�DIABETES:� WHERE WE ARE TODAY, WHERE WE WILL BE TOMORROW

� by Frank Vinicor, MD,� MPH

Dr. Vinicor, director of the Division of Diabetes

Translation at the U.S. Centers for Disease Control, in

Atlanta, Georgia, gave the following as the keynote address

at the 1999 annual conference of the Diabetes Action Network

of the National Federation of the Blind.� The conference

took place on July 2, 1999, at the annual convention of the

National Federation of the Blind, in Atlanta, Georgia.

I have been here at Centers for Disease Control for

about ten years.� Prior to that time I was at Indiana

University School of Medicine.� I'm a card-carrying

endocrinologist and diabetologist.� I did clinical work and

clinical studies, and then went to the University of North

Carolina, to the School of Public Health and received a

masters in public health, and then I came to the CDC.� I

think many people are wondering why diabetes is studied at

the CDC.� It is because we do not just study the outbreak of

infectious diseases, like hanta virus or influenza, but

there's also a lot of activity at the CDC now in chronic

diseases.

In the United States, probably 70% of health problems

and their costs are related to chronic illnesses like heart

disease and diabetes and the like and so there's a big

program, the Division of Diabetes Translation, to get all

those research findings out into regular practice.� It's no

longer good enough for people to do research and publish it

in the professional journals, and just wait for it to affect

medical practice.� Research that isn't applied in daily

practice is research that's wasted.� And so, our primary

responsibilities are to actively translate research into

practice--to take all those articles that appear, all the

funding research that NIH does, and at the CDC, translate

them into practice.� The public health part of what we do

falls into three main responsibilities:

First is to know something; such as how many people

have diabetes, how much it costs, what kind of health

problems people have.� We try to figure out the size of the

problem of diabetes.� Another thing we do at CDC is try to

know why things are the way they are.� For example, why

diabetes is much more common in Hispanic communities or

African American communities.� We know that African

Americans, for example, once they have diabetes, have more

problems with kidney failure.� We now need to know why that

is.� That makes us very different from NIH--because CDC has

a congressional mandate to do something.� It isn't just

enough to do the research, but once you have the answers,

there is a responsibility to develop programs that make a

difference.

We produce documents.� One that's very popular is

called Take Charge of Your Diabetes.� It's a very practical,

patient-oriented book, also available, from the National

Library Service for the Blind and Physically Handicapped, in

Braille and on audiocassette.� That's one example of what we

do.� There's a heck of a lot more that we can and should be

doing.

What I thought I'd do is initially cover four areas:

one is give you a sense of the size of the problem of

diabetes in the world, including the United States.� Then

talk in general terms about where we can make a difference.

What are our choices about where we can make a difference to

stop some of these problems of diabetes?� Then I'll talk

about some of the research directions that perhaps aren't

right there today, but soon will be.� Then I'll just pose

some challenges that I think exist for all of us in taking

on this thing called diabetes.

In terms of the problems of diabetes in the United

States, how many people have it?� How many people are going

to develop it?� What kind of problems they have?� How many

times do they go see those doctors?� What does it cost?

Whatever criteria you want to use, to decide if a problem is

a big problem, diabetes fits the bill.� If you want to think

about how common it is, diabetes, sixteen million people

have the condition.� About five million or so have it, and

don't know it.� Those are accurate figures, but, to me, that

number, "sixteen million," doesn't grab me in the gut.� It's

too big a number.� Another way to think about it is, between

when you woke up this morning and when you wake up tomorrow

morning, there will be slightly over 2000 Americans

diagnosed with diabetes, every day.� And that's going to

happen every day of the week.� It's going to happen on the

fourth of July, and it's going to happen on the weekends.

Every day there are going to be about 2000 more people

diagnosed with diabetes.� That's giving you some sense of

how common this is.

The complications of diabetes are also big, and

obviously you have been dealing and wrestling with the

visual problems.� Blindness, kidney failure, and amputations

are three of the big problems, as is heart disease.� Again,

let me give you a flavor of how common these problems are.

I know this sounds discouraging, but I think we have to get

a sense of where we are and where we're going, to appreciate

the importance of good research and good translation.� In

terms of kidney failure, again, between when you woke up

this morning and when you wake up next morning, about 70

people will experience kidney failure and will have entered

kidney failure programs, either going on dialysis, or

getting a kidney transplant.� In terms of amputations,

diabetes will cause, every day, between this morning and

tomorrow morning, 150 amputations, again, every day.� And

finally, in terms of legal blindness, about 75 people in

this country will go blind, every day, from diabetes.

