LEADING THE WAY TO A CURE FOR DIABETES

Summer/Fall 2005

INSIDE:• Helping children manage diabetes

• Learning about metabolic syndrome

• Using gene therapy to combat CVD

• Uncovering factors affecting fetal growth

• Hot Topics/Research Updates

Message from the American Diabetes AssociationResearch Grant Review Panel Chair

With the number of Americans affected by diabetes rising each year, the American

Diabetes Association’s commitment to funding quality diabetes research has never been

more important. More than 18 million Americans have diabetes, but unfortunately

nearly one-third of those people do not know it. I, along with the ADA, feel that clinical research, research directly

involving patients, is critical to halting the spread of diabetes across our nation and to providing better care to those

who already have the disease.

The National Institutes of Health (NIH) also recognizes the importance of taking research results from the laboratory

and quickly and safely moving them to human trials. The NIH Roadmap to Success stresses the need for

“translational” research—research that focuses on taking discoveries learned in the laboratory to real-world use in

patients. It is during this crucial step when discoveries are taken from “bench to bedside” that real progress can be

made in fighting disease.

Over the past year, the ADA has made significant changes to its research program that demonstrates its dedication to

funding clinical research. The creation of the Distinguished Clinical Scientist Award emphasizes the Association’s

commitment to clinical research by providing funds to outstanding researchers and thought leaders who have

advanced the field of patient-oriented diabetes research. This award provides funding for established investigators who

have made novel or watershed contributions to clinical diabetes research and who will continue to provide leadership

in their research areas.

The Association’s Clinical Research Award has become more focused on funding smaller studies whose purpose is

to prepare for a larger investigation, as well as funding sub-studies which are part of larger, existing studies funded

by government organizations such as the NIH. I believe this is an important change that will lead to these grants

having better outcomes and more specific results in the three-year timeframe in which the research is carried out.

Health services research and behavioral research which help answer questions about healthcare delivery, health

education and how to improve services for patients with diabetes are now a major focus of the Clinical Research Award.

This issue of Forefront provides an opportunity to learn more about some of the brightest minds and most interesting

work being done in the field of diabetes research. Both clinical and laboratory-based research studies are featured, and

both kinds of research are important to finding a cure and providing better treatments for people with diabetes. Back

by popular demand, we have again included a “Hot Topics” section and “Research Updates” section, which highlight

some of the latest and most innovative research into diabetes care and illustrate some of the many successes of

ADA-funded research. I hope you find this issue of Forefront to be educational as well as inspiring.

Sincerely,

Timothy J. Lyons, MD

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Artistic rendering of the recruitmentof the adapter protein APS to the insulin receptor, a potentiallyimportant molecular event forinsulin-stimulated glucose uptakeinto cells. This figure is based onthe three-dimensional structurereported in Hu et al., Mol. Cell12, 1379-1389 (2003)

Photo submitted by Stevan Hubbard, PhD New York University School of Medicine

Co-editors:Tory AsfahaniElizabeth Guzman

Design:Nichols & Duncan, Inc.

Table of Contents

Message from the ADA Research Grant Review Panel Chair, Timothy J. Lyons, MD 1

RESEARCH I Type 1Andrew Muir, MDClinical Research AwardComputer-assisted training (CAT) in self-managementeducation of children with newly diagnosed type 1 diabetes and their families 3

RESEARCH I Type 2Robert R. Henry, MDMentor-Based Minority Postdoctoral FellowshipThe effects of pioglitazone on lipid and glucose metabolism and cardiovascular risk factors in subjects with the metabolic syndrome 7

RESEARCH I ComplicationsHelen Vlassara, MDResearch AwardTreatment of diabetic atherosclerosis by gene therapy 11

RESEARCH I TargetedPatrick M. Catalano, MDTerry & Louise Gregg Diabetes in Pregnancy Research AwardRole of placental leptin in the regulation of fetal growth and adiposity 15

Hot Topics 19

Research Updates 24

Message from the ADA Research Foundation Chair, Mr. Don Wagner 34

LEADING THE WAY TO A CURE FOR DIABETES

Andrew Muir, MD

Occupation: Associate Professor of Pediatrics and Chief, Pediatric EndocrinologyMedical College of GeorgiaAugusta, Georgia

Professional Focus: Early diagnosis and prevention of type 1diabetes; improving access for individuals with diabetes to high quality care; prevention of death from cerebral edema.

Outside Interests: Spending time with my four children and golf

Research Funding: Clinical Research AwardComputer-assisted training (CAT) in self-management education ofchildren with newly diagnosed type 1 diabetes and their families

Amount Awarded: $300,000

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Helping Children Manage Type 1 Diabetes

orking many summers at a youth camp in

my home town of Toronto, Canada provided

an excellent opportunity for me to be part of a

nurturing and caring community at a young age.

I loved the great outdoors and enjoyed watching

children develop an early appreciation for the

earth’s beauty.

It was also around this time that I became

interested in pursuing a career in medicine.

Naturally, I considered going into pediatrics.

In my first year of medical school, I took an

elective in genetic research. Although I was not

consciously aware of it at the time, my interest in

research was sparked by this elective. As I look back,

I recall frequently skipping my lectures so I could

work on experiments in the lab. (Don’t worry, I

read the lecture notes and passed all my exams.)

Pediatric endocrinology offered the opportunity to

help people with difficult and sometimes unusual

problems and is a specialty with a heavy research

emphasis. As a senior medical student and a

pediatrics resident, I was inspired by a tremendous

mentor, Dr. Denis Daneman, a pediatric

endocrinologist at the Hospital for Sick Children

in Toronto.

By the time I finished my pediatrics training, I was

certain I wanted to do research in diabetes because

I found myself intrigued by the complexity of the

autoimmune response that causes the condition.

Today, in addition to conducting research, I

continue to work with children in a nurturing and

caring community—only now my specialty in

pediatrics allows me to focus on a full range of

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RESEARCH I Type 1

health issues concerning children with type 1

diabetes while working alongside other dedicated

professionals who all want to empower children

with type 1 diabetes and their families to achieve

and maintain healthier lifestyles.

While I love being a physician who has been

involved with diabetes research for 16 years and

could not imagine doing anything else, I recently

noticed a disturbing trend throughout the diabetes

community.

Simply put, the number of children with diabetes

is growing at a rate much faster than the supply of

pediatric diabetes education specialists to care for

them. We therefore need new models to improve

the efficiency of our care without reducing the

effectiveness of our current interventions.

Because the American Diabetes Association has a

long history of focusing on patients and projects

that will translate quickly to clinical practice, I

turned to the Association to seek the funding that

would support our investigation of a new computer-

based education program designed to help families

with a child newly diagnosed with type 1 diabetes.

Our ADA funded grant, Computer-assisted training

(CAT) in self-management education of children

with newly diagnosed type 1 diabetes and their

families, is taking place at the Medical College of

Georgia and the University of Florida over a three-

year period. In this investigation, one half of the

eighty participating families will complete a

Web-based computer-assisted training (CAT)

course that will supplement three face-to-face

visits with the diabetes team. The other half will

complete diabetes education in eight traditional

face-to-face sessions with the diabetes team.

We will examine costs to the providers and to the

families to treat diabetes over the first year and use

validated surveys to measure the outcomes of the

two education programs. The outcomes will include

diabetes knowledge and problem solving skills,

psychological and social adjustment to life with

diabetes, and satisfaction with the care provided

by the diabetes team.

Because young children cannot usually

cope with the pace of traditional diabetes

education, development of a new CAT

program for children in grades 1-3 is

also proposed. If it proves effective, CAT could

rapidly be made widely available.

This project will also compare the cost and

effectiveness of traditional diabetes education

to the cost and effectiveness of a new computer-

assisted model of education. Families of children

with newly diagnosed type 1 diabetes will receive

factual information about diabetes using

animated modules that are posted on the Web.

Completion of these modules will reduce the

number of in-person visits with a diabetes

educator required to become competent in

diabetes care. Patients and their caregivers will be

able to complete their education using a schedule

that is suitable to their needs at a place more

convenient than the clinic or doctor’s office and,

obviously, miss less work or school to complete

their initial diabetes education.

This program will also determine whether

diabetes educators can offer patients better

service by shifting some of their current teaching

responsibilities to computers. This should

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“...the number of children

with diabetes is growing at

a rate much faster than the

supply of pediatric diabetes

education specialists...”

5

allow educators more time to effectively solve

the individual’s unique problems while analyzing

blood glucose results from both new and

established patients.

By the end of the trial, we expect to learn a

lot about who can benefit from independent

learning methods and when they are best applied.

Hopefully, we will also establish that the cost

of providing diabetes education can be reduced

by using new technology.

Computer-assisted education is unique among my

diabetes research efforts because it has immediate

applicability to patients. My colleagues and I hope

that we will provide a means for allowing patients

to receive the personal care they need and deserve

in a healthcare system that increasingly restricts

opportunities for personal interaction between

providers and patients.

If our hypothesis is supported by the trial results,

it will be much easier to convince physicians and

third party payers that computer-assisted training

of people with diabetes is a viable option to repeated

in-person visits.

As a professor, I am obliged to explore novel

methods of improving the lives of patients and

families with diabetes. As a physician, my aim is

to provide the highest level of service and clinical

quality while giving patients and their families the

best information and advice they need to make

informed decisions about managing their illnesses.

With this particular ADA-funded project, however,

the expected outcomes and benefits will extend

beyond a finite group of individuals to ultimately

help a large number of people with diabetes. And

here lies the beauty of our work—the far

reaching implications.

The American Diabetes Association is also far

reaching in its scope and plays a vital role in

the daily lives of people with diabetes. No other

organization is as active in communities in the

dissemination of information to individuals with

diabetes, health care providers, legislators, etc.

As professionals, we rely on the ADA to establish

and maintain professional standards through its

annual Clinical Practice Recommendations,

disseminate new research through its journals

and annual Scientific Sessions, and help our

patients learn about their disease through books,

local events, and so much more.

To the donor who has graciously given of his or her

resources to make the ADA the world class leader that

it is, I must say that ‘thank you’ is not enough.

Irrespective of your contribution amount, my

experience is that the motivation of ADA donors

is as true as one can find. For whatever reason that

you have been moved, you have made a pledge to

make life better for someone who has diabetes.

As an investigator, I take the investment and trust

that is placed in me very seriously and feel

privileged to have been funded by the ADA for a

project related at least initially to type 1 diabetes.

Type 1 diabetes research is headed steadily towards

a cure and I hope to be a part of the team that finds

the cure for type 1 diabetes. Improved diagnosis of

islet autoimmunity will open non-toxic avenues of

intervention that can be instituted before beta-cell

loss reaches a clinically important stage and

transplantation of cadaveric islets should give way

to implantation of genetically modified self-cells,

stem cells, and man-made devices.

