key at making

sure that the body has the proper

glucose levels it needs when it comes

time for

activity energy

is needed

but it's also able to store large

amounts of

glucose and so probably one of the

biggest key players but often neglected

and not focused on as much until

recently

i'm also going to just take a step back

and we we often talk about diabetes be

as as if it's all one disease and

and honestly until recently we have

actually treated um

both type 1 and type 2 diabetes as if

they are um one in the same and i'll get

into the reason the rationale for that

but i think it's important to realize

that there are two separate diseases and

although they're they're both um

referred to as diabetes two very

separate diseases so type one diabetes

is actually an autoimmune disease where

you get destruction of the beta cells

and beta cells are the cells in the

pancreas that are important in producing

insulin and when those get destroyed the

body's no longer able to produce insulin

and no longer has the insulin around

circulating that is needed to help the

body and the cells in the body the liver

take up those circulating glucose levels

and as a result the glucose increases in

the blood and and then becomes toxic to

the the circulating cells and organs

um the exact cause is really not well

understood it's probably a genetic

combination of genetic and perhaps

environmental factors that are

contributing um to this and so really

this is an insulin deficiency problem

and the treatment for this is insulin

in contrast type 2 diabetes the body

does make insulin it's not it has the

cells that are making it or not haven't

been destroyed or anything but the body

can't use it properly it also then

starts over time those cells may start

to fail and produce less insulin

and there's also so there's also there's

insulin resistance but also an

insufficient production to overcome that

insulin resistance

when we're talking about causes or risk

factors we know that as people get older

this seems to be more prevalent obesity

definitely contributes to this

we know that a sedentary lifestyle can

contribute to it there's definitely

certain genetics and it's probably

multiple different genes that are acting

simultaneously

um and then ethnicity definitely

contributes to it the interesting thing

about this is that with lifestyle

modification weight loss

um

certain oral medications and insulin we

can change that

and that's our treatment so it's not

solely oh your insulin isn't working we

need to give you more well that which is

what we sometimes do but that isn't our

main

treatment and it isn't our first our

go-to treatment

type one diabetes is really not

preventable at this point because we

don't fully understand the cause and it

really only accounts for about 10 of the

cases in contrast type 2 diabetes is

preventable um in in many cases and it

accounts for about 90 of diabetes cases

mary and pardon the interruption we just

have a few folks who are commenting in

on facebook that they're not able to

actually see the the live feed so if you

don't mind we're just going to pause for

a moment and reconnect to that live

stream sure

there's not a zoom webinar without a

technical issue

okay folks it looks like we are back so

i will uh

hit next slide and then hand the reins

back over to you

all right great

um so i just was talking about the

differences between type 1 and type 2

diabetes and really our focus today is

going to be on type 2 diabetes and not

the association between type 2 diabetes

and

metabolic liver disease because they're

probably

uh and dr swain will go into to this a

little bit more but um

either

in intertwined or related or maybe even

spectrum of the the same disorder and so

that's what our focus is really going to

be on and so when we're looking at and

this is just a little bit of a diagram

to sort of explain

what's happening when we we have type 2

diabetes so

as i mentioned there's insulin

resistance

and as a result you get decreased uptake

of glucose in in the body so a decrease

uptake in the muscle decrease uptake in

adipose tissue you get higher levels of

glucose circulating you also have beta

cell dysfunction

and so the

the beta cells the insulin secreting

cells in the pancreas are not able to

overcome this resistance and as a result

there's less insulin there's still

insulin but there's less insulin

circulating for the level of the

the blood sugars are at and as a result

all of these factors contribute to

higher blood sugar levels

um the

liver is also

not recognizing necessarily that there

is

um

high these high levels because the body

is is in need of glucose and not

entering the cells so it actually also

leads to increased glucose output so

there's basically dysregulation between

the pancreas the liver the muscle and

adipose tissue so all of the key players

in in the body

in glucose metabolism

and what does that what

why does this matter so we know that

with higher blood sugar levels and this

is important in type 1 and type 2

diabetes but when the blood sugar levels

are high over time

these high levels of glucose are

actually toxic to the cells and organs

of our body and as a result this leads

to

a lot of macrovascular complications so

it puts people at higher risk of stroke

heart disease and hypertension

it leads to

peripheral vascular disease so narrowing

of the blood vessels

that supply the feet and toes and

fingers and and arms and as a result

can lead to increased risk of infection

also increased risk of amputation

there's also microvascular complications

so the smaller vessels that supply the

eye um are quite sensitive to high blood

sugar levels and as a result this can

lead to changes in the retina so the

