|Plan Will Guide NIH Research in Type 1 Diabetes
The National Institutes of Health (NIH) has released a long range
plan that will help to guide research in type 1 diabetes for the
next decade. Advances and Emerging Opportunities in Type 1
Diabetes Research: A Strategic Plan [http://www.T1Diabetes.nih.gov/plan]
identifies goals and objectives to exploit recent scientific advances
in combating this autoimmune form of diabetes.
About 5 to 10 percent of the nearly 21 million people with diabetes
have type 1, formerly known as juvenile onset diabetes or insulin-dependent
diabetes. In this form of diabetes, immune cells attack and destroy
pancreatic beta cells, which produce the critical hormone insulin
needed for survival. Type 1 diabetes tends to arise in children
and young adults, who need three or more insulin injections a day
or treatment with an insulin pump to maintain blood glucose control.
To prevent complications they must regularly monitor their blood
glucose, striving for a range that is as close to normal as possible.
The constant challenge of managing the disease poses a serious
burden for patients and their families.
Type 1 diabetes cuts lives short by about 15 years, with early
deaths due mainly to heart attacks and strokes. However, research
has made dramatic progress in extending life expectancy for people
with this disease. A recent study found that 20 percent of people
born in the 1950’s died within 20 years of a type 1 diabetes diagnosis,
and 30 percent died within 25 years of diagnosis. For people born
between 1975 and 1980, however, 3.5 percent died within 20 years
of diagnosis, and 7 percent died within 25 years.
“Research has greatly improved the length and quality of life
of people with type 1 diabetes, and it has lowered the risk of
developing certain serious complications, such as retinopathy and
kidney failure. However, many challenges remain in combating this
complex autoimmune disease. The NIH Strategic Plan sets forth a
cogent, multifaceted approach to future research that soundly addresses
these challenges,” said NIH Director Elias A. Zerhouni, M.D.
The Plan describes scientific advances resulting from type 1 diabetes
research and outlines specific objectives to further the following
1. Identify the genetic and environmental causes of type
Both genetic susceptibility and one or more environmental triggers
contribute to the development of type 1 diabetes. Genes that confer
varying degrees of risk have been identified, but researchers continue
to search for others. Finding all the genes will boost the ability
to predict who is at risk and foster prevention efforts. Because
many people with high-risk genes don’t develop type 1 diabetes,
scientists believe environmental factors — perhaps toxins,
infectious agents, or components of the diet — also play
a role. Several groups, including the International Type 1 Diabetes
Genetics Consortium and The Environmental Determinants of Diabetes
in the Young (TEDDY), are working to identify all the genetic and
environmental factors that lead to diabetes. The outcome of their
work could have enormous benefits, such as a preventive vaccine
against an infectious trigger or a dietary change that averts autoimmunity
and diabetes onset.
2. Prevent or reverse type 1 diabetes
Researchers have made great strides in understanding, detecting,
and monitoring autoimmunity and now have better tools to study
the early stages of type 1 diabetes. Testing for genetic susceptibility
and autoantibodies, they can identify who is at high, moderate,
and low risk for developing type 1 diabetes. They also have a
better grasp of the immune events that lead to the destruction
of beta cells. Several studies now point to insulin itself as
the target of immune cells. Clinical trial groups, including
the Type 1 Diabetes TrialNet and the Immune Tolerance Network,
are currently testing ways to modulate the immune system to prevent
type 1 diabetes and to arrest the autoimmune attack in people
with newly diagnosed diabetes, who still have some functioning
3. Develop cell replacement therapy
Since 2000, when researchers at the University of Alberta in Edmonton,
Canada, pioneered a new method for transplanting islets, or clusters
of beta cells, researchers have been steadily refining the procedure
for people with severe complications from type 1 diabetes. Islet
transplantation improves glucose control and alleviates hypoglycemia
unawareness, which afflicts some people with longstanding type
1 diabetes. However, the side effects of immunosuppressive drugs,
which prevent the body’s rejection of donor islets, have limited
the procedure to people with hypoglycemia unawareness or those
already taking immunosuppressive drugs after a kidney transplant.
Researchers seek to overcome the remaining barriers to islet
- developing methods to produce an unlimited supply of islets
- improving ways to harvest islets
- reducing complications of islet transplantation, and
testing ways to prevent recurrent autoimmunity and the immune rejection
of donor islets.