I also foresee a new emphasis among pediatricians

on the prevention of obesity and more aggressive

treatment of risk factors for cardiovascular disease.

Over the next decade, I believe education about

healthy lifestyle and diabetes will become more

important for children than it ever has been before.

The professional paths of all diabetes investigators

are all headed to the same place—cure—but we

are taking different routes to get there. For today,

I am tremendously exhilarated to work hard in

contributing smaller pieces to the big puzzle while

providing every person with type 1 diabetes the

information, skills, equipment, and motivation

they need to tackle their disease.

As for tomorrow, and with your ongoing support,

there is no doubt that we will see many more

exciting, far reaching discoveries in diabetes

research. ■

“...the American Diabetes

Association has a long

history of focusing on

patients and projects that

will translate quickly to

clinical practice...”

6

McCabeGlossary

Scientists at the Medical College of Georgia have been

zeroing in on the genetic causes of type 1 diabetes.

Jin-Xiong She, PhD, joined the Medical College of

Georgia in 2002 as Professor and Eminent Scholar

in Genomic Medicine and Director of the college’s

Center for Biotechnology and Genomic Medicine.

Prior to coming to Georgia, Dr. She was the Director of

Research for the University of Florida Diabetes Center

and the Diabetes & Digestive & Kidney Diseases

Biotechnology Center. While there, his research team,

including Mark Atkinson, PhD, the American Diabetes

Association’s 2005 Outstanding Scientific Achievement

Award winner, Andrew Muir, MD and Desmond Schatz,

PhD, developed a prospective study of newborns

in the state of Florida. The study, Prospective

Assessment in Newborns for Diabetes Autoimmunity

(PANDA), is designed to identify newborns with genes

that put them at high risk for type 1 diabetes. PANDA

is funded by the National Institute of Diabetes &

Digestive & Kidney Diseases of the National Institutes

of Health. While researchers continue to study infants

in Florida, Dr. She has expanded the study to now

include newborns in the state of Georgia. The PANDA

study will not only help identify newborns at risk for

type 1 diabetes, but will also allow researchers to

understand more about when the disease process

starts. Insights into how the disease process begins

may also help scientists figure out how to prevent the

disease from developing.

Not long after his arrival at the Medical College of

Georgia, Dr. She and his former postdoctoral fellow,

Cong-Yi Wang, MD, published a major type 1 diabetes

finding in the journal, Nature Genetics (August 2004).

Drs. She and Wang announced that a gene known as

SUMO4 is one of the

key genes contributing

to type 1 diabetes.

But that isn’t all. They

also discovered how

the gene is involved in

the development of

diabetes. Thanks to

their efforts, researchers

now know that SUMO4

controls the activity of

the molecule NF�B, which in turn controls the actions

of proteins called cytokines which regulate immune

system responses. Dr. Wang found that when a

mutation in the SUMO4 gene occurs along with an

environmental trigger, such as a viral infection, cytokine

production increases and these cytokines direct the

body’s immune system to attack the insulin-producing

beta cells of the pancreas.

Dr. Wang continues his study of the genetic causes

of type 1 diabetes through his ADA Junior Faculty

Award, Role of TAB2 and SUMO4 in type 1 diabetes

pathogenesis. It is believed that multiple genes are

involved in the development of type 1 diabetes, and

the purpose of Dr. Wang’s ADA grant is to not only

further study SUMO4, but also determine the role of

a gene known as TAB2 in the progression of type 1

diabetes. Dr. Wang will also verify whether environmental

triggers play a role in the expression of this gene as

they do for SUMO4. Learning more about TAB2 and

SUMO4 will help researchers to identify children at risk

for type 1 diabetes. Dr. Wang also hopes that his

study will be able to determine whether these genes

can be targeted for therapeutic interventions to prevent

or cure the disease. ■

Preventing and Reversing Type 1 Diabetes at the Medical College of Georgia

6

Cong-Yi Wang, MD

X

uccess in life as well as in science requires

creating promising possibilities. As a young

child born and raised in Winnipeg, Manitoba,

Canada I did not have the clear cut aspiration to

become a doctor nor medical researcher.

Yet, I always knew that by following my interests

in the areas that were most stimulating to me, I

would end up doing what I love most in life.

Genuine intellectual curiosity, coupled with the

fact that I always wanted to help people, led me to

become a medical doctor. However, when I went

into medicine, I quickly knew that I needed more

than being a practitioner. Once involved in

medical research, the discovery of new findings, no

matter how small, was intriguing and made me

want to know more about living things and how

they developed. By gathering more information

and expertise, wonderful opportunities soon

unfolded that eventually led me to the rewarding

and challenging area of endocrinology research.

My interest in endocrinology and, in particular,

diabetes began in earnest while I was an intern

and a resident in internal medicine. Following a

serious auto accident that landed me in the

hospital for nearly a year, and while still on

crutches, I was offered the opportunity to be a

fellow in diabetes and endocrinology.

Even then, almost 30 years ago, it seemed

obvious that the prevalence of diabetes would

increase dramatically in succeeding decades.

I was also intrigued by the complexity of the

disease and the multiple system involvement for

the diabetic patient.

Robert R. Henry, MD

Occupation: Professor of Medicine, University of California, San DiegoChief, Section of Endocrinology and MetabolismDirector, Center for Metabolic Research San Diego VA Healthcare System, San Diego, California

Professional Focus: Adipocyte (fat)–skeletal muscle interactionsincluding adipocyte secretory products and skeletal muscle insulinaction/resistance; which factors regulate adipocyte secretoryproducts (adipokines) and how they influence insulin action inskeletal muscle.

Outside Interests: Spending time with family, sailing, hiking.

Research Funding: Mentor-Based Minority Postdoctoral FellowshipThe effects of pioglitazone on lipid and glucose metabolism andcardiovascular risk factors in subjects with the metabolic syndrome

Mentor-Based Postdoctoral FellowshipTranslational research of insulin resistance, obesity, and type 2 diabetes

Amount Awarded: $205,000

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Metabolic Syndrome: A Risk Factor for Type 2 Diabetes

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This was also a time when the basic causes of

diabetes were being elucidated and there was

immense opportunity for scientific growth and

understanding. Cell biology, immunology and

molecular biology were coming of age and the

opportunity to translate this to diabetes was

unlimited.

During my fellowship, it became clear to me

that I wanted to pursue a career in diabetes

research, because the spark that started when I

was an intern and resident soon became a flame!

I just found the disease and its complications to

be fascinating. Today, my burning desire is to

learn more about the metabolic syndrome.

Metabolic syndrome is the term used for several

specific physical problems that occur at the same

time and increase a person’s risk for type 2

diabetes, heart attack, stroke, and premature

death. Nearly 25% of American adults have

metabolic syndrome. The diagnosis is made if

a person has at least three of the following

characteristics:

• A waist larger than 40 inches (for men) or

35 inches (for women);

• Triglyceride (a type of fat) level of 150 milli-

grams per deciliter (mg/dL) of blood or higher;

• High-density lipoprotein (HDL, or “good”)

cholesterol blood level of less than 40 mg/dL

(for men) or 50 mg/dL (for women);

• Blood pressure of 130/85 mm Hg or higher, or

the need to use blood pressure medication; and,

• Fasting blood glucose level of 110 mg/dL or

higher.

Most people with metabolic syndrome also

have insulin resistance meaning that cells in

the body resist the action of insulin, the hormone

that enables glucose to enter cells from the

bloodstream. The pancreas increases insulin

production to compensate for the resistance, but

with time, this effort may fail. Blood glucose

levels rise, eventually leading to type 2 diabetes.

While we know that genetic (heredity) factors,

severe overweight (obesity), an inactive lifestyle,

poor diet, a smoking habit, and older age all

contribute to insulin resistance and to metabolic

syndrome, we don’t understand exactly what

causes insulin resistance.

This is why I sought American Diabetes

Association funding for one of my current research

projects, The effects of pioglitazone on lipid and

glucose metabolism and cardiovascular risk

factors in subjects with the metabolic syndrome.

This investigation explores how fat—too much in

all the wrong places—accelerates the

development of diabetes and, in particular, how fat

induces insulin resistance and an increased risk of

cardiovascular disease. Obesity and the

development of the metabolic syndrome is

epidemic in the U.S. It is, in fact, present in a

majority of people with type 2 diabetes as well as a

substantial number of type 1 patients. We need to

understand how fat worsens the diabetic state,

makes it more difficult to control glucose levels

and how it contributes to increased vascular

disease. If we don’t curb the adverse effects of fat,

an ever increasing number of Americans will

develop diabetes and its dangerous complications.

Besides disorders of glucose metabolism, the

metabolic syndrome also involves altered free fatty

acid (FFA) metabolism, which could itself

contribute to insulin resistance. Free fatty acids

are by-products of fat metabolism occurring in fat

tissue. Our project is designed to determine if

impaired FFA metabolism in the metabolic

syndrome can be reversed by treatment with the

anti-diabetic drug, pioglitazone (Actos), and if

such improvement would also impact the insulin

resistance acquired from acute elevations in

circulating FFA levels.

Determinations will be made of the effect of drug

treatment on both the balance between glucose

metabolism and FFA metabolism in the whole

body, and pathways of glucose and FFA

metabolism in adipose tissue and skeletal muscle.

Studies in isolated tissues or cells will allow

identification of the specific molecular sites of

defects in metabolism and insulin resistance

RESEARCH I Type 2

“The ADA gave me my first opportunity to developinto a scientific researcherand I continue to feel part

of their team.”

8

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and help determine if the effects of pioglitazone

on metabolism and insulin action are due solely

to reductions in FFA levels or if other mechanisms

are involved. The effects of treatment on

cardiovascular risk factors will also be followed

to see if a favorable profile (protective against

cardiovascular disease) can be established.

This study should provide basic information about

mechanisms of metabolic control and help identify

targets for treatment for both preventing the

negative consequences of the metabolic syndrome

and reducing the progression to type 2 diabetes.

Lifestyle changes are the first step in treating

metabolic syndrome. Topping the list for insulin

resistance is weight loss through increased

physical activity and a lower intake of calories.

Best results have been achieved among those who

lose seven percent to 15 percent of their baseline

weight. Increasing the intake of fiber (found in

vegetables, whole grains, and fruits) helps lessen

insulin resistance as does quitting smoking.

To date, probably the most rewarding experiences

as a medical doctor and researcher have been

sharing in my patients’ and their loved ones

euphoria and gratitude when they achieve a

happier human existence through better health.

To help in making ill patients feel better is really

quite satisfying.

On the other hand, the most difficult challenge we

sometimes face as care providers is dealing with the

devastating complications after diabetes takes its toll

—despite the best efforts of the patient and mine.