That's a lot.� That gives you a flavor.

Every morning you wake up, it will have happened.� So

we're not dealing, obviously, with a rare, uncommon, or

benign disease.� And we're not dealing with a cheap disease.

Diabetes costs the country about a hundred billion dollars a

year.� What that means for the individual is, whatever the

average person, who doesn't have diabetes, pays for

healthcare, people with diabetes will pay three times that

much.� So, on average again (there are exceptions where

people are paying more or less), people with diabetes are

going to be paying roughly $10,000 a year for their care, or

somebody's going to pay for that.� Diabetes is incredibly

expensive.�

Now I realize that all of that is discouraging, but

I've got to stick with this, because I want to say that it's

not only discouraging in the United States, but it's

becoming very discouraging throughout the world.� In a study

that we did at the CDC with the World Health Organization,

we know that right now there are approximately 125 million

people with diabetes in the world.� By the year 2025, only

25 years from now, there will be 300 million people with

diabetes.� Most, almost all, of those people will be type 2.

The reasons why this explosion in the number of people with

diabetes are several.

Lifestyle is certainly one of them.� All of us are less

active and getting heavier.� In the United States, obesity,

improper nutrition, and increased television watching are

all epidemic.� So, one of them is our behaviors.� The second

one has to do with what are called demographics; changes in

the population.� Generally, people, even in developing

countries, are not dying of childhood diseases as much as

they used to.� And that's a wonderful accomplishment.

They're not dying of diarrhea, or dehydration, or measles,

or the like.� And so, on average, countries' populations are

getting older, so more people are reaching an age where

diabetes is more common. �Another factor is that in the

United States there are populations who are particularly

prone to get diabetes; we're talking about African

Americans, American Indians, Hispanics, Alaskan natives and

Pacific Islanders.� Those populations are growing at a rate

considerably higher than the white population, such that by

approximately 2050 AD, the minority populations would be, in

the aggregate (all of them together), about the same

percentage as the white population.� So another reason why

diabetes is growing, in terms of prevalence, how many people

have it now, is because those populations that really face a

greater challenge from diabetes are increasing at greater

number.� So we've got all our behaviors, and we've got these

demographic changes.

Also there's another major factor which accounts for

why we know that diabetes is going to be a bigger problem.

And it has to do with the word ascertainment, which means

accurately obtaining data.� Diabetes has always been a big

problem, but the systems that collect information on various

diseases haven't been collecting information on diabetes

very well.� For example, if you take 100 people who have

diabetes, and they know they have diabetes, and they're in

the health care system, the system knows they have diabetes,

and they die, only 40 of them will have diabetes listed

anywhere on their death certificate.� In terms of looking at

mortality, death, as an indicator of how bad a condition is,

we have been underestimating the contribution of diabetes to

that indicator of health.� Likewise, if you look at people

who have diabetes, they know they have diabetes, they're in

the hospital, and you look at the discharge summary, 40% of

those people will not have diabetes listed on the hospital

discharge summary--there'll be no record of the role their

diabetes played in putting them there.

That's all changing now.� Our systems of collecting

information are getting a lot better, and we're not missing

the problems of diabetes.� So when we put all those things

together, our general view about diabetes is that things are

going to get worse before they get better--in terms of the

number of people and the kind of problems.� Now, that's the

first part, and I know that's discouraging, but I wanted to

get it out of the way.� Because if you ask yourself:� Are we

locked into this scenario?� Is there nothing we can do today

about diabetes?� Is it inevitable that things are going to

get bad and it's going to happen like clockwork and there's

nothing we can do?� The answer is no, no, no, no and again,

no.� We are not "stuck."� There are things we can do today

for diabetes.

Let me just mention three general areas of what we can

do for diabetes today.� Let's talk about what we now call

type 2 diabetes.� We used to use the term "adult onset",

then we started using the term "non-insulin-dependent

diabetes" and now we use the term "type 2".� And what we're

talking about typically is the situation in which the

individual is "over, under, over".� Over forty, underactive,

overweight.