back of the eye as well as increased

risk of cataracts

high circulating glucose levels are also

quite toxic to the kidneys and as a

result this puts people at risk for a

renal disease

and over time slowly the kidneys start

to fail and they're no longer able to um

to function and and

clear the blood like they should

and and patients end up

needing dialysis

it also destroys the small um little

nerves that supply that um we depend on

for

uh sensitivity in our our feet and our

hands and our toes and as a result again

leads to risk of infection endless risk

of injury to the feet and subsequently

amputation

and we know if we control blood sugar

levels and so our goal has been with

with management of both type 1 and type

2 diabetes is to lower those glucose

levels

and for the most part we we do that

through

a number well with type 2 diabetes

lifestyle modification and then

medications and i'll go into a little

bit more detail in a moment um after we

hear a little bit about from mark uh dr

swain about um why this is important

thanks marianne um so

when when you saw that that overview

that marianne showed the picture of of

the complications uh of type 2 diabetes

that really

that's a traditional picture and that

liver is not actually included on that

and so uh hopefully we're going to uh

um

uh

i i guess stress today that the liver

actually is

something that's that's intimately

involved in type 2 diabetes and what

what happens in in in the setting of a

number of things but type 2 diabetes one

of them is that you can develop fat in

the liver and if you look on the left

the liver becomes kind of yellow and a

bit swollen where normally it's kind of

pinky

and if you look at in a liver biopsy

it's sort of sort of microscopically the

normal liver is on the left you can see

nice little sort of liver cells which

are pink and they've got the nucleus

which is the blue bluey part in the

middle and they're all in little chains

like little little

blocks that are that are built in chains

and the blood flows between them and

that's where the exchange of nutrients

happen uh they're so important to

metabolism but if you look on the right

that's a liver that's that someone that

has or a biopsy from someone that has

fatty liver

and you can see the liver cells are

swollen and the white areas that look

like balloons they're actually cells

that have been expanded to be a balloon

shape uh by fat that's been deposited in

the cells and and and that fat can

actually lead to liver injury next slide

next slide please yeah thanks

um and so first of all so what is nafld

i mean not this is a a word that we use

today we use the word nash as well and

so it's important to define them so so

nafld is uh is a short form for what uh

the term non-alcoholic fatty liver

disease and so that means it's

essentially

a diagnosis a diagnosis of exclusion so

you remove the other cause of liver

disease including there's a certain

cutoff amount of alcohol consumption on

a daily basis that once you once you go

over that that level then then that

drives what we call alcohol related or

alcoholic fatty liver disease and uh and

how much alcohol that is is quite hotly

debated

however

you also can develop something called

nash

and nash is short form for

non-alcoholics theatro hepatitis

and and that is a very fancy term but

essentially steato just means fat and

hepatitis means inflammation so this

means

uh when when the fatty liver has become

a condition where the liver is inflamed

and being damaged

next slide

and and so when one's talking about

nafld or non-alcoholic fatty liver

disease it's important to recognize

they're actually talking about a

spectrum of liver diseases and that

ranges from fatty liver as i just showed

you that picture

to nash so nash is is is the fat

accumulating the liver that's associated

with inflammation or damage or

destruction of liver cells

and that destruction of liver cells can

lead to scarring in the liver and then

if you get enough scarring in the liver

that's what we call cirrhosis and if you

have enough cirrhosis then you can get

liver failure and also

and need a liver transplant or or it's a

it's a cause of liver related death but

also it predisposes people to developing

liver cancers and once you have

cirrhosis you have about a three percent

chance per year of developing a liver

cancer but uniquely in fatty liver

disease which is different than all the

other pretty much all the other liver

disease except for maybe hepatitis b

people can go just from having fatty

liver without cirrhosis even to

developing liver cancers and the

pictures at the top here just shows if

you look at the one on the right that

the pink is is is liver cells

and the blue is scar tissue and you can

see that the scar tissue or the blue is

surrounding the pink to make it look

nodular or like like lumps and that

lumpy bumpiness is what when people talk

about cirrhosis that's what they're

referring to is this sort of the size

the outside of the liver and inside all

through the liver becomes lumpy bumpy

and hard

next slide please

and so what are the main causes of of

non-alcoholic fatty liver disease well

as marianne said and this is often not i

think has been poorly recognized is that

diabetes is the main driver

and obesity those are the two

critical drivers of non-alcoholic fatty

liver disease although these other uh

things are cause there's some

medications that can lead to it there

are some genetic changes that can that

can drive fatty liver disease um people

that have high cholesterol or high

triglycerides which is another fat in

the blood they can also develop fatty

liver disease uh and

not usually an issue

in