Medical researchers like me also experience

another difficult challenge. We find, at times,

that it is not easy to get people to understand the

value and promise of research to future care and

ultimate prevention.

Without research, we would not have new

discoveries and this can cause so many within the

diabetes community to become discouraged and

thus lose interest. By finding new ways to fight

diabetes, everyone is encouraged to work harder

because it is research that makes these

improvements in treatments possible.

And this is why the work of the American Diabetes

Association is so important.

Not only is the ADA dedicated to improving the

lives of people with diabetes and to discovering a

cure, it also focuses a large part of its efforts on

research and funding investigators in all areas

of diabetes. It has also funded many important

discoveries in recent times.

Moreover, at the core of the ADA are the volunteer

and donor who assure that the organization is lean

and highly effective. I have been thoroughly

impressed with the overall organizational structure

and the dedication of all the staff. The ADA’s

mission is clear and effective, but requires the

consistent involvement of its volunteer constituents.

It is indeed an honor and privilege to receive

ADA funding and is indicative that my personal

research interests are worthy of funding and

further exploration. The ADA gave me my first

opportunity to develop into a scientific researcher

and I continue to feel part of their team. Over the

past 20 years, I have received many types of

research awards from the ADA and, currently, I

have two mentor-based fellowship awards (see

“Young Scientist in Training – Brian Escala

Chavez, MD” on page 10).

These awards allow me to attract young

investigators with substantial promise who, with

my guidance and direction, will hopefully lead the

next generation of diabetes discovery. Obviously,

the ADA has not only been a strong and consistent

supporter of my personal research efforts but it

also contributes in major ways to the training of

new clinician-scientists.

To the readers of Forefront whose generosity funds

the ADA Nationwide Research Program, I would

say that you have contributed to a noble and

worthwhile cause—one that uses your

contributions wisely for the betterment of those

with diabetes and those at greatest risk. I assure

you that it is money well spent, earmarked for the

most worthy of research projects with the highest

likelihood of generating impactful discoveries.

Because of rapid advances in science, today more

than ever we have an opportunity to take new

advances and translate them into tangible benefits

for people with diabetes. Such progress could not

have happened without you and can only continue

with your ongoing generosity. Like you, I am also

a proud Pinnacle Society member and plan to

keep on supporting the ADA in every way possible

and, with great enthusiasm, work toward and look

forward to a world without diabetes. ■

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Brian Chavez received his Bachelor’s degree in

bioengineering from the University of California, San

Diego, and his MD from the Medical College of

Wisconsin in Milwaukee. After earning his medical

degree, Dr. Chavez returned to San Diego for his

internship and residency, and is now completing his

postdoctoral work under the guidance of Dr. Robert

Henry through an American Diabetes Association

Mentor-Based Minority Postdoctoral Fellowship Award.

During his college years, Dr. Chavez worked in the area

of biomedical engineering, developing glucose sensors

for people with diabetes. While this was an interesting

area of research, Dr. Chavez admits, “I realized I wanted

to work with people rather than be ‘behind the scenes’

and thus went to medical school and trained in internal

medicine, then pursued a fellowship in endocrinology.”

His research collaboration with Dr. Henry to study the

drug pioglitazone (Actos) and its effects on fatty acids

and glucose is helping Dr. Chavez achieve his dream of

working with patients and helping them to have a better

quality of life. Dr. Chavez explains, “We are now

recognizing what an epidemic obesity, the metabolic

syndrome, and diabetes are becoming in modern

society.” By studying pioglitazone, an “insulin sensitizing”

drug, and its mechanisms of action in people with the

metabolic syndrome, this research will provide insight

into the prediabetic state and help scientists to develop

new ways of preventing diabetes before it occurs.

His desire to help people can also be seen in his past

record of volunteer work at clinics caring for low-income

patients. Dr. Chavez even states that the most satisfying

part of his diabetes research experience has been

volunteering to educate patients about diabetes. “I recall

volunteering at a local non-profit conference where we

were able to spend some time with people during an

informal question and answer forum,” Dr. Chavez states.

“I remember how appreciative many people were after

what seemed to be ‘simple’ advice, such as explaining

what each medication they were taking was for and why

insulin doses needed to be adjusted.”

Asked about his reasons for wanting to help people with

diabetes, Dr. Chavez responded that he has many family

members and friends affected by diabetes, including his

grandmother who passed away from cardiovascular

complications of diabetes. “In the future,” Dr. Chavez

states, “I plan to continue caring for patients with the

metabolic syndrome and type 2 diabetes in clinical

practice, and hope to continue my involvement in

clinical trials and research.”

Encouraging Young Minorities in Research

The American Diabetes Association Mentor-Based

Minority Postdoctoral Fellowship Award was first offered

in 2002. The Association recognized a noticeable gap

in the number of minorities in the research arena, including

diabetes research, and the minority postdoctoral fellowship

award was developed to address this important issue. By

creating a training opportunity specifically for young

minority scientists, the Association felt it could help

encourage minorities who are under-represented in

clinical and basic science research to pursue a research

career in diabetes. The Association mirrors the National

Institutes of Health guidelines in its definition of

under-represented minority to include African American,

Hispanic/Latino and American Indian/Alaskan Native

individuals. The Association has funded 16 minority

postdoctoral fellowship awards since the program’s

inception, and is looking forward to seeing the program

grow as more mentors and young minority scientists

take advantage of this opportunity. ■

Young Scientist in Training—Brian Escala Chavez, MD

Brian Escala Chavez, MD

The ADA Research Foundation thanks TakedaPharmaceuticals North America, Inc. (TPNA) forsupporting the Mentor-Based Minority PostdoctoralFellowship Program. Dr. Brian Escala Chavez is a2004 recipient of the ADA-TPNA Mentor-basedMinority Postdoctoral Fellowship Award.

orn and raised in beautiful Athens,

Greece provided stimulating

surroundings and, of course, a most

historical and inspiring landscape for my

early intellectual curiosity. I was also

exposed to my father’s illness at a young

age at which time a strong desire was born

in me to alleviate the sense of helplessness

that accompanies this experience. This,

plus a deep curiosity about how the body

works and how disease evolves, made me

want to become a physician as well as a

medical researcher.

When I arrived at the Rockefeller University

in New York more than 25 years ago to

begin my post-doctoral training in medical

research, I found myself surrounded by a

group of brilliant scientists that was just

about to discover a new type of hemoglobin

modified by glucose. This molecule was

named glycosylated hemoglobin A1c and

was soon established as a highly reliable

indicator of the average blood glucose

levels of diabetic patients over a period of

several weeks.

The enormous importance of the discovery

of A1c soon became apparent and its

revolutionary impact on the traditional

treatment of diabetes was about to unfold

nationally and worldwide. This was a most

exciting time in the field of diabetes and I

found myself captivated by the dramatic

benefit that a discovery like this provided in

the long-term well being of all individuals

with diabetes.

Helen Vlassara, MD B

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Using Gene Therapy to Combat Cardiovascular Disease in Diabetes

Occupation: Professor of Geriatrics, Medicine, Molecular MedicineDirector of the Division of Experimental Diabetes and AgingMount Sinai School of MedicineNew York, New York

Professional Focus: Understanding diabetes complications andinvestigating ways to curtail them.

Outside Interests: Spending time with family and friends, literature,competitive dancing, piano, drawing.

Research Funding: Research AwardTreatment of diabetic atherosclerosis by gene therapy

Amount Awarded: $300,000

11

Today, the clinical testing of A1c is of

paramount importance in assessing the

severity of diabetes and adjusting the treatment

of each patient with far greater accuracy.

While there has been tremendous progress

toward improving the management of diabetes,

particularly over the last 10 years, prolonged

hyperglycemia still occurs. However mild, it

still leads to severe vascular, renal and

neurological complications. Moreover, the

incidence of type 2 diabetes continues to rise

among adults (due to excessive eating and

lack of exercise) or older people (due to

extended longevity), but also among much

younger persons. This is extremely alarming

and a much greater effort must be mounted

toward understanding and reversing the

dismal demographics of the disease itself.

At the same time, until a definitive cure for

diabetes becomes available, the treatment of

its complications, especially vascular and

kidney disease, is a top priority for the

future of diabetes-related research because

individuals with diabetes are more likely to

develop far more serious cardiovascular and

renal disease than are non-diabetics.

Most adult individuals develop health

problems over the years, such as high blood

pressure and cholesterol, which increase

their risk for cardiovascular disease or

stroke. When combined with diabetes,

these risk factors add up to far greater

trouble. In fact, more than 65 percent of

people with diabetes die from heart disease

or stroke. With diabetes, heart attacks

occur earlier in life and up to four times

more frequently. By managing diabetes well,

this risk can be reduced but not eliminated.

Diabetic vascular disease continues to be

a major cause of death today. (For more

information on the link between diabetes and

cardiovascular disease, visit ADA’s Web site at

www.diabetes.org/diabetes-heart-disease-stroke.)

The majority of my work has focused on the

prevention and reversal of the cardiovascular

and renal complications brought about by

chronic diabetes, whether type 1 or type 2. It

is a well known fact that high levels of certain

sugars, like glucose in diabetes, provoke a

complicated series of chemical reactions (an

early product of which is A1c) which result in

a large number of sugar-protein or sugar-lipid

(sugar-fat) complexes called advanced

glycation end products or AGEs. These are

shown to accumulate in cells, tissues and

organs and cause gradual malfunction

and failure through chronic oxidant stress

and inflammation. Although several

experimental drugs have been identified that

can prevent this process, none have come

along far enough yet to make it to clinic.

In my nearly 30-year career in diabetes as a

scientist, I have always depended on the ADA

for its tremendous efforts in promoting

knowledge and research. Recently, I appealed

to the Association once again for the funding

of a novel research project designed to help

individuals with diabetes who are facing

perhaps one of the disease’s worst

complications—diabetic vascular disease.

This ADA-funded project, Treatment of

diabetic atherosclerosis by gene therapy,

focuses on an extremely powerful and

promising approach—gene transfer—that

may bring forth a novel therapeutic

intervention for the prevention of the vascular

disease that affects the well-being of most

individuals with diabetes.

We have identified a natural protein called

lysozyme which is present in the body,

normally helping to fight infections. This

protein can also capture toxic AGE, helping in

their disposal from the body through the

kidneys. We now plan to investigate the

potential of lysozyme as a new therapy

against diabetic complications. Using animal

“...individuals withdiabetes are more likely

to develop far moreserious cardiovascularand renal disease thanare non-diabetics.”

