Mr. Chairman, I am Phillip Gorden, the Director of the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK), which has lead responsibility for diabetes
research at the National Institutes of Health (NIH), within the Department of Health and
Human Services. I appreciate the opportunity to testify before this Subcommittee about NIH
research to understand, treat, prevent, and ultimately cure diabetes.
In both human and economic terms, diabetes is an extremely costly disease. It affects
an estimated 16 million Americans, including both genders, the young and the old, all
races and ethnic groups, the rich and the poor. Consistent with the focus of todays hearing, I will
address my testimony toward diabetes in children, who, in many ways, suffer most from the
disease. They have the disease from an early age and must endure lifelong treatment. They
must carefully adjust what they eat and everything they do--from schoolwork to sports--in
order to manage their disease. Even with a continuous struggle to follow such rigorous
regimens, they may still develop serious, long-term complications of diabetes.
Children with type 1 diabetes must have daily insulin injections to survive. They and
their families must monitor their blood glucose levels throughout the day. While the value
of maintaining blood glucose control is clear, this therapy is extremely difficult, and
must be made better and easier for everyone.
Based on case reports and clinic-based studies, new information is emerging about
children with type 2 diabetes. It appears that these children are not dependent upon
insulin injections; however, their cells and tissues are resistant to insulin. Some may
require insulin to maintain control of their blood glucose. The number of children with
type 2 diabetes is increasing in our population and the age of onset is now occurring
earlier. This is a special problem in racial and ethnic minority populations, who suffer
disproportionately from diabetes, as well as from obesity--a major risk factor for type 2
diabetes. In most cases, type 2 diabetes in children appears as a complex, polygenic
disease similar to that seen in adults. The NIDDK will be bringing together pediatric
endocrinologists from across the U.S. to share information on the emerging problem of type
2 diabetes in children.
HIGHLIGHTS OF NIH-WIDE RESEARCH EFFORTS AND STRATEGIES
I would like to emphasize several points that are central to present and future efforts
to treat diabetes effectively and ultimately cure it. The many institutes and centers of
the NIH have a broad and multifaceted research agenda to treat, prevent and cure diabetes.
The trans-NIH diabetes effort has led to major clinical advances in diabetes, and clues in
the search for a real cure. We are witnessing rapid advances in genetics and genomics that
underlie our goal to find and eliminate the cause of many diseases, including diabetes.
Discoveries of mechanisms to manipulate the immune system have significant implications
for diabetes prevention and treatment. Major new understandings of cell communication are
critical to diabetes. Key advances in clinical research are showing how the control of
blood pressure and serum cholesterol, as well as other lipids, is important in the
comprehensive care of patients with diabetes.
The Diabetes Control and Complications Trial (DCCT) demonstrated that the complications
of diabetes affecting the eye, kidney and nerves can be ameliorated or prevented. These
results have been extended by the clinical progress achieved in treating diabetic eye
disease with photocoagulation, and the use of drugs--such as ACE inhibitors--for the
kidney disease of diabetes. Together, these advances represent major steps forward in our
continued quest for a cure. However, they also further emphasize the compelling need to
develop better technologies both to manage blood glucose levels and to treat complications
more effectively and directly.
In the past decade, investigators supported by the NIDDK, the National Institute of
Child Health and Human Development (NICHD), and the National Institute of Allergy and
Infectious Diseases (NIAID) have been able to establish immune, metabolic, and genetic
screening tests to identify individuals at high risk for developing type 1 diabetes. In
animal models and in preliminary human trials, researchers have also shown that low-dose
insulin therapy may prevent or delay the onset of the clinical manifestation of type 1
diabetes. Thus, scientists can identify individuals at high risk for type 1 diabetes and
intervene with a safe and possibly effective therapy. These tools are now being applied in
a major multi-center clinical trial cosponsored by the NIDDK, NIAID, NICHD, the Juvenile
Diabetes Foundation International (JDF) and the American Diabetes Association to prevent
or delay the onset of type 1 diabetes. This trial is called the Diabetes Prevention
Trial-1, or DPT-1. Another clinical trial, "Prevention of Cardiovascular Disease in Diabetes," will generate knowledge
that will be important for preventing heart and vascular disease in early onset type 1, as
well as type 2 patients. The National Heart, Lung, and Blood Institute (NHLBI) is
sponsoring this trial, in conjunction with the NIDDK.
We at the NIH join the children and families touched by diabetes in a shared effort to
support vigorous, promising research aimed at the prevention, treatment and cure of this
disease and have been pleased to collaborate with voluntary organizations, such as the
JDF, in fruitful research partnerships.
To guide our diabetes research programs, we have sought the best advice possible from
the scientific and voluntary diabetes community. For example, we have accelerated and
enhanced our efforts based on a special trans-NIH workshop, entitled "iabetes Mellitus:
Challenges and Opportunities" -- complemented by the Strategic Plan of the Diabetes Research
Working Group. We have already initiated many recommendations from these processes and
will continue to build upon them in the future. I am pleased to share with you today some
of our most recent efforts, which relate to diabetes in children. A number of these have
been undertaken in partnership with other NIH Institutes, other agencies, and voluntary
SPECIAL INITIATIVE ON TYPE 1 DIABETES
I am pleased to report progress on a special, NIH-wide initiative for innovative,
clinically relevant and multidisciplinary research aimed at the treatment and cure of type
1 diabetes. This initiative is relevant to all of the scientific opportunities in type 1
diabetes research today, but especially to the development of more effective therapies,
which can be easily administered and followed. Through this initiative, we are seeking the
best research talent from diverse fields, the most promising research ideas, and the most
technologically advanced research tools for combating type 1 diabetes. We are exploiting
the fruits of the biotechnology revolution, with special attention to clinical issues.