western countries but rapid weight loss

can also

rarely cause uh uh fatty liver

next slide

uh and when you when you look at fatty

liver uh most people say oh i've never

heard of fatty liver disease i've never

heard of nafld or nash but in fact if

you look in north america so with a red

circle around you can see about 24 25 so

one in four people has fatty liver

disease

uh so it's extremely common it's growing

every year the the

the number of people in our society that

have fatty liver is growing

and when you look at nash so this

inflammation of the liver that's

associated with fat in the liver

that's also associated with the

development of scar tissue that affects

about two to three percent of the

general population

next slide

so what's the relationship between type

2 diabetes and math

next slide so so so mary ann showed that

the livers kind of plays an important

role in uh insulin sensitivity insulin

metabolism glucose metabolism um but but

there

there's growing evidence that that

there's a link between type 2 diabetes

and nafld and that is that that the

resistance to the effects of insulin the

body

which is really as marianne said

is the hallmark of type 2 diabetes so

the tissues don't respond to insulin

normally

that actually also leads to fat

accumulation in the liver so the

steatosis or non-alcoholic fatty liver

and when you look at people that have

type 2 diabetes

there's a

spectrum of studies that looked at this

but between 45 and probably closer to 75

percent of people with type 2 diabetes

have have have naffed or non-alcoholic

fatty liver disease

and this fat that accumulates in the

liver in the setting of type 2 diabetes

as i mentioned can lead to inflammation

or nash and liver damage and scarring

and when you look at people that have

type 2 diabetes they're more and and

they also have nafld they're more likely

to have nash so this liver inflammation

they're more likely to have liver

scarring and they're more likely to

progress to liver advanced liver

scarring so cirrhosis

and and and and also to develop liver

cancer

next slide

so what's so in the flipping it around

what's the link between nafl for having

fatty liver disease and type 2 diabetes

well people who have nafl so on an

ultrasound they're shown to have fatty

liver they're they're more insulin

resistant than those that don't have not

and when you look at people that have

naffle

they are two to threefold more likely to

develop type two diabetes over the next

five years

than those that don't have napple even

if they're not overweight

and people with a higher uh levels of

fatty livers or more steatosis

they're even more likely to develop type

2 diabetes and so the more fat one has

in the liver the more likely they are to

develop type 2 diabetes over time

and that risk is increased even further

if they also have associated liver scar

so

as i think marianne alluded to and i

think that picture that showed that that

that individual with the complications

of of uh diabetes traditionally

the approach to

finding and managing that when people

with type 2 diabetes has really been one

of i don't see anything here

and and the reason why i think is

because there was um

i think very limited understanding of it

i think there was a perception that it

was a benign thing that that would come

and go and didn't really uh drive any

sort of adverse liver uh outcomes

uh and and so it

was i i it was traditionally ignored

next slide

so so what's the real uh what's the

reality

uh is it that that we're making a big

thing out of nothing and and this is

actually just uh uh how we were managing

us in the past is the right way or is is

this

is this uh the zombie apocalypse and and

uh and this is something that's that

that that is that uh is a crisis

next slide

so

so when one looks at liver disease this

is this kind of shows what the liver on

the left is a normal liver that's f zero

means no scarring and as you go to the

right that's what is a liver specialist

what i'm most concerned about is you you

start to develop scarring in the liver

and when you get to f4 that's cirrhosis

when you get cirrhosis then you're much

more likely to develop liver cancer or

develop liver failure

and when you look at the drivers that

move people from the left to the right

type 2 diabetes is one of the key

drivers of that of that scarring in the

liver and that progression

and and that when you get that liver

fibrosis that's a key driver of poor

outcomes

so the question is if 45 to 75 of people

with type 2 diabetes have fatty liver or

nafl

how do we actually find those with

significant liver scarring so they can

they

that may benefit from seeing a liver

specialist recognizing what marianne

said was that most people are going to

have these other issues which are are

the things that are going to impact

their their lives more than fatty liver

disease well except the people that have

significant liver fibrosis

next slide

and so

one of the things we need to get better

at and and

and this is something where i think uh

uh people who manage individuals with

diabetes and people who who manage liver

disease especially

starting at a primary care family doctor

level is we need to develop and use

clinical care pathways

and case finding strategies so that we

can we can we can look at a at a large

group of people that have type 2

diabetes that are out in the community

seeing their family doctors and make

sure that the people with

nafld uh are are streamed in the most

appropriate care streams and usually

that will not involve the liver

specialist you know while someone's

helping to manage their their

cholesterol better their sugars better

and things like that because most of

them will not have significant liver