RESEARCH I Complications

12

models of type 1 and type 2 diabetes, and

crossing them with genetically manipulated

mice that carry large amounts of the

lysozyme gene, we have observed that high

levels of this protein appear to offer protection

from vascular and renal damage, despite the

presence of diabetes. This protein appears to

be unique in that it not only helps with the

removal of AGE from the body, but it also

counteracts the tendency of AGE to cause

excessive oxidation, inflammation and

eventual damage of tissues and organs. For

example, diabetic animals which typically

have high glucose and lipid levels, and

consequently develop severe vascular disease

(atherosclerosis), are significantly protected

from this serious problem if they carry high

levels of the lysozyme gene.

Based on these exciting findings, we plan to

introduce the lysozyme gene into diabetic

animals with the help of viral vectors. Viral

vectors are harmless viruses that can transport

desired genes into an animal’s cells. We will

use vectors similar to those that have been

already used in the treatment of many other

diseases in humans to evaluate the possibility

of this approach as a therapy for the long-

term complications of diabetes.

As a physician, I am constantly aware of the

odds faced by our patients with diabetes and

this is a reminder that only research can

favorably change these odds in a meaningful

way. Every day, the need for diabetes research

becomes increasingly more important

because the general public’s awareness

and education regarding diabetes and its

dangerous complications are not keeping up

with the prevalence of the disease.

Indeed, the most critical and time-resistant

difficulties I have encountered throughout

my career have always been the low levels

of public awareness or education related to

diabetes and the persistently low priority

given to this disease by the general

medical/scientific and federal agencies. Even

today, despite the huge efforts made to alert

the general population about the “epidemic

proportions” of diabetes, there is an overall

frustrating denial toward this disease and the

urgent need for effective strategies in terms of

educational tools developed for families and

schools, for the timely availability of new

treatments made to physicians and other

health professionals, and in particular, for

greater financial support of research.

There has to be a brighter outlook and this

is where the American Diabetes Association

comes in.

Throughout my career, I have been involved

with the ADA not only as a member and

repeatedly funded researcher, but also as

Chair of the Research Grant Review Panel,

Chair of the Council on Complications,

organizer of symposia, and as a member of

the Editorial Board of the journal, Diabetes.

I deeply believe in the importance of the

service that the ADA provides to all health

professionals, individuals with diabetes and

their families. The ADA is an indispensable

organization that has embraced all aspects

and needs of the diabetes community—

education, medical care and, of course,

research. It has supported my research ever

since I was a junior researcher and this has

continued to the present, long after I became

an established senior investigator. Fortunately

for so many of us in the research community,

the ADA has always appreciated the

importance of novel ideas and breakthroughs

and, in doing so, fulfills the role of a unique

organization set to utilize every potential that

years of experience in this field can offer.

I can only express admiration and respect for

the commitment and dedication that the

American Diabetes Association displays in

multiple ways that have enabled it to achieve so

much over the years and I am confident that

it will continue to be supported by the extremely

generous donors until the day the battle

against diabetes and its complications is won.

Thank you for your interest in diabetes research

and your gracious support of my life-long

commitment to eliminate this disease or, in

the meantime, to make the lives of those with

diabetes free of risk, healthier, longer and

more livable. ■

13

Dr. Helen Vlassara is in good company at Mount Sinai

School of Medicine. She joins Rosalyn Yalow, PhD, who

not only conquered social and professional barriers to

become a leading female medical physicist, but became

only the second woman in history to receive the Nobel

Prize in Physiology or Medicine in 1977.

Rosalyn Yalow was born Rosalyn Sussman in the Bronx,

New York in 1921. Demonstrating an early aptitude for

math, she graduated from Hunter College in New York

with a degree in physics, but because of a lack of interest

in women scientists, was forced to take a job as a

typist to a biochemist. However, in 1941, Dr. Yalow

unexpectedly received an assistantship from the

University of Illinois and became the first woman at the

school’s College of Engineering since 1917. While her

acceptance at the school was in part due to a shortage

of men eligible to attend (most were being drafted into

the military), she proved herself a talented researcher.

Dr. Yalow received her PhD in nuclear physics in 1945,

and then returned to New York where she became a

consultant and later a faculty member at the Bronx

Veterans Administration (VA) Hospital. Here she joined

Dr. Solomon Berson in conducting research on medical

applications of radioactive materials. It was this work

which would eventually lead Drs. Yalow and Berson to

develop a new technology known as radioimmunoassay

(RIA) to prove that the immune system could recognize

and respond to small molecules, such as insulin, in the

bloodstream. By binding animal insulin to radioactive

iodine, Dr. Yalow was able to determine the rate of

disappearance of insulin from the circulation of insulin-

treated patients, and determined that the patients

developed antibodies to the animal insulins. She and Dr.

Berson had, in effect, developed a tool for measuring

insulin levels in the bloodstream. In 1961, Dr. Yalow

received the Outstanding Scientific Achievement Award

of the American Diabetes

Association (sponsored by

Eli Lilly and Company) for her discovery and its

implications in the care of those with diabetes.

The American Diabetes Association presents the

Outstanding Scientific Achievement Award each

year to an individual researcher under age 45 who

has made an outstanding contribution to diabetes

research that demonstrates both originality and

independence of thought.

Despite the death of her colleague, Dr. Berson, in 1971,

Dr. Rosalyn Yalow persevered in her work and went on

to receive the Nobel Prize in Physiology or Medicine in

1977 for continued development of RIA in peptide

hormones. RIA now has multiple medical applications,

including screening blood for hepatitis virus, determining

effective levels of drugs and antibiotics in the blood,

detecting foreign substances in the blood, and even

testing hormone levels in infertile couples. Dr. Yalow

is now retired. The Bronx VA Hospital where she

performed her research is now affiliated with Mount Sinai

School of Medicine where Dr. Yalow holds the title of

Distinguished Service Professor.

Dr. Yalow’s accomplishments include not only her

professional work and awards received, but also her

determination to overcome the social and cultural

barriers faced by the women of her time. While she

found inspiration in the autobiography of Madame Marie

Curie, another Nobel Prize winner, young women are

already finding inspiration and have begun honing their

scientific talents thanks to Dr. Rosalyn Yalow. And it

is thanks to the contributions of talented women

researchers like Dr. Yalow and Dr. Vlassara at Mount

Sinai School of Medicine that we will continue to make

progress in the fight against diabetes. ■

Women in Research at Mount Sinai School of Medicine

14

Rosalyn Yalow, PhD

Patrick M. Catalano, MD We have all heard the worn out cliché

reminding us that “two heads are better

than one.” But maybe it is not as worn out as

it sounds. Yes, there are countless researchers

who do their best work alone and their ideas

and accomplishments are appreciated. Most

of us, however, are usually grateful for all the

help we can get.

In science, no researcher or idea stands alone.

We continuously build on one another’s work,

past and present. It is also especially important

to form a supportive network and have contact

with people who share similar research

interests because there are times when research

can be somewhat isolating. Partnering or

interdisciplinary research not only helps to

increase motivation and interest, but will also

contribute to highly successful research that

better qualifies for obtaining research grants.

Such is the case with my current partnership

with Dr. Sylvie Hauguel-de Mouzon, a

collaborating investigator on my ADA-funded

project, Role of placental leptin in the

regulation of fetal growth and adiposity.

The Terry and Louise Gregg ADA funding was

specifically granted for research in the area of

diabetes and pregnancy, including placental

leptin metabolism, which is a strength of

Dr. Hauguel-de Mouzon, and fetal overgrowth

causing overly large babies, which is a joint

interest of ours.

Based on our common interests related to

diabetes in pregnancy, as well as gestational

diabetes, we plan to develop research methods

that will lead to the prevention of fetal obesity

Diabetes in Pregnancy: Uncovering the Factors that Affect Fetal Growth

Occupation: Professor of Reproductive BiologyChairman of the Department of Obstetrics and GynecologyCase Western Reserve University at MetroHealth Medical CenterCleveland, Ohio

Professional Focus: Mechanisms related to the development ofinsulin resistance in pregnancy; fetal growth and body composition

Outside Interests: Jogging, squash, travel, and reading, especiallyhistory novels

Research Funding: Terry & Louise Gregg Diabetes in PregnancyResearch Award Role of placental leptin in the regulation of fetal growth and adiposity

Amount Awarded: $300,000

© S

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ne P

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15

which we believe may have potential long

term implications for both the children and

mothers.

The problem of obesity is epidemic, not only

in this country, but in the developing world.

While diabetes in pregnancy may represent

an interesting pattern in itself, our research is

leading us to believe that maternal obesity,

through metabolic mechanisms, may affect

fetal overgrowth which may in turn have

long term implications for the development

of diabetes and the metabolic syndrome (see

page 8) in children born to these mothers.

Because of the increased insulin resistance,

pregnancy demands more insulin in the body.

An inability of the body to keep up with this

insulin demand can lead to diabetes during

pregnancy. In addition, increased production

of molecules by the the placenta increases

insulin resistance, a diagnostic feature of

common diabetes. Diabetes during pregnancy

is a serious condition that endangers the

health of the unborn fetus and the mother.

While in the uterus, the development of the

fetus is totally dependent on the placenta.

The placenta is a unique and necessary

boundary between the mother and her fetus.

When a woman is or becomes diabetic during

pregnancy, the placenta receives all kinds

of signals and stimuli that may modify

placental function and, consequently, the

growth of the fetus.

One major complication of diabetic

pregnancy is excessive growth of the fetus.

Our research has shown that increased

amounts of fat tissue contribute to this

excessive growth, which creates a greater risk

of developing obesity and diabetes later in life.

Our team has previously shown that the

placenta controls fetal growth by producing

hormones that modify fetal nutrition. The

hormone leptin is produced in the adipose

tissue of the mother, the fetus and also in the

placenta. When a fetus is obese, particularly

in diabetic women, the placenta produces

more leptin.

In our ADA-funded project, we are

investigating the molecular basis of the

changes that occur in the placenta of diabetic

and obese women. Recently, we identified

placental signals which are associated with

an increase in fetal adipose tissue. The aim

of this project is also to learn how leptin

affects the growth of the fetus. We are

currently studying factors that stimulate the

production of leptin by the placenta. Our

studies compare lipids in the placentas of

diabetic mothers with lean and obese babies

in order to determine if their placentas

transport more lipids to their babies than

placentas of women without diabetes.

This investigation will permit us to better

define the role of leptin in pregnancy and

help us determine the factors that are

responsible for overgrowth and obesity of the

fetus. Once we understand the processes

related to fetal overgrowth, we can then

implement intervention measures to decrease

the risk of fetal overgrowth and then hopefully

long term complications such as obesity and

type 2 diabetes. Coupled with our clinical

studies, this investigation will help us improve

the means by which basic research can be

translated into clinical care of our patients.

