|Studies Aim to Preserve Insulin Production in Type 1 Diabetes
Type 1 Diabetes TrialNet Centers Begin New Trials
Eighteen medical centers in the United States, Canada, Europe, and Australia
have begun new clinical studies in type 1 diabetes, the National Institutes of
Health (NIH) announced today at the annual scientific meeting of the American
Diabetes Association (ADA). The NIH-funded studies seek to slow or stop the immune
system’s attack on insulin-producing cells in two groups of people: those newly
diagnosed with type 1 diabetes and those at risk for developing it.
“It would be a tremendous step forward if insulin-producing cells can be shielded
from further destruction by immune cells,” said Elias A. Zerhouni, M.D., NIH
Director. “We stand to learn a great deal from these promising studies, which
are exploiting the knowledge gained from earlier research in immunology, endocrinology,
and the biology of type 1 diabetes.”
Type 1 diabetes is an autoimmune disease that accounts for 5 to 10 percent of
diagnosed diabetes cases in the United States — up to a million people. It arises
when a person’s own immune system destroys beta cells in the pancreas. Beta cells
sense blood glucose and produce the hormone insulin, which regulates glucose
and converts it to energy. Formerly called juvenile onset diabetes, type 1 diabetes
usually develops in children and young adults. People with this form of diabetes
typically need three or more insulin injections a day or treatment with an insulin
pump, as well as careful monitoring of blood glucose and attention to diet and
exercise, to properly control their blood glucose.
The immune destruction of beta cells begins well before a person develops the
symptoms of diabetes and continues long after the disease is diagnosed. During
the “honeymoon phase,” the months after diabetes is diagnosed, most patients
still have a reservoir of functioning beta cells that, with the help of insulin
injections, makes it easier to control blood glucose. If the honeymoon period
can be extended, researchers hope that more patients would be able to tightly
control their blood glucose. Well controlled glucose is critical to preventing
or delaying serious damage to the eyes, nerves, kidneys, heart, and blood vessels.
Studies for Newly Diagnosed Patients
Researchers participating in Type 1 Diabetes TrialNet are now conducting two
studies that seek to safely preserve insulin production in people diagnosed
with type 1 diabetes in the previous 3 months. “The more beta cells a person
has, the easier it is to control diabetes and prevent complications,” said
TrialNet chair Jay Skyler, M.D., of the University of Miami. “With these studies,
we hope to stop the immune system’s attack on these cells and keep the disease
from getting worse.”
A number of studies have already shed light on how a subgroup of T cells, the “warrior” cells
of the immune system, seek out and attack insulin-producing cells. B cells, another
group of immune cells that were initially seen as idle bystanders, are now thought
to raise the alarm by presenting antigens to T cells, urging them to take action.
This new insight is now being tested in a clinical study that seeks to “turn
off” the alert by reducing the number of circulating B cells. In this study,
researchers are testing the use of Rituximab, a monoclonal antibody that binds
to a receptor on the surface of B cells and destroys them. Rituximab, approved
by the Food and Drug Administration to treat B cell non-Hodgkin’s lymphomas,
has also been used with minimal toxicity to treat autoimmune diseases, such as
chronic idiopathic thrombocytopenia, myasthenia gravis, and rheumatoid arthritis.
In another TrialNet study, patients are randomly assigned to one of three groups
receiving mycophenolate mofetil (MMF) alone; MMF plus daclizumab (DZB); or placebo.
Both MMF and DZB, which slow immune cell activity, have been approved by the
Food and Drug Administration to prevent organ rejection after an organ transplant.
Both the new Rituximab trial and the ongoing MMF/DZB trial are recruiting patients
with type 1 diabetes diagnosed within the previous three months. In each study,
patients are randomly assigned to receive the experimental treatment or placebo.
Participants will be closely monitored for any possible side effects of the drugs.
Study for Newborns at Risk for Type 1 Diabetes
Some studies show that the immune destruction of beta cells is linked to an inflammatory
process triggered by specific cytokines, molecules that regulate communication
among immune cells. TrialNet researchers hope to quell this inflammation and
prevent the development of autoantibodies with docosahexaenoic acid (DHA),
an omega-3 fatty acid that may have anti-inflammatory benefits. Nutritional
Intervention to Prevent Type 1 Diabetes (NIP) is a pilot study of DHA being
conducted in babies less than 5 months old who have immediate family members
with type 1 diabetes. The NIP study is also screening pregnant mothers in their
third trimester whose babies are at risk for type 1 diabetes, either because
the mother has type 1 diabetes herself or other immediate relatives have the
Natural History Study
TrialNet researchers are also probing the causes of type 1 diabetes by examining
the immune and metabolic events that precede the onset of diabetes symptoms.
They are screening two groups of relatives of those with type 1 diabetes: first-degree
relatives ages 1 to 45 and second-degree relatives ages 1 to 20. Screening
involves a simple blood test for the autoantibodies that appear in at-risk
people years before diabetes develops. The presence of autoantibodies to GAD,
IA-2, and insulin point to a greater risk for developing type 1 diabetes. For
a person with high-risk genes who has all three antibodies, the risk of developing
diabetes in the next 5 years is greater than 50 percent.
After enrolling in the study, participants will be closely monitored for diabetes
development and may be eligible to participate in studies that try to arrest
Type 1 diabetes is caused by a combination of genetic and environmental factors.
About 18 regions of the genome have been linked to type 1 diabetes risk. The
most well studied region is IDDM1, which contains the human leukocyte antigen
(HLA) genes that encode immune response proteins. Specific variations in these
genes predispose a person to the disease, but having them does not guarantee
that someone will develop the disease. One or more external co-factors, such
as a viral infection or component of the diet, appear to trigger immune cells’ misguided
attack on beta cells in genetically susceptible people. Researchers are working
to identify all the genes and environmental triggers that contribute to the risk
of developing type 1 diabetes, and they have already learned a great deal about
assessing an individual’s level of risk.
The studies are funded by the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development,
and the National Institute of Allergy and Infectious Diseases within the NIH.
The ADA and the Juvenile Diabetes Research Foundation International (JDRF) also
support the initiative.
For more information about the studies, see www.DiabetesTrialnet.org or call
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.