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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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2
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.”
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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
cavo
ne P
hoto
grap
hy
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 [email protected]. Thank you for your ongoing support.
Sincerely,
Don Wagner
34
1-800-DIABETES
[email protected] 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