Type 2 probably accounts, in the United States, for

about 90% of diabetes.� We now know that for type 2 diabetes

that there may be an approximately ten-year time period, on

average, between when somebody develops type 2 diabetes and

when it is diagnosed clinically.� In other words, people

with type 2 diabetes will typically go, on average, one

decade with the condition, with the high blood sugar, and

the bad things that can happen with the high blood sugar, so

at time of the diagnosis of type 2, about a third of these

"new" diabetics will already have preventable complications

of diabetes.

One thing we can do to stop this from happening, is to

try to identify people earlier, before we clinically make

the diagnosis.� When the condition is present, but maybe

there aren't symptoms, or the symptoms don't suggest

diabetes, we need to have a good look.� For example, VOICE

editor Ed Bryant mentioned that he's 54.� I'm four years

older than he is, I'm 58.� If I woke up in the middle of the

night a couple of times and had excessive urination, I

probably wouldn't think first about diabetes.� I'd wonder

about my prostate gland.� Or, if for my age, I started

having some visual blurring, I probably wouldn't think about

diabetes, necessarily.� I might think about cataracts or

something like that, 'cause I'm getting up there in age.

So, even for people who have these symptoms of diabetes,

they don't necessarily know they ought to be tested for it.

So, one of the things that we're doing in the United States,

is trying to develop a reasonable early screening program.

One requires a simple blood test.� It's not expensive.� It's

not particularly painful.� Particularly, if you have

diabetes in your family, if you're overweight, if you're

from minority groups.� Trying to find diabetes earlier and

start treatment earlier to prevent the complications is one

thing that we all can do together.

The second thing that we can do together is to ensure

access.� I think it's an embarrassment in this country, that

when diabetes is discovered, many people still don't have

access to quality care.� And particularly at a time when

this country economically is doing very well, particularly

at a time when the unemployment rate is down to 3 1/2 to 4%,

particularly at a time when certain people are bringing in

huge amounts of money, the fact that the number of people

who are uninsured, who don't have financial coverage for

health care, is going up.� I just find that unacceptable.� I

personally think that's ethically unacceptable, from a

social justice standpoint.� So, I believe we need to ensure

that when people have their diabetes discovered, they in

fact get access to good care.� That's the second thing we

can do.

The third thing we can do is insure, once diabetes is

discovered, that you get care of appropriate quality.� Now

let me explain what I mean by that.� We now know, and have

good, excellent studies, solid scientific and economic

studies that show that if you control your blood sugar

pretty well, if you control your blood pressure pretty well,

and if you control your blood lipids, your blood fats,

pretty well, you do not have to go blind, develop kidney

failure, or develop heart disease.� We also know now that if

you have diabetes, and you find retinopathy, eye changes,

early, or if you find early kidney changes, such as a little

protein in the urine, or for example you use the little

monofilament to test your feet, this little plastic

monofilament that is very, very inexpensive, costs about 10

cents, and can be used repeatedly, that tells you if you

have what's called an insensate foot, a foot that's lost its

sensation; if you find that out, and you wear protective

shoeing, we now have studies that show you don't have to

have a foot ulcer or an amputation.

We don't need to "prove it."� We have the proof.� And

so what I'm saying is that quality of care is our most

potent weapon today to prevent those very things from

occurring.� I believe strongly that with good care we don't

need to see 75 people go blind every day, 70 people enter

kidney failure programs or 150 amputations a day.

The real challenge is to ensure that people get access

to quality care.� That's not an easy challenge, but with the

private sector and the public sector empowering people with

diabetes, all of that is coming together to make a

difference.� So even though I do believe that things are

going to get worse, I think we all contain the power to make

that period of getting worse short.�

With the knowledge we have today, we can move forward,

and make a difference.� But let me go on, and talk a little

bit about research.� I love reading the VOICE.� I'm glad Ed

keeps sending me a copy of it.� You all have your own

contacts, you all obviously are very energetic about your

interest in diabetes.� I've heard already here about your

awareness about the pumps and the non-invasive monitors.

You're currently on the cutting edge of this.� But let me

share my sense of the research area.

Now, if I see somebody, an individual with diabetes,

and I really want to do something to help that person, I've

only got three choices.� I could prevent diabetes.� That's

one choice.� The second choice is that once they have it I

could cure it.� And the third choice I have is to do the

best job that I can, to care for them.� So let me share with

you a little bit about what's going on in the research

field, in each of those categories.� What are we doing, what

do we know, where are we, in terms of trying to prevent

diabetes.� Where are we and what do we know and what do we

not know about trying to cure it, and then where are we in

trying to do a better job in caring for it.