disease

excellent

and and i just want to highlight one

pathway that we developed in calgary and

through this pathway

that is really run by the family

physicians in calgary

is

we've been able to to you to funnel

individuals that are found to have fatty

livers some will have type 2 many but

happen of having type 2 diabetes and

another sort of 20 percent have are

pre-diabetic

we're able to funnel those

in to see a liver specialist if they're

found to have significant liver scarring

based on some very

sort of tests that can be done within

primary care and so it ends up that over

90 of the people that have fatty liver

never need to see a family a a liver

specialist as part of this pathway

next slide

so i'm going to

jump back a little bit to what do type 2

diabetes and what

how we we approach it and what our goals

are

so

with obesity

and um

and sedentary life being a huge

component a huge risk factor

for developing type 2 diabetes lifestyle

modification is number one in terms of

um treatment so we encourage people to

be active

to make sure that they're making good

dietary choices and i'll get into a

little bit more

um and hopefully with those lifestyle

modifications there'll be some weight

loss

and in people that we're not able to

achieve are to improve uh blood sugar

levels with either of those then we

consider medical therapy

there's oral medications there's

injectable medications and then there's

insulin therapy and i'll go into a

little bit more about each of these

next slide

so lifestyle modification

um and on the next slide i have a little

bit more detail um but it really is

about

um

making good dietary choices and people

patients will often ask me well what

what diet do you recommend what should i

be doing

we really encourage our patients to

follow the eating well um with canada's

food guide so a balanced diet and

everything in moderation

um

is there one diet that's better than

another really difficult to say

i often will tell my patients it's

whatever diet or whatever food plan

because diet also to me sometimes

implies that it's going to be a

short-term um

a short-term thing and that they can go

back eventually to their their their old

eating habits so whatever food plan they

can they can stick with and keep with i

think is going to be the most important

and the most successful

um in people who are overweight or or um

obese we do um recommend a nutritionally

balanced calorie reduced diet or food

plan um so that they do um lose weight

and then an intensive

behavior program maybe combining dietary

modification with increased activity and

what does increased activity mean so the

the um for diabetes canada recommends a

minimum of 150 minutes of moderate to

vigorous activity each week and and that

should be spread out over at least three

days so going out and doing a two-hour

walk one day of the week is really not

the the ideal um recommendation or

suggestion

ideally it's spread out over three days

and no more than two days without

exercise it's also important to really

reduce our i know it's hard in covert

times where everybody's working from

home and and i'm doing

a lot of online

meetings and things like that but it is

really important to avoid long periods

of time um

being sedentary so again to you know be

active for 30 minutes a day and then to

sit for the rest of the day is not the

ideal um situation so really important

to be as active um throughout the day as

possible and maybe breaking that up into

10 minutes three times a day which can

again be challenging but is probably

going to be more beneficial than just

clumping it to all at the starter at the

end of the day

um

resistance training is also um important

and it's recommended at least twice a

week preferably three times a week

in addition to the aerobic exercise

so really trying to be as active as

possible

next slide

and so in patients that aren't able to

control blood sugars with diet and

lifestyle and exercise we have we do we

do um uh treat them with uh

a very a

variety of different uh oral medications

um to start and and the order of how we

start this is really um gonna be

dependent on what else um what other

complications the patient has and we are

really

shifting towards a more patient-specific

regimen so i'm not going to really go

into too much about

when would we start this or when would

we start that but in terms of

medications that we have we have

medications like metformin that enhance

insulin sensitivity so they make the

liver more sensitive to the insulin

that's circulating so that the body

doesn't need to produce more insulin

that the insulin circulating

will be better recognized and function

better we have a medication like a

carbos that actually inhibits uptake of

glucose from the gut

um we have other medications like

secretogs that actually cause the body

to make more insulin um and then then

that insulin subsequently um works on

the liver to cause

and other tissues to cause the body to

um to use the glucose that's circulating

we have a newer class of oral

medications and injectables some of them

are injectable some of them are orals um

they're called incretin hormones and

these these medications work at the

level of the gut

and they

cause the body to actually

um create more of

jlp one hormone that is then circular

that then circulates and has other

effects outside of the gut and

specifically on the pancreas i'll get

into a bit more detail about that um to

help the pancreas um produce more more

insulin

um we also have a new group of

medications called sglt2 inhibitors

and again these these work differently

than all our other medications in that

they reduce the glucose reabsorption of