Initiatives have been launched to develop therapies to achieve normal glucose levels in
people with type 1 diabetes and to develop improved glucose sensors for regulating blood
glucose. They also include expanded programs to understand the mechanisms by which high
glucose levels result in the late complications of diabetes; to apply this information to
the development of ways to prevent, limit or reverse complications associated with
diabetes; and to understand the role of factors important in disease development.
This year special funds for type 1 diabetes research appropriated in the Balanced
Budget Act of 1997 are being used to focus on the mechanisms by which the disease results
in painful and disabling neuropathies and other neurological complications; identification
of stem cells and factors that regulate development and differentiation of pancreatic beta
cells through the establishment of a functional genomics resource in diabetes; and pilot
studies for new therapies for type 1 diabetes and its complications.
INITIATIVE ON CELL-BASED THERAPIES FOR TYPE 1 DIABETES
We are embarking on a new and exciting initiative to restore insulin-producing capacity
through transplantation of the whole pancreas, or of islets from the pancreas. This
research is being propelled by an impressive series of advances. Recent studies in
primates have shown that both insulin-producing islet cells and kidneys can be
transplanted using a highly selective method to control for immune rejection of the
transplant. This new technology involves what is referred to as "blockade of the
co-stimulatory pathway." It allows for a selective form of immune tolerance and does not
require suppression of the overall immune system, as is required by conventional therapy
for organ transplantation.
Paralleling this initiative is a major, new, collaborative effort on immune tolerance
within the intramural program of NIH. The research partnership involves the NIDDK, the
Warren Grant Magnuson Clinical Center, the Department of Defense, and the Diabetes
Research Institute of the University of Miami. The strategy under study is relevant to
both the treatment of type 1 diabetes and kidney transplantation. Furthermore, there is a
major, additional joint effort involving NIDDK, NIAID and the JDF to broaden this program
into a network of collaborating institutions.
INITIATIVE TO ENHANCE MODALITIES OF TREATMENT
We are working diligently to develop a wide range of new and more effective therapies
for avoiding the consequences of low blood glucose levels and for improving the treatment
of diabetes. For example, the NICHD is supporting two comprehensive studies in adolescents
on how low blood glucose levels affect learning skills and how the undesirable effects of
multiple daily insulin injections affect compliance. We are also pioneering the
development of glucose sensors and mechanical systems to facilitate insulin administration
and thus ease the burden of this therapy for children and adults who are
One exciting recent advance may well have important therapeutic implications with
respect to the immune systems attack on its own insulin-producing cells in type 1 diabetes.
Researchers have shown that a protein called GAD, which is expressed by beta cells,
controls the development of diabetes in an animal model of human type 1 diabetes. The
demonstration that this protein initiates autoimmune diabetes builds on an earlier
NIH-supported advance, which showed that cells specifically reactive against GAD directly
produced beta cell injury in a mouse model. This avenue of research could have important
consequences for the development of new therapies to prevent type 1 diabetes, provided
these findings can be extended to human disease.
We also hope that new clinical advances will emerge from other NIH-supported
investigations of pancreas and islet transplantation in animals. This work includes
studies on ways to regenerate the pancreas; to develop methods to enable the protection
and survival of implanted insulin-producing cells; and to discover innovative approaches
to prevent graft rejection by induction of immune tolerance.
INITIATIVE ON PREVENTION AND TREATMENT OF COMPLICATIONS
Multiple NIH institutes are participating in a major initiative to combat the eye,
nerve, kidney and vascular system complications of diabetes. These efforts include the
search for genes that make individuals with diabetes particularly susceptible to
developing one or more of these complications. Also featured is a new emphasis on
understanding and treating diabetic nerve disease, and the inauguration of a major
clinical trial aimed at reducing the cardiovascular complications of diabetes. These
research areas have been identified as having high priority by the Diabetes Research
INITIATIVE FOR DIABETES CLINICAL TRIAL NETWORK
One of the recommendations of the Diabetes Research Working Group is to establish a
Diabetes TrialNet to foster clinical studies. In response, the NIDDK recently provided
administrative extensions to the centers involved in the ongoing DPT-1, while a task force
considers approaches for establishing such a network for future studies of prevention and
treatment of type 1 diabetes. A component of this initiative will probably include support
for the infrastructure for clinical researchers and nurses to conduct research; a central
data coordinating center; central laboratories; mechanisms to review and prioritize
research projects; and, databases of research volunteers, investigators and projects. Such
a diabetes clinical research network would provide the necessary infrastructure for the
efficient, rapid evaluation of promising new therapeutic approaches.
In closing, I would like to mention just two examples of the many beneficial research
collaborations between the NIH and voluntary health organizations, such as the JDF. The
NIDDK-JDF centers of excellence program represents a productive research partnership and a
model that has been adapted by several other NIH institutes. Also, the JDF and the NICHD
are now co-funding a study of 12,000 infants who are at various levels of genetic risk for
type 1 diabetes in order to detect the earliest evidence of immune attack on the insulin
producing cells of the pancreas. These examples reflect the strong relationships the NIH
and voluntary health organizations have formed to accelerate research progress.
Mr. Chairman, I am grateful for the opportunity to share with you recent and exciting
NIH efforts focusing on diabetes in children. I have tried to emphasize today that we at
the NIH truly understand the great burden diabetes places on families. At the same time, I
want to share my feelings of great encouragement and hope because of the pace at which
diabetes research is moving. I believe that our strong national research programs hold the
essential key to curing this disease for the benefit of all children and their families. I
am pleased to answer any questions you may have.