So let's first talk about preventing diabetes.

Wouldn't it be great if we didn't have to worry about

diabetic retinopathy and blindness because we didn't develop

diabetes in the first place?� It'd be wonderful.� What do we

know about preventing type 1 diabetes?� We know a lot.� And

there are studies going on now to try to prevent type 1

diabetes.� I don't know about you, but when I was a young

man, which seems like years ago, in medical school, I was

always taught that the person with type 1 diabetes was

healthy on Tuesday, and on Wednesday was sick as could be.

That type 1 diabetes was a sudden-onset condition, that

would develop in 24 hours, and could be lethal unless you

got treatment for your acidosis.�

We don't think that anymore.� We now hold a completely

different view of type 1 diabetes.� We know that as many as

10 to 15 years before the clinical onset of type 1, for

whatever reason, the body starts to see its own insulin-

producing cells as foreign, "not mine," and starts setting

up an immune destructive response, one that goes on and on

and on and destroys the insulin-producing beta cells.

Eventually it kills off enough of the one million beta cells

we have in our body that you develop type 1 diabetes.� That

process can take 10 years.� Furthermore, we know that by

doing certain genetic studies, you can identify people who

are at risk for this condition, and further, if you do

measurements of proteins in the body that are directed

against the insulin producing cells, you can actually

predict very accurately who, within a year or two, will

develop type 1 diabetes, unless something is done.� That's

all new information in the last five to 10 years.�

There are now three major studies identifying people

who have this genetic marker; people who have these

antibodies present, directed against their own insulin

producing cells.� Now they don't have diabetes, their blood

sugars are normal--but these three major studies are trying

to stop the immune destruction, to try to stop that sort of

self-destructive process in the person's own body that is

the onset of type 1 diabetes.� One of the studies is called

"The Diabetes Prevention Trial Type 1."� It's going on in

the United States.� The second study is called E.N.D.I.T.,

the "European Nicotinamide Diabetes Intervention Trial."� In

this, researchers are giving this compound nicotinamide to

people at risk for developing type 1 diabetes, to try to

stop the destructive super-oxygenation that goes on when the

Beta cells are attacked.� And the third study, just coming

out of Scandinavia, is called the TRIGGER Study.� The

important point is that these big multi-center studies will

probably come up with some answers, by 2002 or 2003, as to

whether or not we can prevent type 1 diabetes.

What about type 2 diabetes?� All of us know that type 2

diabetes occurs in people who are "over, under, over."� What

happens if we can find people who are at risk for type 2

diabetes?� What we look for is people who have what we call

impaired glucose tolerance.� If you test their blood sugars,

their values aren't yet in the diabetes range, but they're

above normal.� Can we stop those people from getting more

"over, under, over?"� We can't do much about their age, but

the underactive or overweight?� What if we can do something

about those two?� Right now there are two or three studies,

the biggest one, being the Diabetes Prevention Program Type

2, in which about 6000 people identified with impaired

glucose tolerance are being randomly assigned to either

continue very mild activity or behavioral interventions or

also to receive the oral medication Metformin.� Now these

folks don't have diabetes, but the idea is to see whether

development of diabetes can be stopped, to prevent type 2

diabetes.� That study is going on at many locations.� Its a

25-center study,� and those results will also be out in

about the year 2002.

So current research has gone beyond basic

understanding, test tube research, etc., to intervention

trials.� It may mean that by the time you meet three years

from now there'll be exciting news about whether type 1 or

type 2 diabetes can be prevented.�

There are now increasing amounts of type 2 diabetes in

children.� Most of us have been trained to think about type

2 diabetes as "over, under, over", over 40, underactive,

overweight.� And if I told you I had someone who was 14

years old and had diabetes, you might automatically think

that person had type 1 diabetes.� Particularly in minority

communities, there are now a number of case series in which

youngsters most often in their 15, 16, 17 year age range

have full-blown classical type 2 diabetes.� Particularly

American Indians, African-Americans and Hispanics, but cases

are now also being reported in white communities.� Almost

always this condition is associated with being overweight

and underactive...� Interestingly enough, there is often a

very unusual skin condition, called Acathosis nigricans,

associated with it.� "Acathosis" means a thickened, velvety

skin on the back of the neck and "nigricans" means dark.� So

it's a darkened, thickened, velvety skin on the back of the

neck, in the armpits, etc., associated with this juvenile

type 2 upsurge.� For all the world, it is type 2 diabetes,

as best we can tell--and it is occurring at age 15 years.