the level of kidney and cause the body

to excrete excess glucose

some older medications um called tzds

and these are

these are since uh also insulin

sensitizer not used very often these

days because there's been some concern

over cardiovascular

risks increased cardiovascular risks and

when all of these fail then often we'll

start to add insulin

and then again that just causes the body

to try and store

more of that circulating glucose

what's unique about these newer

medications so the sglt2 inhibitors as

well as the glp1 agonists is that they

actually lead to weight loss the sglt2

inhibitors will actually

prevent the reabsorption of glucose at

the level of the kidneys so you're

getting um

a loss of calories through

the kidney and urine this leads to

decreased fasting glucose levels

patients are more

less likely to have a rise in glucose

levels after a meal

their overall a1c which is our

long-term measurement of blood sugar

control is decreased suggesting better

blood sugar control they've also been

shown to have cardiovascular benefit and

not going to get into too much detail

there but important um in when we're

we're also talking about

um

nafld because we know with baffle

there's also increased cardiovascular

risk but these have increased

cardiovascular benefit and perhaps with

the weight loss that comes along with

this

is there a benefit on the liver

we don't know more more studies are

needed but there is the potential that

unlike some of their other older

medications that are causing the liver

to store more

um and perhaps maybe it

potentially could be exacerbating some

of the liver steatosis perhaps these

might actually have a benefit

glp-1 agonists as i started to mention

earlier

work differently than all our other

medications as well in that they work to

increase a hormone in the gut called

glp1

this hormone has a variety of different

effects

locally it causes a decrease in gastric

emptying so people feel full longer they

have increased satiety

it also works at the level of the brain

for to um

improve satiety as well so people feel

that they're more satisfied with less

food so tend to eat less

it works um

also at the level of the pancreas in

that it um increases insulin secretion

it decreases glucagon secretion so it's

causing the pancreas to work more

effectively more insulin circulating

helps to better control blood glucose

levels it helps with those beta cells so

those beta cells that are producing

insulin it causes an increased number of

beta cells it prevents beta cells from

dying off

it decreases

increases glucose uptake i think and

like the sglt2 inhibitors there's been

studies that have shown increased cardio

vascular protection

we know that weight loss comes along

with this

and potentially with all of these

benefits

uh improvements overall in uh liver

stantosis and i'm going to let mark talk

a little bit more about that but there's

been some preliminary studies that have

showed that

and it's definitely encouraging and

game-changing when we're thinking about

how we manage diabetes

one of the other benefits of both of

these medications is just that

often we're able to

use these medications and either get

patients off insulin or at least reduce

the amount of insulin that they're

taking and decreasing the amount of

insulin that they're taking is also

overall beneficial in terms of weight

loss and in terms of um the liver

and i'll hand it back over to mark now

thanks so thanks marianne so i'm going

to switch the management now just to

focus

as a liver specialist so i often focus

uh more on the on the liver which of

course you can see how these interact

and we need to have multi-disciplinary

approaches uh but the the the mainstay

of treatment is really quite similar to

treating type 2 diabetes is lifestyle

modification and targeting components of

the metabolic syndrome so obesity

hypertension hyperlipidemia next slide

uh and and when even though as a liver

specialist i have a tendency to focus on

on on the liver it's really important to

recognize that the liver

is not the biggest source of of

mortality or death in individuals with

type 2 diabetes it's

the complications that really mariam was

talking about so it's very important to

have optimal control of diabetes uh

control the high cholesterol and

triglycerides to treat high blood

pressure and then to do uh weight loss

strategies which include low

carbohydrate diets uh and the keto diets

the big one nowadays and uh low uh low

fructose so fructose is the main

sweetener in pot and pop is a huge

driver because humans don't metabolize

fructose and so it drives fat

into the liver which drives inflammation

next slide

i just want to uh there's a lot of

discussion these days about about the

mediterranean diet and i i think this is

quite relevant but here because as

marianne said i think the most important

thing is to find it's not a diet it's

it's it's a it's a it's a it's how you

like to eat that that suits you so you

can actually eat a healthy diet uh but

for when one's talking about uh weight

reduction in in the setting of nafld

you're really looking at about seven to

ten percent to start to really see the

beneficial effects on the liver and

around 10 percent to start to see

beneficial

beneficial effects with regards to

scarring

seventy percent seven percent to see

beneficial effects with regards to

inflammation and again there's a really

low carbohydrate low fat

or or different types of fat and so

vegetable not vegetables olive oil is

really a big driver of the mediterranean

diet and again reduced fructose

and the things that are listed here

under the mediterranean diet part fish

vegetables uh low sugar high fiber i

just also want to uh uh put it out there