Dr. Hauguel-de Mouzon and I consider this to

be an important investigation, especially

given the fact that more than 10 years after

the discovery of leptin’s role in pregnancy, it

continues to be poorly understood. This is

why we are so grateful for the ADA’s support

and consider receiving our award very

important for two specific reasons. First, ADA

funding helps us face the high cost of

RESEARCH I Targeted

“...offspring of diabeticmothers have a higher

risk of developingdiabetes and obesity

later in life.”

16

Sylvie Hauguel-de Mouzon, PhD and Patrick M. Catalano, MD

research studies in molecular biology.

Second, the funding is specifically used to

improve our understanding of the placental

function in a diabetic environment and its

consequences for the developing fetus; thus,

promoting diabetes research at the earliest

stages of life. Support for our project also

demonstrates the Association’s interest in

addressing pregnancy disorders that may have

long term consequences for infants, and the

value in basically “nipping the problem in

the bud” for preventing what may turn out to

be greater problems later in life.

To date, Dr. Hauguel-de Mouzon and I find

that one of the most difficult challenges we

face as researchers is to convince the scientific

community that diabetes is a lifelong disease

which often starts before birth. For many

years, diabetes in pregnancy has gained little

attention in regard to the importance of basic

research studies and funding. It is crucial to

recognize that there is more to it than the

clinical goals of providing the appropriate

dose of insulin to diabetic pregnant women.

It has also become quite obvious that

offspring of diabetic mothers have a higher

risk of developing diabetes and obesity later in

life. Researchers now believe that this may be

the result of the adverse environment in

which the fetus develops. This is known as

metabolic programming or fetal origin of

adult diseases. Thus, the worldwide epidemic

of obesity starting in adolescence and even

earlier in childhood may have some

components of prenatal origin.

We are really quite proud to have been

awarded this grant by the ADA both as

individual investigators and as a team

merging basic and clinical studies. We

sincerely hope that our unique approach

combining studies on mothers, placentas and

newborns will contribute to improving the

heath care outcome in diabetic pregnancy.

If we can determine that obesity at birth is

related to exposure to specific maternal

stimuli during pregnancy, then rational

plans for primary prevention rather than

treatment can be developed.

And because the funding for our research

project was largely due to the extraordinary

generosity of Mr. and Mrs. Terry and Louise

Gregg of Malibu, California, we would also

like to thank them for their remarkable

support and recognize that this work would

not be taking place had it not been for their

heartfelt desire to help struggling mothers-to-

be realize their dream of having healthy

pregnancies and healthy babies.

Both Dr. Hauguel-de Mouzon and I have been

affiliated with the ADA for many years. We

have both participated in multiple ADA

meetings and conferences and continue to

be thoroughly impressed with the level of

dedication our peers and colleagues

demonstrate toward their research efforts. I

personally have been involved with the local

ADA office in Cleveland as well as on a

national level and believe that the American

Diabetes Association has an excellent

combination of input from people in

families living with diabetes as well as the

commitment from the researchers aiming

to make life with diabetes more livable.

They are all to be commended.

We recognize that although investigators

occasionally make large strides, more

commonly it is through small steps built on

the work of others that we move forward in

our research. Much like a baby’s first steps,

we all start out walking before we learn to

run. In the long run, and thanks to the

unfailing generosity of the American Diabetes

Association donors, I see us crossing the finish

line together, hand in hand, in our race

toward the cure for diabetes. ■

17

The ADA supports gestational diabetes (GDM) research

in many ways. Through its core funding program and

support of government-run clinical trials, and by

organizing and funding scientific meetings focusing on

diabetes during pregnancy, the Association shows its

commitment to caring for women and infants affected

by this disease.

The ADA provides co-support to federally-funded

research programs which it feels hold significant promise

to affect the lives of individuals with diabetes or those at

risk for developing the disease. The Hyperglycemia and

Adverse Pregnancy Outcome Study (HAPO) is one such

program. Funded primarily by the National Institute of

Child Health and Human Development (NICHD) and the

National Institute of Diabetes, Digestive & Kidney

Diseases (NIDDK), the HAPO study is led by Boyd

Metzger, MD at Northwestern University in Chicago,

Illinois. The purpose of this study is to determine

whether pregnant women with hyperglycemia have a

higher risk of poor maternal, fetal and neonatal outcomes.

Investigators from 16 clinical centers around the world

are working together to examine glucose tolerance in a

multicultural, multinational and ethnically diverse group

of women in the third trimester of pregnancy. Their goal

is to obtain information on the relationship between

blood glucose levels in pregnant women and the risk of

certain adverse outcomes. This information will be used

to develop international criteria for the diagnosis of GDM.

Support from the American Diabetes Association has

enabled researchers to add two critical resources to the

main HAPO study that will greatly add to the study’s

overall results. First, c-peptide levels will be obtained

during the oral glucose tolerance tests performed on all

of the pregnant women participating in the study.

C-peptide is

a subunit of

insulin created

by the

pancreas, and is measured to determine the amount of

insulin being produced by the pancreas. Second, DNA

samples from both the mother and the infant will be

stored and will become a resource for later studies in:

predisposition to type 2 diabetes, obesity, hypertension

and cardiovascular disease in women who have had

gestational diabetes; fetal growth and long-term growth

and development, as well as risks of obesity and

diabetes, in their children.

The ADA is also proud to sponsor the 5th International

Workshop Conference on Gestational Diabetes

scheduled for November 11-13, 2005 in Chicago,

Illinois. The three-day program will bring together

researchers from around the world to discuss the

disease processes involved in the development of GDM,

management of GDM, and post-partum follow-up of

both women and infants. The goal of the meeting is to

encourage dialogue between researchers in an effort to

develop specific recommendations for further GDM

research. The NIDDK is also organizing a meeting

to be held in September 2005 on the long-term

consequences of the intrauterine environment on the

development of obesity and metabolic disease, with a

concentration on the effects of maternal obesity and

diabetes on children. These meetings are an example

of the commitment of the scientific community to study

the effects of diabetes in pregnancy.

By funding research and promoting collaboration among

scientists, the ADA hopes to find improved ways of

treating, preventing and ultimately eliminating diabetes

during pregnancy. ■

American Diabetes Association Support of Gestational Diabetes Research

18

T H E E X P A N D I N G P R O B L E M O F O B E S I T YHot Topics

Being overweight or obese and leading a sedentary

lifestyle are some of the leading risk factors for

developing type 2 diabetes, and nine out of 10 people

newly diagnosed with type 2 diabetes are overweight.

The body mass index (BMI) chart on the next page can

be used to determine whether a person is overweight

or obese. Individuals who are overweight have a BMI of

25.0-29.9, while those with a BMI greater than or equal

to 30 are considered obese. While the BMI chart is

used by many researchers and clinicians, there are

some who feel it does not accurately predict the

likelihood of developing a disease since abdominal

obesity (fat deposited in the abdomen around the

organs) has been shown to be a better indicator of

disease risk. Therefore, waist circumference has

become another useful indicator of obesity. Men

with a waist circumference greater than 40 inches

and women with a waist circumference greater than

35 inches are considered obese and, as one recent

study showed, are at greater risk for cardiovascular

disease. Unlike other diabetes risk factors like genetics

or age, a person’s weight and activity level are two

factors that may be possible to control. Because of

that, we are seeing an increased research focus on

obesity, diet and exercise.

The recently completed Diabetes Prevention Program

(DPP) was a major clinical trial funded by the National

Institutes of Health, National Institute of Diabetes &

Digestive & Kidney Diseases with support from the

American Diabetes Association. The purpose of the

study was to discover whether diet and exercise or the

oral diabetes medication, metformin (Glucophage),

could prevent or delay the onset of type 2 diabetes in

people with impaired glucose tolerance (IGT). IGT, also

called impaired fasting glucose (IFG) or “pre-diabetes,”

is a condition in which blood glucose levels are higher

Why lose weight?Americans have been flooded with newspaper and

magazine articles as well as television news stories

about obesity and diabetes. By now many people are

aware that there is an increasing incidence of obesity

in the U.S. The latest data from the National Center

for Health Statistics show that 30 percent of U.S.

adults 20 years of age and older—over 60 million

people—are obese. The prevalence of overweight

among children and adolescents has also risen

alarmingly over the past three decades. National

Health and Nutrition Examination Survey (NHANES)

data over the past 30 years has indicated the

prevalence of overweight in 6-11 year-olds has almost

quadrupled and the prevalence in 12-19 year-olds

has increased 2.5 fold. The most recent 1999-2000

NHANES data estimates that 15 percent (almost nine

million) children and adolescents ages 6-19 are

overweight. The 1999-2000 findings for children and

adolescents suggest the likelihood of another

generation of overweight adults who may be at

increased risk for obesity, as well as related

cardiovascular disease and type 2 diabetes.

19

than normal (110-

125 mg/dL) but

not high enough

for a diagnosis of

diabetes (126

mg/dL or higher).

Results of the DPP

study showed that

losing even a small

amount of weight

(five to seven

percent of body

weight) through

diet and exercise

can reduce the risk

of developing

diabetes by approximately 58 percent across all age

and ethnic groups, and the results for older study

participants were even more striking with the risk of

diabetes reduced by 71 percent. Study participants

who received metformin had a 31 percent reduced risk

of developing diabetes, however metformin was shown

to be most effective in younger individuals age 25–44

years who were at least 60 pounds overweight.

Obesity can also contribute to a disorder called

the “metabolic syndrome.” Also known as “insulin

resistance syndrome” or “syndrome X,” the metabolic

syndrome is a combination of metabolic problems

including obesity, high blood pressure and high

cholesterol levels, which can lead to hardening of the

arteries, cardiovascular disease and kidney disease.

There is some controversy surrounding the precise

definition of metabolic syndrome. While the American

Diabetes Association does not endorse one specific

definition, there are some organizations and clinicians

that do use the criteria developed by the National

20

Heart, Lung and

Blood Institute’s Third

Report of the National

Cholesterol Education

Program Expert

Panel on Detection,

Evaluation, and

Treatment of High

Blood Cholesterol

in Adults (Adult

Treatment Panel III).

Known as the ATP III

criteria, this group

defined metabolic

syndrome as having

any three of the

following five symptoms: abdominal obesity determined

by waist circumference, high triglycerides > 150 mg/dL,

low HDL or “good” cholesterol (<40 mg/dL for men and

<50 mg/dL for women), blood pressure > 130/85

mmHg, and fasting blood glucose levels > 110 mg/dL.

While not everyone has adopted this definition, most

agree that the more symptoms a person has, the more

at risk they are for developing cardiovascular disease or

other complications. Metabolic syndrome affects one

out of every five overweight people.