What does that mean?� Well, it's really scary, because what

it means is that normally we think of type 2 diabetes on

average occurring at age 50, and we are wrestling with what

it means to have type 2 diabetes for 30 years.� Well, are we

gonna have to start asking the question:� "What does it mean

to have type 2 diabetes for 60 years?"

Right now there are several projects addressing type 2

diabetes in youth.� One is through the CDC, to document the

existence of this on a population basis.� Another on July 20

and 21, a conference at NIH, will look at some of the basic

biomedical and biological reasons why this might be

happening.� The ADA has just issued a position paper.

Everybody is aware of, interested in, and frightened by this

phenomenon.

Now let's go on to the next area.� Where do we stand

with cures?� The whole understanding of curing diabetes has

changed in my lifetime.� If the problem of type 1 diabetes

is just losing your insulin-producing cells, why can't we

just replace those?� There are four different types of

studies going on for "curing" type 1 diabetes.� Number one

is transplanting the pancreas.� The pancreas is a strange

organ.� Most of the pancreas is there not to prevent

diabetes, but to help us digest food.� All the enzymes in

your stomach and your intestines come out of the pancreas,

and in fact the insulin producing cells represent about .01%

of the pancreas, a very small percentage.� But, if we can

transplant hearts and kidneys, why can't we transplant a

pancreas?� It's tricky, because it's located way in the back

of the abdominal cavity, in front of your spine.

They do now transplant pancreases--not the whole thing

but what's called the Segment Transplant where if someone,

for example, has died in an auto or motorcycle accident,

they can remove the pancreas, a part of it, and transplant

that.� There have� been about, throughout the world, maybe

10,000 or 12,000, pancreas transplants.� Again, it's not

your pancreas so you're gonna have to take some drugs to

prevent rejection.� But some people have had a remarkably

successful experience.

Doctors have actually been doing the whole pancreas

transplants in some centers, like University of Minnesota,

for 10-15 years.� A number of people have lived that long.

A larger number of people have been transplanted in the last

three to five years, and generally it's been quite

successful, both certainly in terms of people surviving, and

also in terms of the pancreas transplant functioning well.

What's the success ratio?� This we define in two ways.� The

most basic is, did the individual live?� And the second one

is, did the transplanted pancreas live?� And for the

individual, you go out three, four, five years, probably 95%

of the people are still alive.� So the success of the

pancreas transplant depends on how you define the word.� If

you define that as going completely off insulin, that's a

pretty rigorous definition.� Generally speaking, the

pancreases seem to work three to five years out, in the

range of 70-80%.� It's a pretty high success rate as things

go.

Who is eligible for a pancreas transplant?� In general,

the criteria are that� if you need a kidney transplant, and

you're going to be exposed to immunosuppressive medications,

lets go ahead and try to do a pancreas transplant at the

same time.� There's a little bit of "opening up" now; some

people now are just having a pancreas transplant.� If you

have a kidney and a pancreas transplant, Medicare has just

decided they would pay for that.

The likelihood of rejection, that the body will reject

the new foreign organ, is about the same for a pancreas as

it is for a kidney.� There are a lot of new, less toxic,

medications coming out to prevent rejection, and that's

encouraging.���

A person with a kidney transplant, already taking

immunosuppressants, might well be eligible.� It depends on

individual circumstances.�

There was a question about diabetic coma and its effect

on transplants.� There are three types of diabetic coma.

One is when you have what's called acidosis which for type 1

is where the pH number, the measure of acid in your body,

gets so low that you can go into coma.� There's another kind

of coma, where the blood sugar gets so high, that in the

absence of acidosis you can go into coma.� And then there is

the low blood sugar coma.� Those don't really affect the

success of transplantation, in and of themselves.

Let me go on and tell you about three other choices

that we might have in the near future.� I spoke about

transplanting a chunk of the pancreas, like half of it.