that that there's a

growing epidemiological evidence that

coffee drinking is actually beneficial

from the for the liver point of view and

so if if i if patients come to me and

they're drinking coffee i actually

suggest they're even drinking more if

they if they can uh the important thing

is to recognize that if you're drinking

coffee and adding sugar like a double

double at tim hortons then that is

that's not actually drinking coffee

that's drinking sugar with cream and a

bit of coffee flavoring and so it's

really important to

to if you're going to drink coffee and

get the beneficial effect from it and

you should use non-sugar sweeteners and

try to use a low-fat

next slide

so what are the future farmer future

pharmacological therapies for for this

inflammation and scarring in the liver

associated with nap

well i just put this slide up to just

show you that there's a ton of therapies

out there in fact there's like

almost 800 clinical trials going on

across the world now for fatty liver

disease because this is such a huge

issue and they mainly target things uh

these different categories metabolic

anti-fibrotic anti-inflammatory i'm just

going to focus on two that i think are

relevant because they're the furthest

along and i think probably the most

exciting right now next slide

so what what are these liver directed

pharmacotherapies for patients with

nafld and nash the majority of whom are

going to have type 2 diabetes or insulin

insensitivity

next slide

so the first one is this drug called a

beta tocolic acid

and it's actually it's a bile acid

derivative and so our we have in our

bile is

in our bodies that we have bile acids

and they and they can stimulate a

receptor in our intestine called the fxr

receptor and this is a study that looked

at it over 72 weeks and what they found

with this so this is placebo in the blue

and then when you go to low dose and

sorry in the green the the low dose in

blue and the uh and the higher dose and

the pinkish color you can see in the top

bar that that there's an improvement in

in in scarring in the liver so fibrosis

is scarring and this is a one-stage

improvement so you can see that there's

actually this drug improves scarring in

the liver but interestingly if you look

at the bottom picture or bottom graph it

doesn't seem to change the inflammatory

component so they it shows us that

there's a differentiation between

impacting the inflammatory component

versus scarring and we don't understand

that very well at all

and it's relevant to the next slide

which is this this uh this drug that

marianne was talking about uh

semiglutids is a glp-1 agonist and

it's available to treat type 2 diabetes

and if you look on the on the left side

this is again treating with 72 weeks the

higher dose of semi glutathione 0.4

milligrams uh was significantly better

than the placebo in the in the gray bar

at

at making the inflammation in the liver

get better

however when you look in the right side

here it didn't seem to make any

difference with regards to liver

scarring

so again the they seem to be separate

and so the question about about these

type of drugs are do they impact if they

impact inflammation over enough time

maybe 72 weeks isn't enough time do they

actually also have a beneficial effect

on the scarring which is really what

we're most concerned about next slide

and that and i think that's that's

really the end of

what i have to say i think marianne as

well and uh

we're happy to take any questions and uh

answer any of your thoughts or comments

well thanks so much to both of you i'm i

can speak personally at least as someone

who lives with type 1 diabetes you know

i'm fascinated and it's it's not

something that i've been exposed to as a

complication or a comorbidity and it's

it's just really fascinating to learn

uh more about all these these

interconnections um so we do have quite

a number of questions we'll try to uh

tackle all of them um thanks everyone

for submitting your questions and being

curious uh while watching so the first

is

um

and and to answer folks just if you if

you feel that you have something you

would like to add just feel free to to

dive in we'll do a bit of a free-for-all

recognizing we just have the the two of

you so first question is uh how is nafld

diagnosed and how do you find out if you

have it or not so i think some probably

just looking for a bit of a

kick start or that first step of getting

a diagnosis

so traditionally uh

fatty liver actually was often not

diagnosed but nowadays i think if you if

you take people that have risk factors

for fatty liver and and the biggest risk

factors of course are are overweight

obesity and

type 2 diabetes or pre-diabetes and

but also people that have high

cholesterol or triglycerides those are

the people that are the highest risk

and

the probably the simplest way to

diagnose is if someone has an ultrasound

that shows fat in the liver that's fatty

liver

whether the liver tests are abnormal or

not

aryan do you have anything to add to

that

no not really i mean from a diet from an

endocrinologist perspective i will do i

will order um liver enzymes um on

patients if they're normal it doesn't

rule it out

but if it if they are elevated um i may

refer them on to um a hepatologist for

further investigation or for an

ultrasound

the interesting thing is in our in our

pathway in calgary we found that about

50 percent of people had persistently

normal liver tests that had fatty liver

that went back

over two years previous

and that the abnormal liver test did not

correlate with how much scarring they

ended up having in their

liver okay so we're we're learning a lot

about how to approach the uh