To address the inadequate supply of donor islets, the Beta Cell
Biology Consortium is exploring beta cell development and regeneration
with the goal of growing unlimited numbers of beta cells. Other
projects include a registry that tracks the outcomes of islet transplants
and a research group that is testing ways to induce immune tolerance
in non-human primate models of kidney and islet transplantation.
4. Prevent or reduce hypoglycemia in type 1 diabetes
Major clinical studies have clearly shown that intensive glucose
control dramatically delays or prevents the eye, nerve, kidney,
and heart complications of type 1 diabetes. The main barrier
to tight control is hypoglycemia, which occurs when insulin causes
blood glucose to fall too low. Some patients with difficult-to-control
diabetes cannot sense falling blood glucose and lose consciousness
without warning. Recently approved continuous glucose monitors
developed with NIH support are helping patients control their
glucose levels more easily. This revolutionary technology is
the first step in the path to develop an artificial pancreas.
Current studies are also focusing on how the brain senses hypoglycemia
and controlling hypoglycemia through behavioral therapy.
5. Prevent or reduce the complications of type 1 diabetes
Together, diabetes and high blood pressure account for 72 percent
of all new cases of kidney failure. After 20 years of annual
increases from 5 to 10 percent, rates for new kidney failure
cases have leveled off. The most encouraging trend is in diabetes,
where rates for new cases in whites under age 40 are the lowest
in 20 years. Improved control of glucose and blood pressure and
the use of anti-hypertensive drugs called ACE inhibitors and
ARBs prevent or delay kidney failure. With good care, fewer than
10 percent of people with diabetes now develop kidney failure.
Scientists have made great progress in preventing and treating
the eye damage of diabetes. With laser treatment and vitrectomy,
blindness has been reduced by 90 percent in patients with severe
diabetic retinopathy. NIH researchers discovered that a protein
called vascular endothelial growth factor (VEGF) spurs the development
of abnormal blood vessels that invade the retina to cause blindness.
NIH-sponsored clinical studies are now testing drugs that control
the development of new blood vessel growth in the eye.
Advances in understanding how high blood glucose causes damage
to cells and tissues have led to several promising drugs that are
ready for testing in clinical trials to treat and prevent complications.
The Strategic Plan stresses the need to further clarify these pathways
by studying the role of genetic factors and applying the tools
of systems biology.
6. Attract new talent and apply new technologies to research
on type 1 diabetes
Engaging talented scientists from diverse disciplines is critical
to the success and future of diabetes research. The NIH is vigorously
pursuing this goal in different ways, e.g., by encouraging interdisciplinary
collaboration, creating incentives that reward research innovation
and collaboration, and attracting and training new diabetes investigators.
By employing powerful new technologies, researchers are poised
to solve the most vexing problems of type 1 diabetes research.
It is well known, for example, that patients have already lost
most of their beta cells by the time type 1 diabetes is diagnosed.
Having a way to measure the actual number of beta cells would greatly
help researchers in their quest to develop new therapies. State-of-the-art
diagnostic tools, such as magnetic resonance imaging (MRI) and
positron emission tomography (PET), are giving hope that beta cell
mass can be assessed in real time to judge the effects of promising
therapies. Imaging technologies are also being applied to better
understand the brain’s response to hypoglycemia.
Advances and Emerging Opportunities in Type 1 Diabetes Research:
A Strategic Plan was developed under the leadership of the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), the part of the NIH that heads the federal research
effort in diabetes, with oversight from the Diabetes Mellitus
Interagency Coordinating Committee. The document, which resulted
from an extensive planning process that sought the input of patient
advocacy groups and outside scientific experts in type 1 diabetes
research, may be viewed on the NIDDK web site http://www.T1Diabetes.nih.gov/plan.
Single copies are free of charge from NIDDK's National Diabetes
Information Clearinghouse at 1-800-860-8747. For more information
about research in type 1 diabetes, see www.T1Diabetes.nih.gov and www.ClinicalTrials.gov.
NIDDK, part of the National Institutes of Health (NIH), conducts
and supports research on diabetes; endocrine and metabolic diseases;
digestive diseases, nutrition, and obesity; and kidney, urologic
and hematologic diseases. Spanning the full spectrum of medicine
and afflicting people of all ages and ethnic groups, these diseases
encompass some of the most common, severe, and disabling conditions
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.