Another choice we have, since I said the insulin-producing

cells make up such a small amount of the pancreas, like

.01%, is to get just the insulin producing cells.� What

we're talking about is Islet Cell Transplantation.� It is

possible now to collect those, such that you can sort of

slice up the donated pancreas, and quickly and pretty easily

collect those.� It turns out that you don't need a million

insulin producing cells--to not get diabetes, you need a lot

less.� Somebody was smart, and put in some reserve, I guess.

You probably need 100,000, maybe 200,000 at most, to get

away from diabetes and you can get those cells.� A number of

centers are doing studies, not� transplanting the whole

pancreas, but the islets, the insulin-producing cells

themselves.

The new islets are injected into a vein, with a regular

syringe.� Most often they go into the liver and set up

housekeeping there.� It's technically not a big deal, but

the body is just so darn smart, so much smarter than we are.

It even knows about these little cells, and the body's smart

enough to say, "they ain't mine."� The body again will try

to reject these.

There are a couple of ways people are trying to stop

this rejection.� One of them is to again give various

immunosuppressant drugs, just like you do for kidney

transplant or whatever.� Again, the drugs are getting

better; they're getting less toxic, more effective.� Another

tack they're trying is to use engineering techniques.� They

put these little insulin producing cells inside something

like a straw, a small straw, with small holes, big enough to

let sugar come in and insulin come out.� But the holes are

too small to let the destructive proteins, or the white

blood cells, get in at them.� Just two or three weeks ago,

the National Institutes of Health made a decision to devote

$125 million to a project to do clinical trials on islet

cell transplantation.� That means moving along, outside of

the laboratories.

Because of the location of the pancreas, and because

you only have one, at this point in time new islet cells

must come from cadavers only.� Now there are studies going

that are looking at fetal islet cells, but that raises a lot

of ethical questions, about abortion and studying fetuses.

But fetal islets are viewed as less formed; some people are

doing studies on transplanting pig islets, because pig

insulin is only different from human insulin by one little

amino acid.� So what works right now is cadaver transplants-

-but this second way of just transplanting the islets is now

going to be big time with this $125 million.

The clinical trial just started; they just made the

decision last week.� There'll be advertisements coming out

about 800 numbers to call.� A lot of information will be

published shortly.

I mentioned about the whole pancreas.� I talked about

the islets.� We're pretty smart.� I mean we can send people

to the moon and all that kind of stuff... Why can't we make

an artificial pancreas?� In fact, we can make two out of the

three parts really well, and we've been able to do that for

ten years.� We know how to make a little reservoir to store

insulin right below the skin.� That's a piece of cake.� We

know how to make pumps to squirt out insulin.� A lot of

people have been doing that for years.� The third necessary

part, which we are really struggling with,� is that

interactive sugar sensor.� To get a glucose sensor, a sugar

sensor, that will last more than a few days, and will give

us accurate readings, there is much effort in the private

sector.� Pump manufacturer MiniMed just got FDA approval to

do some work with their sensor.� All of that is so exciting

in terms of completing the third of the three parts.

Right now, if you wanted an artificial pancreas, some

exist in experimental units.� They probably weigh about 200

pounds.� You could carry that on your back, you know, like a

backpack and walk around.� But the first two parts, the

insulin reservoir and the pump, they've been miniaturized,

they're failsafe.� No big deal.� But until we can get that

glucose sensor thing worked out (and they've made a lot of

strides), we're not going to be able to do that.� I predict

that within two years there will be a reliable group of

sensors that will last for a long time.� And then we'll have

this artificial pancreas that may be the size of a cassette

player or something.� It'll probably be ultimately internal,

"internal" being right below the skin.

Why do we have to depend on islet cells?� I mentioned

that they're hard to get.� The pancreas is way in the back

of the belly.� It is a pain to get at it.� But we do genetic

research today.� Most of the insulin that you're using (if

you inject) isn't produced by a human.� We've tricked some

bacteria into making human insulin.� Why can't we trick fat

cells, for example, or muscle cells, to make human insulin.

Why can't we take the human insulin gene and insert it into

a human cell, and have it produce human insulin?� This

fourth source of insulin replacement would be to take non-

insulin-producing cells, insert the insulin gene, have it

produce insulin, and then inject those cells into the body.