approach these patients i think there's

so much more that we need to understand

about how how to manage patients in a

way that really funnels them to the

right people because usually the right

person is not me

the next question is to do a little bit

with genetics which was alluded to you

know number of times as a potential risk

factor

the question is so here's a big one i

myself am type 1 my mom is type 2 and

has been diagnosed with fatty liver

disease that led to cirrhosis

does that then increase my risk

that's a very good question i don't have

a very good answer for that but but i

mean there are two different diseases

right that one's an autoimmune disease

and and although you can be a type 1

diabetic and also get insulin

you can also develop incidence and

insensitivity if you start to become

overweight and have those issues so you

can have this mixed pattern of kind of

like type two type one

uh and marianne would be the expert in

that uh but uh the uh um

i i don't think that

yeah

everything else considered that does not

would not place someone having type one

diabetes is of having the same

complications that

her mom had

yeah i would agree i mean i think that

you definitely can have uh

you can have type 1 diabetes with type 2

superimposed and we do see it we see

bariatric patients that have

type 1 diabetes and

requiring high high insulin

doses and post surgery aren't needing

the same type of insulin amounts post

bariatric surgery

so definitely it does does

occur

but are you at the same risk

if you don't have those other risk

factors i don't think so

have someone else who's wondering how

this topic relates to quote unquote

leaky liver

i have no clue because i don't even know

what leaky liver is but

when people get when people get

hyperglycemia so increased blood sugar

levels in the blood sugar levels

and they have nash so they don't but

they don't necessarily have to have

fatty liver uh it changes how the how

the cells that line the gut uh form a

barrier so normally our the cells that

line our gut are very good barrier for

bugs and products from bugs to getting

through that are really not good for us

and so what happens is that when you get

fatty liver or you get high like type 2

diabetes with high levels of of sugar

and you start to get an inflammation in

your body which goes along with that

it affects how how that barrier

functions so that it becomes leakier and

so and this felt to be that leakiness

can drive more inflammation in the body

which is which drives all of those uh

complicate many of those complications

that that marianne showed actually and

also drives worst liver disease

yeah we don't talk about

inflammation

often as part of one of the risk factors

but i think that there is

a significant amount of inflammation

that's happening that does lead to

increased insulin resistance whether

it's at the level of the gut um

definitely it was one of the of the

thoughts when i or

it is one of the thoughts with

infectious liver disease that the

chronic inflammation associated with

that increases insulin resistance and

leads to

increased risk of diabetes and there

have been cases where

you

treat their liver to treat their um

underlying infectious disease liver

disease so their hepatitis c and their

insulin needs actually improve because

there's decreased inflam with the

thought is decreased inflammation it's

not exactly well known but that's the

thought

um this next question is is probably

specific to mark and it's to do with the

the graphic you showed of the sort of

changing in color and

structure of the liver and it's someone

wondering can you can you fix the liver

and revert it to a nice pink one uh or

will it forever be damaged so that

that's a great question and uh

and so

the the liver is a fascinating organ in

that you can take a normal liver and

chop it in half and it grows back and so

it's the only organ that we have in our

body that regenerates so if the liver is

given an opportunity it regenerates and

so if if you can remove the damage then

the liver can get better but also people

used to think that scarring was

permanent but now we know there's

something called remodeling which means

that if the if you take away the ongoing

damage and the liver is able to pull

that scar tissue out as long as it's not

super well formed and super tight as if

it's a loose scar tissue and we know

from other liver diseases including

people that have profound weight loss

with bariatric surgery and things like

that that people can go from essentially

a serotic liver

to a liver that looks normal

is is it totally normal it's probably

not totally normal because there are

some other issues that go along with it

and the predisposition to cancers and

things like that if they already had

cirrhosis so really bad scarring that

probably gets less but probably doesn't

go back down to normal but the function

all those kind of things

uh and the sort of the more pinkiness as

the as the fat leaves the liver because

it's the pink that's the the yellow is

the fat not and that's what's changing

the color of the liver it would go back

to pink yes

that's that's fascinating i i didn't

know that the liver was regenerative

yeah it's pretty amazing and so that

that's actually the basis behind a liver

relating donor so when people get a

liver trap let's say you have advanced

uh

you're unfortunately have developed a

liver failure because of say napoleon

and someone in your family or whatever

can donate part of your liver and when

that liver is put in your body that

liver grows right to the same size that

your liver was before and the person

that donated the liver that their liver

goes right back to their same size their

liver was in their body