Many people are able to lose weight by making

changes to their diet and increasing their amount of

exercise. Exercise not only promotes weight loss by

burning excess fat and increasing muscle mass, but it

also improves the body’s response to insulin which can

make a big difference to people who are insulin

resistant. Reducing the number of calories eaten per

day and controlling portion sizes can also contribute

to weight loss, which may help some people with

diabetes reduce or eliminate their need for oral

Weight in Pounds120 130 140 150 160 170 180 190 200 210 220 230 240 250

4'6" 29 31 34 36 39 41 43 46 48 51 53 56 58 60

4'8" 27 29 31 34 36 38 40 43 45 47 49 52 54 56

4'10" 25 27 29 31 34 36 38 40 42 44 46 48 50 52

5'0" 23 25 27 29 31 33 35 37 39 41 43 45 47 49

5'2" 22 24 26 27 29 31 33 35 37 38 40 42 44 46

5'4" 21 22 24 26 28 29 31 33 34 36 38 40 41 43

5'6" 19 21 23 24 26 27 29 31 32 34 36 37 39 40

5'8" 18 20 21 23 24 26 27 29 30 32 34 35 37 38

5'10" 17 19 20 22 23 24 26 27 29 30 32 33 35 36

6'0" 16 18 19 20 22 23 24 26 27 28 30 31 33 34

6'2" 15 17 18 19 21 22 23 24 26 27 28 30 31 32

6'4" 15 16 17 18 20 21 22 23 24 26 27 28 29 30

6'6" 14 15 16 17 19 20 21 22 23 24 25 27 28 29

6'8" 13 14 15 17 18 19 20 21 22 23 24 25 26 28

Heig

ht in

Fee

t and

Inch

es

Underweight Healthy Weight Overweight Obese

Note: This chart is for adults (> 20 years old)

21

Hot Topics

Oral Medications to Treat ObesityThere are several prescription drugs now available to treat obesity. Weight loss drugs are usually not recommended

for those who are only mildly overweight unless there are other serious health problems such as diabetes or heart

disease. A recent article in the April 5, 2005 issue of Annals of Internal Medicine reports on the results of a study to

assess the safety and effectiveness of U.S. Food and Drug Administration (FDA) approved weight loss medications

and other medications used for weight loss. Researchers reviewed 79 clinical trials involving dietary intervention

plus the following obesity drugs:

Generic name Brand name Method of action

sibutramine Meridia appetite suppressant

orlistat Xenical prevents absorption of fats

phentermine Adipex-P, Fastin, Ionamin, Oby-Trim appetite suppressant

diethylpropion Tenuate appetite suppressant

fluoxetine Prozac primarily for depression; balancesnatural brain chemicals

bupropion Wellbutrin primarily for depression and smoking cessation, balances natural brain chemicals

topiramate Topamax primarily used to treat epilepsy

sertraline Zoloft primarily for depression; balances natural brain chemicals

zonisamide Zonegran primarily used to treat epilepsy

T H E E X P A N D I N G P R O B L E M O F O B E S I T Y

diabetes medications. Many popular “fad” diets lack

the support of quality research studies to prove

whether they work. However, a recent clinical trial

designed to study the effects of the Atkins diet was

led by Guenther Boden, MD at Temple University in

Philadelphia, Pennsylvania. The study revealed that the

primary reason behind the weight loss on followers of

this diet plan was a reduction of calories. See the

article on page 28 for more details.

It is clear that overweight and obesity can cause health

problems. But the results of the DPP study show that

losing weight is possible and, more importantly, losing

weight and exercising can help prevent or reverse those

health problems. However, there are some situations

in which diet and exercise are not effective at helping

people lose weight. So we ask ourselves, how is

medical science addressing the issue of weight loss?

Do combinations of drugs promote greater

weight loss than one drug alone, and are drug

combinations safe?

If more intense diet and exercise interventions are

combined with weight loss medications, will

individuals be able to lose even more weight than

current studies suggest?

How long should each drug be taken? One year?

Two years? Ten years?

Side effects of the drugs are also an important issue

and should be thoroughly discussed between patient

and medical provider before making the decision to

begin drug therapy for obesity. Some of the side

effects of the drugs discussed here included increases

in blood pressure and heart rate, gastrointestinal

symptoms (diarrhea and flatulence) and effects on

the central nervous system.

22

Review of the drug trials showed that sibutramine,

orlistat, fluoxetine, sertraline, bupropion, topiramate

and zonisamide can cause modest weight reduction of

approximately five kg (slightly more than 11 lbs) or less

after one year of use when combined with dietary

intervention. This may not seem like very much, but

when one considers that the Diabetes Prevention

Program (DPP) trial showed a medical benefit with a

mere five percent loss of body weight, weight loss

drugs may be very beneficial in helping obese

individuals reduce their risk of diabetes. The review

also revealed that among the drugs listed above,

sibutramine and orlistat have been studied the most.

In fact, GlaxoSmithKline recently reported results of a

four-year study demonstrating that weight loss with

orlistat can reduce the risk of developing type 2

diabetes in individuals with impaired glucose tolerance.

Research results published in April 2004 Diabetes Care

revealed that sibutramine significantly reduced body

weight and waist circumference as well as fasting

blood glucose and A1c levels in individuals treated with

the drug. In addition to the drugs discussed above,

the pharmaceutical company, Sanofi-Aventis, is in the

process of developing a drug known as rimonabant

(Acomplia), which is a new form of appetite

suppressant that has been shown to be quite effective

in weight loss. The company plans to file a new drug

application for Acomplia with the FDA this year and, if

successful, market the drug in 2006.

Despite the research and availability of new drugs,

there are still many questions left to be answered. The

authors of the review paper suggest that the long-term

effects of these drugs on health outcomes be studied

to ensure long-term safety as well as effectiveness.

Other questions raised included:

Surgery to Treat ObesityThe first bariatric surgery was performed in 1954 and since then the number of weight loss

surgeries has climbed along with the rate of obesity. According to a weight loss surgery review

article published in the April 5, 2005 issue of Annals of Internal Medicine, an estimated 140,000

surgical procedures for weight loss were performed in the U.S. in 2004. The study, funded

by the U.S. Agency for Healthcare Research and Quality, reviewed 147 clinical trials on the

surgical treatment of obesity including procedures known as gastric bypass, laparoscopic

adjustable gastric band technique, and biliopancreatic bypass, all of which serve to reduce

the size of the stomach and re-route the intestines in order to prevent food from being

absorbed and, as a result, promote weight loss. Results show that surgery can

result in considerable weight loss (20-30 kg or approximately 44-66 lbs) for

severely obese individuals with a BMI greater than or equal to 40, and one

study reported continued weight loss over eight years with improvements

in diabetes after surgery. Many obesity surgery studies have also shown

improvements in hypertension, dyslipidemia (a fat protein metabolism

disorder resulting in high levels of “bad” or LDL cholesterol and low

levels of “good” HDL cholesterol), and sleep apnea following surgery.

But more data are needed to determine the effectiveness and appropriateness

of each different type of surgery for different types of individuals. Complications

resulting from surgery occur in approximately 20 percent of people who undergo the

procedures, and researchers must focus on ways to reduce these complications

which can include internal bleeding or gastrointestinal problems such as vomiting or

acid reflux. Finally, research should be done to determine if surgery is effective for less

severely obese individuals.

Clearly, more work needs to be done in the area of obesity research. What we do know

is that excess fat, especially when located in the abdomen, contributes to diabetes and

cardiovascular disease and that losing weight can help decrease one’s risk for these

diseases. Whether diet and exercise, prescription weight loss medications, or surgery is

the best method for weight loss depends on the individual’s level of overweight or obesity

and their personal needs and doctor recommendation. We are fortunate that science has

brought us to the point where medication and surgery are effective weight loss options, but we

still await the day when researchers will find answers to crucial questions of long-term safety and

effectiveness of each type of therapy among different groups of people affected by obesity. ■

23

Hot Topics T H E E X P A N D I N G P R O B L E M O F O B E S I T Y

24

Research UPdates

Healthy Food Choices AwardeesThe prevalence of overweight among children and

adolescents has risen alarmingly over the past three

decades. National Health and Nutrition Examination Survey

(NHANES) data over the past 30 years has indicated the

prevalence of overweight in 6-11 year-olds has almost

quadrupled and the prevalence in 12-19 year-olds has

increased 2.5 fold. The most recent 1999-2000 NHANES

data estimates that 15 percent (almost nine million) children

and adolescents ages 6-19 are overweight. The 1999-2000

findings for children and adolescents suggest the likelihood

of another generation of overweight adults who may be at

increased risk for obesity, as well as related cardiovascular

disease and type 2 diabetes. The purpose of the Healthy

Food Choices Research Awards, funded by the ARAMARK

Charitable Fund, is to support educational, behavioral,

and nutritional outcome studies supporting a better

understanding of healthy food choices in children and

adolescents in order to prevent obesity.

The American Diabetes Association is pleased to announce

the award recipients of our newest targeted research

opportunity, the Healthy Food Choices Research Award:

Valerie Duffy, PhD, RD

University of Connecticut

Storrs, Connecticut

The Captain 5 A Day Program: Improving dietary quality

and physical activity in preschoolers

Sylvie Naar-King, PhD

Wayne State University

Detroit, Michigan

Adapting multisystemic therapy to improve food choices

and health outcomes in obese African American youth

Hollie Raynor, PhD, RD

The Miriam Hospital

Providence, Rhode Island

Changing eating behaviors in young children: Should

healthy foods be increased or unhealthy foods decreased?

A N N O U N C E M E N T S

25

A N N O U N C E M E N T SResearch UPdates

Type 1 Diabetes TrialNetThe American Diabetes Association is a proud

supporter of the federally-funded clinical trials of

TrialNet. TrialNet is a network of 18 clinical centers in

the United States, Canada, Europe, and Australia,

working together to prevent or delay type 1 diabetes.

TrialNet began thanks to a recommendation from the

Diabetes Research Working Group (DRWG), which

formed as a result of the Surgeon General’s Report,

Healthy People 2010. The goal of the DRWG was to

develop a strategic plan for diabetes research. One

recommendation of this group was to develop clinical

trials to prevent type 1 diabetes.