You could take somebody's own fat cells and do that, and re-

inject it, and not have to worry so much about rejection,

itself, because it's their own fat cells.� They can do that

now; they have the techniques to do that.� The challenge is

to be sure those fat cells, or muscle cells that have been

tricked into producing insulin, turn off the insulin release

when it should be off and turn it on when it should go on.

We don't want those cells suddenly putting out a whole bunch

of insulin, when in fact, my blood sugar is 40.� And we do

want it to produce insulin if our blood sugar is starting to

sneak up.� And that's the part that still hasn't been worked

out yet.� We can make those cells produce insulin, but, are

they sensitive, like our Beta cells?� That's the next

challenge.� But within three to four years we're going to

have more choices on curing type 1 diabetes.� Pancreas

transplant, islet cell transplant, artificial pancreas, and

"tricked fat cells."

Some of you have questions about non-invasive blood

glucose monitoring, and about the Glucowatch monitoring

system.� There are five or ten different approaches� people

are exploring, to measure sugar without having to prick the

finger, or do a blood test.� One of them is on the skin,

where the idea is that, in essence, the skin juices, like

sweat, will change as your blood glucose changes, and that

would give you some indication of the sugar.� Another

technique actually uses a Laser beam that literally, blows a

small hole in your skin.� And there are other techniques.

What about the new developments with inhaled insulin?

We know that we have to take injections.� The needles and

syringes have gotten smaller, better, sharper.� We've got

the pen.� We've got pumps.� There have been a number of

studies done to look at how insulin could be administered,

other than by subcutaneous injection.� One was through the

nose, a nasal spray.� Another was through a rectal

suppository, but� I don't see a lot of enthusiasm for that,

even though it worked.� And recently, there have been two or

three studies about inhaled insulin.� In other words,

insulin is aerosolized, and it gets down into the lungs; way

down deep into the lungs.� The initial studies with both

type 1 and type 2 diabetes have been very, very positive, in

terms of the body's ability to absorb insulin; very, very

positive in terms of the ability to control blood sugar, but

the concentration that you need to have there is quite a bit

higher than� U100.� U100 means 100 units per CC; the

concentration is quite a bit higher than that.� But the

studies have been so exciting and so positive that all of

the major insulin producing companies, Lilly, Hoechst,

European companies, etc, have an active program on

developing inhaled insulin.� They are now going into other

studies, what are called Phase II and Phase III trials,

where the number of people involved is greater, where

they're looking to see what's the effect if I have a cold or

bronchitis, does that change the absorption of insulin, for

example.�

The initial results are very encouraging.� The study

subjects love it.� I suspect within a year or two, you'll

see major studies, and probably within three years or so

you'll begin to see some availability.� I don't suspect it

will be available to everybody, as there are very practical

issues to work out, like if the absorption doubles when you

go to a humid zone, you probably need to know that, so you

don't have a hypo...� But, the initial experiments are very

positive.�

Let's go on and talk a little bit about caring.� I

mentioned preventing and curing�� Let's talk about caring.

Where are we now with "caring?"� Well, we've come a long

way.� I've been in diabetes now for about 30 years, in terms

of my professional life.� I don't have diabetes myself.� And

I think as bad as it is to get diabetes today, July 2, 1999,

it is so much better than it was to get diabetes ten years

ago, let alone 20 or 30 years ago.� We have better, purer,

more varied forms of insulin.� We now have four, and soon

we'll have six or seven types of oral tablets to take.� We

now have better meters, they're smaller and cheaper and more

accurate; strips still cost way too much.

But we've got better meters.� We now have a way to

ensure that you're not fibbing me when you come in to see

me.� Everybody who comes in to see me in my office�� when I

do a blood sugar test when they're there to see me, it's

beautiful.� And, right before, they stop eating the cake and

they start to exercise...

We now have this test that has dramatically changed our

understanding of long term control of diabetes, the A1c or

glycosylated hemoglobin test.� That's a major improvement in

our ability to care.� The A1c does not show peaks and

valleys, but averages.� The A1c will give you your overall

average blood glucose to help you and your doctor or your

nurse to see how you've been doing.�

We now have better ways, for example, to detect kidney

disease.� We now know that well before kidney tests indicate

kidney diseases, for both type 1 and type 2,� if we look at

the urine and detect small amounts of protein in the urine,

micro-albumin, we now know that's a sign of very, very early

kidney problems.� And we further know that if we use certain

medicines to lower the blood pressure, or to treat that

protein, the ACE Inhibitors, we know we can substantially

prevent the development of kidney failure, regardless of

what the blood sugar is.� And if you put those two things

together, you control the blood sugar, the blood pressure,

and take this medicine to stop the protein, you really can

prevent kidney failure.