it's quite fascinating

well it's a miracle action

um we have someone wondering uh if blood

sugars are controlled through

medications despite still having sweets

is there a negative impact to the liver

in other words is it the level of sugar

consumed or the amount of sugar the body

needs to deal with that is most

detrimental to the liver

well that's a very i'll let marianne

take that action yeah that's a

complicated complicated question with a

complicated answer um definitely i think

when if you're having increased um

simple sugars sweets etc your blood

sugars are going up and depending on

what treatment you're on assuming let's

say you're on insulin you're taking

using more insulin and basically you're

actually causing the body to store

more

uh and the liver to store more so

you it could potentially be harmful and

we don't know that and i think that's

one of the things that um is

is different with some of these newer

medications is that they don't cause the

body to store more they cause you either

to to consume less

or to get rid of that excess um

uh glucose through the kidneys um and so

perhaps in those cases it wouldn't so i

really think it depends on the type of

medication you're on

and and potentially but potentially it

could cause more um aggravation in um

inflammation within the liver and more

fat to be accumulated

there's a question to do with um asking

if liver disease could be under

diagnosed uh if liver enzymes may not be

affected as it seems like the ultrasound

is done to only confirm the disease

yeah so liberty we know it's under

diagnosed right and and yeah an

interesting thing i have a discussion

all the time because i think that if you

go to most endocrinology practices they

say i don't see much liberties like i

don't see much end-stage liver disease

there's cirrhosis and i think that's

because endocrinologists are very good

broadly at controlling people's blood

sugar and they and they're focused at it

and they're very good at it and so their

and their goals of human government a1c

are relatively tight and sugar control

is tight but when you move away from a

specialist who's dedicated with that

move into into more sort of i guess into

a more of a community center setting

often the the the range of sugars that

are allowable that are that are okay are

are broader and the hemoglobin a1c

levels are often higher and i think as

in those individuals that where where

we're more likely to see uh because we

know that progressive liver disease is

related to

glucose control essentially uh in type 2

diabetics and so uh i think that's where

we're we see a lot of individual more

individuals that are going to be

presenting with with end stage liberties

and i can tell you as a liver specialist

we're seeing

many more people present now with liver

failure liver cancers that are that are

being driven by fatty liver disease not

by the traditional things like like

infectious hepatitis that we normally

would have thought as the key driver

so folks i think we have time for

probably one more question then we'll

have to have to wrap up but there's

there's one that frankly i'm curious

about this as well and i'll direct it to

mark and it's

why is coffee good for liver disease

what's the uh do you know more about

that

well it's interesting

so

caffeine broadly is beneficial to the

liver in that in that in that caffeine

stimulates a certain type of receptor

that's very important for blood flow to

the liver and that so that probably is a

beneficial effect of that

but it's more than just the caffeine

because it's actually if you look at if

you look at say caffeinated drinks that

that are not coffee they actually

um

have they seem to have a benefit but not

the same degree of benefit

as coffee and in fact there is even some

evidence that certain

ways of making coffee like a drip coffee

seems to be better than an instant

coffee and

so there's a lot left to be learned but

uh but but certainly i think it's if

someone likes coffee

i i don't think there's a downside

unless they have a heart issue or a

rhythm issue in their heart drinking

more coffee as long as they're not

adding sugar to it

okay that is it is really interesting

i've uh i'd like to before we wrap up

just sincerely thank you both uh it's

been such an interesting conversation i

you know i personally i've learned a lot

and i hope the same is true for uh for

our viewers and to our viewers i'd also

just like to say if you have further

questions please feel free to

visit diabetes.ca or to contact us

directly at 1 800 banting or info

diabetes.ta

um

you know i just once again really

sincere thank you to dr doyle and dr

swain and uh i'll also hand it over to

them to provide any any more information

on the canadian liver foundation

oh absolutely thank you for that it's uh

absolutely a great great conversation

very stimulating there and uh again for

more information i think both

organizations provide uh

quite a hefty amount of our resources

and support um for more information on

liver disease and all of disease we have

our liver.ca website that contains

all the information about fatty liver

disease and all the associated liver

diseases that dr swain

was indicating and speaking about

broadly

and we have also our email that

all patients and caregivers and those

who want more information to reach us

it's at clf liver.ca but again liver.ca

for additional information

okay thank you and once again thank you

everyone for your time and for sharing

that information greatly appreciated and

take care of everyone okay thank you so

much and thanks marianne that was really

a joy uh presenting with you

thank you too mark i enjoyed it as well

it was great

bye folks thank you thanks