Two TrialNet studies are currently underway. One study

examines people at risk for type 1 diabetes (those who

have relatives with the disease) to find out how type 1

diabetes occurs. The second study uses two different

Research community loses talented, young scientist Melvin M. Denis, an American Diabetes Association Physician Scientist Award recipient, was tragically killed

in an avalanche in the mountains near Salt Lake City, Utah on December 11, 2004. Melvin was born in

Cuba and emigrated to the United States with his parents and younger sister in

1980. After earlier years of education in Florida, he was accepted to the

MD/PhD program at the University of Utah in 1999 where he was pursuing

research into vascular complications of diabetes as part of the requirements for

the combined MD/PhD degree and with support from the ADA. His studies

have resulted in reports published in the medical and scientific literature, and he

will ultimately be awarded the PhD degree posthumously from the University of

Utah. All who knew him agree that Melvin would have made an outstanding

physician-investigator and that he brought great joy and empathy to the healing

professions and to those around him. ■

medications to prevent the destruction of beta cells in

patients newly diagnosed with type 1 diabetes. TrialNet

is funded by the National Institute of Diabetes &

Digestive & Kidney Diseases (NIDDK) through the Type

1 Diabetes Special Statutory Funding Program which

commits $1.14 billion for type 1 diabetes research from

1998-2008. This funding is an addition to the regularly

appropriated funds received by the Department of

Health and Human Services (HHS) for diabetes

research. The National Institute of Child Health and

Human Development (NICHD), the National Institute

of Allergy and Infectious Diseases (NIAID) and the

American Diabetes Association are also sponsors of

this initiative.

To read more about TrialNet, visit the study’s website at

www.diabetestrialnet.org. ■

26

American Diabetes Association funded researcher publishes new bookbasic steps for receiving good care and

sustaining that care.”

Dr. Peters’ Clinical Research Award, What are the

factors associated with sustained global risk reduction

in an underserved Latino population treated in a

diabetes disease management program?, ties in

well with the theme of her book. Her ADA study,

performed in East Los Angeles, looks at parameters

associated with better outcomes among Latinos with

diabetes. The goal of her study is to determine what

tools and education people need to not only achieve,

but maintain good health outcomes throughout their

lives. Her book includes photos and first-person

accounts from patients explaining that it is possible

to prevent diabetes and treat diabetes well.

Dr. Peters is happy to see her patients participate

in their care and control their diabetes. “I see great

outcomes every day.” ■

Anne Peters, MD, former chairperson of the American

Diabetes Association Council on Health Care Delivery

and Public Health and an ADA Clinical Research Award

recipient, recently published the diabetes care book,

“Conquering Diabetes: A Cutting-Edge, Comprehensive

Program for Prevention and Treatment.” The book

gives an overview of pre-diabetes, type 1, type 2 and

gestational diabetes, explains the various drug

treatment options available to people with diabetes,

and stresses the importance of diet and exercise in

both treating and preventing diabetes. Dr. Peters is a

professor of clinical medicine at the University of

Southern California (USC) Keck School of Medicine,

and Director of the USC Clinical Diabetes Program.

“The reason I wrote this book,” Dr. Peters explains,

“is because I see patients every day who do not have

good control of their diabetes even though they see

doctors. They don’t know what to ask and don’t know

what good care should be. This book describes the

Research UPdates I N T H E N E W S

American Diabetes Association past president authors book on diabetes and obesity crisis The New York Times reported in April 2005 that

Francine Kaufman, MD, American Diabetes Association

past president and research grant recipient, authored

the book “Diabesity: The Obesity-Diabetes Epidemic

That Threatens America — and What We Must Do to

Stop It” (Bantam). The article reports that Dr. Kaufman

is treating an increasing number of children and

adolescents for type 2 diabetes, due in large part to the

growing rate of obesity in this population. She credits

this rise in diabetes and obesity to the convenience and

low cost of unhealthy fast food, a shortage of healthy

foods in school cafeterias and vending machines, and

a lack of exercise among our nation’s youth. Dr.

Kaufman stresses that offering children more healthful

foods and encouraging them to exercise in school and

in safe areas in their neighborhoods will help our

nation’s young people to reduce their chances of

getting diabetes. Dr. Kaufman explains, “I wrote this

book to bring a face to the diabesity epidemic. My

book contains stories of people touched by diabetes,

interspersed with the facts that support the gravity of

the epidemic. I wrote it as a call to action so that we

can each examine how we live our lives and what we

must each do to improve the environment where we

work, where we live, and where our children go to

school so that we might start to advocate for change.”

Dr. Kaufman is a Professor of Pediatrics at the

Children’s Hospital Los Angeles, and was principal

investigator of the National Institute of Diabetes &

Digestive & Kidney Diseases (NIDDK)-funded Diabetes

Prevention Trial of Type 1 Diabetes (DPT-1), to prevent

type 1 diabetes from developing in individuals at high

risk for the disease. She is now chair of the Studies to

Treat or Prevent Pediatric Type 2 Diabetes (STOPP-

T2D) steering committee. The STOPP-T2D trials are

funded by NIDDK and supported by the American

Diabetes Association. The trial is scheduled to begin in

Fall 2005; however, the treatment trial, Treatment

Options for Type 2 Diabetes in Adolescents and Youth

(TODAY), is currently underway at 12 medical centers

around the U.S. The purpose of the TODAY trial is to

study the safety and effectiveness of three different

treatments for type 2 diabetes in young people. To

read more about the TODAY trial, visit their website at

www.todaystudy.org. ■

27

Francine Kaufman, MD

28

A March 2005 article by the Philadelphia Inquirer reported

that ADA-funded investigator Guenther Boden, MD of

Temple University recently concluded the first clinical trial

to study the effects of the Atkins diet in a controlled

hospital setting. During the study, 10 obese patients

with type 2 diabetes followed the Atkins diet for two-

weeks, limiting their carbohydrate intake to 20 grams

per day while being offered unlimited amounts of protein

and high fat foods. While on the reduced carbohydrate

diet, the patients spontaneously reduced their caloric

intake by 1,000 calories per day and lost an average of

four pounds each over the two-week period with at least

one patient losing 18 pounds in two weeks. According

to Dr. Boden, the patients were not bored with the food

selection, and weight loss was not due to water loss or

a change in metabolism, but simply due to a reduction

in the number of calories consumed. In addition to the

weight loss, the patients who participated in the study

also experienced improved glucose levels and insulin

sensitivity which allowed

some of them to reduce

their diabetes medications.

They also experienced

lower triglyceride and

cholesterol levels. In Dr.

Boden’s study, published in

the Annals of Internal

Medicine, he concludes

that the patient’s excessive overeating was fueled by

carbohydrates. He warns, however, that the long-term

effect of low-carbohydrate diets is unknown. This diet

also had a low fiber content which may also lead to

health problems if continued over time. (Boden G,

Sargrad K, Homko C, Mozzoli M, Stein TP. Effect of a

low-carbohydrate diet on appetite, blood glucose levels,

and insulin resistance in obese patients with type 2

diabetes. Annals of Internal Medicine. Mar

15;142(6):403-11, 2005). ■

New study reveals reason behind Atkins weight loss

Guenther Boden, MD

New drug approved for use in type 2 diabetes

In the Winter/Spring 2005 issue of Forefront, we reported that researchers were investigating a new

drug called exenatide in people with type 2 diabetes. The drug, a synthetic version of a hormone found

in the saliva of the Gila monster, stimulates insulin secretion in humans. Amylin

Pharmaceuticals, Inc. and Eli Lilly and Company have just announced that

the U.S. Food and Drug Administration has approved exenatide in an

injectable form to help control blood sugar in type 2 diabetes patients

who are unable to achieve optimal control using oral

medications (metformin and/or a sulfonylurea). Byetta

(pronounced bye-A-tuh), the trade name for exenatide, is

the first in a new class of medicines known as incretin

mimetics. Byetta will be available in June 2005. ■

29

I N T H E N E W SResearch UPdates

RxPGNews.com reported that the

first American Diabetes Association

Islet Cell Summit was held on April 8

in Chicago, Illinois. At this invitation-

only event, recipients of the American

Diabetes Association’s Islet Cell

Replacement Research Awards

shared their latest findings on insulin-

producing cell replacement in type 1

diabetes with donors who have

supported their work, as well as invited

guests who had expressed an interest

in funding diabetes research through

the American Diabetes Association.

The ADA Islet Cell Replacement

Research Awards are funded in

part by Cynthia and Edsel B.

Ford, II of Grosse Pointe,

Michigan and Arleen and Don

Wagner of Venetia, Pennsylvania.

These families have generously

committed gifts of $1.3 million

and $1 million, respectively, to

support the study of islet cell

replacement. Both families

became involved with raising

funds for the Association after

their children were diagnosed

with type 1 diabetes. In addition

to their financial support, these

families have also contributed

countless hours as volunteers for the

Association. Currently, Arleen Wagner

serves as President of the ADA's

Washington County, Pennsylvania

Council, Don Wagner is Chair of the

ADA Research Foundation, Cynthia

Ford is a member of the ADA

Research Foundation Board of

Directors, and Edsel Ford chairs the

Advisory Board of ADA’s Advocacy

Leadership Council. The seven

researchers who presented at the

Summit are Charles Burant, MD,

PhD, University of Michigan; Juan

Domínguez-Bendala, PhD, on behalf

of Luca Inverardi, MD, Diabetes

Research Institute at the University of

Miami, Leonard M. Miller School of

Medicine; Hengjiang Dong, PhD,

Children’s Hospital of Pittsburgh;

Marc Garfinkel, MD, University of

Chicago; Michael German, MD,

University of California, San

Francisco; Paul Robbins, PhD,

University of Pittsburgh, and Ji-Won

Yoon, PhD, Rosalind Franklin

University of Medicine and Science.

Participants heard updates on the

scientists’ ongoing work which reflects

one of three major focus areas:

• Genetic engineering of non-

pancreatic cells into glucose-

sensitive, insulin-producing cells;

• Transforming stem cells or

pancreatic ductal cells into insulin-

producing cells; and,

• Micro-encapsulation of islet cells to

restore normal glucose levels in

people with diabetes, with particular

focus on preventing rejection of

these islets by the immune system.

The American Diabetes Association’s

targeted research program allows

donors to specify the type of

research they wish to fund. The

Summit was a great way for

contributors to see firsthand how

their generosity is advancing

diabetes research in the area

they specified. It was also an

opportunity for the researchers to

share their ideas with one another.

“As parents of a child with type 1

diabetes, we have personally

invested in these scientists and

their promising research, knowing

that their work brings us one step

closer to life without diabetes for

all those afflicted,” said Don and

Arleen Wagner. “This summit

provides a unique opportunity to talk

with and learn from those individuals

who are truly making a difference.” ■

First Islet Cell Summit brings together researchers and donors

Human islet. Courtesy of Steven Kahn, MB, ChB,Seattle Institute for Biomedical and Clinical Research

Low birth weight linked to type 2 diabetes

A February 2005 MSNBC article

reports that Mary Elizabeth Patti, MD,

a researcher at the Joslin Diabetes

Center in Boston, has discovered

that low birth weight permanently

alters the function of insulin-

producing cells in the pancreas, thus

contributing to the development of type 2 diabetes later

in life. In her ADA funded Research Award, Molecular

determinants of low birth weight-associated diabetes, Dr.