What about the side effects of the ACE Inhibitors?

With any medicines there are certain side effects.� Some of

them are mild and some of them are severe, but most of them

are infrequent.� For example, with any blood pressure

medicine you can have what's called postural (or

orthostatic) hypotension.� That is, when you first stand up

or sit up, you're getting out of bed or you stand from a

chair, your blood pressure can fall because your blood

vessels aren't contracting.� That could be one side effect.

Another side effect, you can have problems with potency.

Almost all blood pressure medicine can interfere with sexual

function.� One of the special problems with ACE Inhibitors,

very uncommon, is a cough.� People can have this cough, that

can't seem to come under control.� It's very rare, but when

it happens, it can be a problem.� Fortunately, there are

other medicines to take.� So those are some of the general

thoughts about the ACE Inhibitors. �In general, they are

considered to be pretty darn good and pretty effective

medicine, especially for people who have diabetes with a

little bit of protein in the urine.

There are three or four ways to measure the protein

spillage, microalbumin, that is characteristic of kidney

disease.� One is a 24-hour urine.�� Another test you can do

is called the spot test, where you get a urine sample and

you look at the amount of protein compared to the amount of

another substance called creatinine.� And then there are a

couple of what's called dipstick tests.� We can put a strip

into the urine and see if albumin is present.� We can do

that now, so we can know if your kidneys are failing early.

For the eyes, we now know what to look for.� In this

day and age, only about 40%, 50% of people are having their

eyes examined well, and at regular frequencies.� We knew

twenty years ago that if you looked in the eyes and you

found changes and you got laser treatment, that could help

reduce the likelihood of going blind.� We knew that 20 years

ago, but we're still having trouble getting that done

regularly.

I wanted to cover neuropathy, the nerve damage produced

by diabetes, the damage done by high blood sugar on the

nerves, especially in the legs and feet, sometimes in the

hands.� There are different kinds of neuropathy.� But

peripheral neuropathy tends to have different kinds of signs

and symptoms.� It can manifest itself by having slightly

cold, numb feet.� On the other hand, it can be painful, if

different size nerves are affected.� Or it can make your

feet so incredibly sensitive that you don't even want the

bed sheet to touch you.� It can be all those things or just

some of them.� The problem with neuropathy is not

necessarily the problems of having it, but also that it

causes your foot to change shape, to be exposed to bruises

and bumps that it normally wouldn't be.� You can step on a

nail, or a stone, or have your sole of your shoe double up,

and you don't know it.� Pain can be a wonderful thing, in

that it tells you there's something wrong with your foot.

If you've lost the nerve function, you don't know it.� All

of us in the office have had experiences where people come

in, we say, "How're things going?"� "Great, Any problems

with this that and the other thing?", "No."� You take off

their socks, look at their socks, there is some pus and

blood, and there's a big hole on the bottom of the foot.

The people haven't even sensed it and so then the ulcer is

associated with amputation.

Again, we know that the neuropathy can very much be

prevented with good sugar control and that there are

medicines now being studied, such as the Aldose Reductase

inhibitors, that tend to stop the conversion of high sugars

into a compound called Sorbitol. �And the scientific

rationale behind why this particular medicine is available?

Neuropathy is very common.� It's probably the most common

difficulty with diabetes.� The major cause of amputation is

peripheral neuropathy.� Highly preventable, highly

treatable.

My own sense is that there are going to be more people

with diabetes.� We don't yet know enough how to stop that,

although I think we'll know enough within three to four

years.� But once someone gets diabetes, we know how to stop

them from having problems.

We don't need a lot more science to tell us how to do

it.� What we need are to find ways to get it done.� And

that's not an easy thing, because it involves making sure

doctors know and nurses know, and making sure that people

with diabetes feel they have the right, opportunity, and

responsibility to demand these things, and those aren't easy

things to deal with.� But I think, today, we can do a lot.

I think tomorrow we're going to know a lot more; and I would

see, at the end of that rainbow, for people with diabetes,

not a pot of baked beans, but a pot of gold.� Thanks.