Patti studied two groups of pregnant mice. She gave the

first group of pregnant mice all the food it wanted during

their three-week pregnancy while restricting the diet of the

second group of mice during the final week of pregnancy.

The babies born to the food-restricted mothers weighed

23 percent less than the babies born to mothers who

were not food-restricted. Dr. Patti then compared the low

birth weight baby mice to normal weight baby mice. Both

groups of baby mice were fed the same diet; however,

the low birth weight baby mice showed abnormally high

levels of blood glucose as they matured. Results from

her study revealed that the cells of the pancreas in the

low birth weight mice were not able to produce insulin in

the appropriate amounts. Even when the mice reached a

normal weight, this impairment was not resolved. Low

birth weight is also a risk factor for type 2 diabetes in

humans. Therefore, the results of this study emphasize

the need for individuals of low birth weight to focus on

diabetes prevention, including weight maintenance and

physical activity. It also demonstrates the importance of

good prenatal nutrition in preventing health complications

later in life. (Jiminez-Chillaron JC, Hernandez-Valencia M,

Reamer C, Fisher S, Joszi A, Hirshman M, Oge A,

Walrond S, Przybyla R, Boozer C, Goodyear LJ, Patti

ME. Beta cell secretory dysfunction in the pathogenesis

of low birth weight-associated diabetes. Diabetes.

54(3):702-711, 2005). ■

30

Researchers make strides in stem cell research

ADA funded investigators Luca

Inverardi, MD and Ricardo

Pastori, PhD collaborated with

Juan Domínguez-Bendala, PhD

at the Diabetes Research

Institute at the University of

Miami Leonard M. Miller School

of Medicine in Miami, Florida to discover a new way to

encourage embryonic stem cells to turn into islet cells.

The Miami Herald reported in March 2005 that this team

successfully used a new technique to encourage mouse

embryonic stem cells to become islet cells. Before a

stem cell can become an islet cell, it must be able to

produce certain proteins in a particular sequence. One of

the road blocks in stem cell research involves the difficult

task of getting stem cells to produce these proteins

correctly. However, the group at the Diabetes Research

Institute was able to get around this dilemma by using a

technique that delivers the necessary proteins directly to

the stem cell. After delivering the proteins to the mouse

stem cells, their differentiation into islets was strongly

stimulated. The next step is to produce these same

results using human cells, which is already underway.

(Domínguez-Bendala J, Dagmar K, Ribeiro M, Ricordi C,

Inverardi L, Pastori R, Edlund H. TAT-mediated

neurogenin 3 protein transduction stimulates pancreatic

endocrine differentiation in vitro. Diabetes. 54(3):720-726,

2005). ■

Luca Inverardi, MDMary Elizabeth

Patti, MD

Research UPdates N O T E W O R T H Y A D V A N C E S

Protein found to prevent atherosclerosis

Louis Ragolia, PhD of Winthrop University Hospital

and Stony Brook University in New York is working

to prevent atherosclerosis, or a thickening of the

artery walls, in people with diabetes. Dr. Ragolia

was named the first Thomas R. Lee Award winner

for his ADA Career Development Award, The

molecular basis of vascular smooth muscle cell

apoptosis, which began in 2002. The Thomas R.

Lee Award goes to the Career Development Award

applicant who receives the best peer-reviewed score

on his/her application in a given fiscal year. The

award not only recognizes excellence in diabetes

research, but also signifies the ADA’s belief that the

recipient will continue to be a premier researcher

who will have great impact in diabetes treatment,

prevention or the search for a cure. Dr. Ragolia’s

recent research results have proven him worthy of

this award. His research has shown that a protein

found in blood, called L-PGDS, can prevent

inflammation and control the thickening of arteries

by regulating the growth of artery wall cells. He also

found that L-PGDS can prevent the movement or

“migration” of artery cells, an event which can lead

to formation of plaques in the arteries. Finally, Dr.

Ragolia found that the cells of mice with diabetes

react differently to L-PGDS than the cells of mice

without diabetes, and it appears that L-PGDS may

reverse insulin resistance in diabetes. Dr. Ragolia

will continue to study how the cells of animals with

diabetes react to L-PGDS and future studies will

involve development of methods or drugs to correct

the reaction. ■

Louis Ragolia, PhD

31

32

C. Ronald Kahn, MD and medical student Cullen

Taniguchi funded by an American Diabetes Association

Medical Scholars Award at Joslin Diabetes Center in

Boston, Massachusetts, found that lowering the level of

two key proteins in the liver can cause type 2 diabetes.

By using new genetic engineering tools, they were able

to turn off the two specific cellular signaling proteins

(IRS-1 and IRS-2) in the liver. They also designed

separate experiments and found that low levels of IRS-1

cause liver cells to make more glucose and blood sugar

levels to rise. Low levels of IRS-2 are linked to high

levels of blood fats such as triglycerides. When both

IRS-1 and IRS-2 are low, diabetes occurs. Now that

researchers have discovered that these two factors are

involved in type 2 diabetes, more research can be done

to determine how to keep levels of IRS-1 and IRS-2 up.

(Taniguchi CM, Ueki K, Kahn CR. Complementary roles

of IRS-1 and IRS-2 in the hepatic regulation of

metabolism. Journal of Clinical Investigation, 2005

March 1; 115(3): 718–727.) ■

The Winter/Spring 2005 issue of

Forefront reported that Steven

Shoelson, MD, PhD and Dongsheng

Cai, MD, PhD discovered that a

factor known as NF�B contributed

to muscle wasting in mice. They

also found that drugs known as

salicylates stopped NF�B and

helped the mice regain their muscle

mass. A new study by Drs. Shoelson

and Cai published in the February

2005 issue of Nature Medicine

reports on a new discovery about

NF�B.

Researchers are aware that obese

people have livers which accumulate

fat quickly, and that many overweight

individuals with type 2 diabetes have

high levels of NF�B in their livers.

Dr. Shoelson and his team found

that in obese mice with fatty livers,

NF�B was activated and caused low

levels of inflammation. They then

studied lean mice without diabetes

by turning on the gene that

expresses NF�B, and looking for

signs of inflammation. The result

was that the lean mice showed low

levels of inflammation as well as high

insulin and blood glucose levels. By

triggering NF�B to cause low-level

inflammation, they were able to

cause diabetes in mice that were

not at risk for the disease.

As in their muscle wasting study, Dr.

Shoelson and Dr. Cai decided to try

using salicylates to reduce the

inflammation, and were successful.

Dr. Shoelson is currently working

with the NIH to fund a large-scale

national trial to study the use of mild

salicylate drugs in people with

diabetes. (Cai D, Yuan M, Frantz

DF, Melendez PA, Hansen L, Lee J,

Shoelson SE. Nature Medicine, Feb

11(2):183-90, 2005). ■

Two key liver signals shown to cause type 2 diabetes

Researchers discover diabetes trigger and potential treatment

Cullen Taniguchi and C. Ronald Kahn, MD

Dong Sheng Cai, MD, PhD andSteven Shoelson, MD, PhD

33

Message from the American Diabetes AssociationResearch Foundation Chair

The day you learn your young, helpless child has type 1 diabetes, you start on a journey of

transformation. What begins as a frightening, lonely experience can turn into an

amazing, self-empowering, golden opportunity for positive change if you know where to

turn for the skills, knowledge and hope that diabetes requires for living well.

Our journey as parents of a child with type 1 diabetes led us to join our local American Diabetes Association office in 1986.

For years, we have paid close attention to new developments in diabetes care which profoundly improved our daughter’s

quality of life to the extent that she is now married and has a healthy child of her own. By finding new ways to fight

diabetes, everyone is encouraged to work harder and it is research that makes these improvements in treatments possible.

Today, I and my wife, Arleen, continue to be involved locally and nationally with the ADA. Naturally, we are drawn to

research and have often discussed state-of-the-art diabetes research with some of the world’s most prominent scientists

funded by the ADA Research Foundation. We know that we are making remarkable progress, yet our work is far from over.

While the federal government is doing what it can to fund diabetes research, it is not doing enough to keep up with the

widespread growth of the fastest developing, chronic disease of our time. This adds greater urgency to the work of the

American Diabetes Association and our Research Foundation.

Founded in 1994, the ADA Research Foundation was created to accelerate the Association's ability to raise major gifts to

directly fund diabetes research. To date, the Foundation has contributed more than $46 million to diabetes research and

has single-handedly transformed the breadth and depth of the ADA Nationwide Research Program, giving it greater

prestige and purpose and, above all, its unique ability to match a donor's interests and dollars with leading-edge diabetes

research projects. On page 15, you’ll find an excellent example of inspiring, donor-driven research funded by California

philanthropists, Terry and Louise Gregg.

Recently, the Research Foundation was also responsible for bringing together seven of the world’s most accomplished type

1 diabetes researchers to brief donors on their progress at our first Islet Cell Summit held this past spring in Chicago.

Donors saw firsthand the powerful impact their support is making in helping researchers develop replenishable sources

of cells that could restore the body’s ability to produce insulin.

Philanthropy has always played the most prominent role in supporting the ADA’s commitment to life without diabetes—

so much so that we feel empowered to reach our $300 million goal by 2010 if that’s what it takes to defeat diabetes in our

lifetime. Please join us in our journey toward life without diabetes. To learn more about donor-driven research projects

or any aspect of the Research Foundation, Pinnacle Society or Summit Circle, please contact Ms. Elly Brtva, Managing

Director of Individual Giving at (800) 676-4065, ext. 4377 or ebrtva@diabetes.org. Thank you for your ongoing support.

Sincerely,

Don Wagner

34

1-800-DIABETES

IndividualGiving@diabetes.org1701 N. Beauregard Street

Alexandria, VA 22311

Did you know?

• Of the 18.2 million Americans with diabetes, it is estimated that 5.2 million of

them do not even know they have the disease.

• Another 41 million Americans have pre-diabetes, a condition in which blood

sugar levels are higher than normal but not quite high enough for a diagnosis

of diabetes. People with pre-diabetes are at increased risk for developing diabetes.

• To date, the American Diabetes Association has invested more than

$350 million in diabetes research throughout the nation.

• The Association places a strong emphasis on supporting young scientists

and providing training awards to new, talented researchers who benefit from

receiving a young investigator award before moving on to obtain larger grants.

The American Diabetes Association’s

Annual Scientific Sessions is the largest

annual research and clinical meeting on

diabetes. This year’s annual meeting

was held June 10-14, 2005 in San

Diego, California. To find out more

about the scientific information

presented at the meeting, log on to

www.scientificsessions.diabetes.org

June 10-14, 2005 • San Diego, CaliforniaJune 10-14, 2005 • San Diego, California