| Oral Insulin Does Not Prevent
Type 1 Diabetes
Insulin taken orally does not delay or prevent type 1
diabetes in people at moderate risk (25 to 50 percent
likelihood) of developing type 1 diabetes in 5 years,
researchers reported today at the annual meeting of the
American Diabetes Association. The finding emerged from
the second trial conducted as part of the Diabetes
Prevention Trial-Type 1 (DPT-1), which ended last month.
The other DPT-1 trial, completed two years ago, found
that low-dose insulin injections failed to prevent or
delay type 1 diabetes in people at high risk (50 percent
or greater chance) of developing the disease in 5 years.
A total of 372 people took part in the trial
comparing the rate of progression to type 1 diabetes
among those randomized to take a daily capsule of
insulin crystals (7.5 mg.) or a placebo consisting of a
harmless, inactive substance. All participants had a 25
to 50 percent chance of developing type 1 diabetes in
the next 5 years, a calculation based on genetic,
immunologic, and metabolic tests done before enrollment.
Upon joining the trial, which began in 1996, all
subjects were making normal amounts of their own
insulin. Their ages ranged from 3 to 45 years old, with
a median age of 10 years.
After an average of 4.3 years of observation, about
35 percent of people developed type 1 diabetes in each
group. The annual rate of onset (7.2 percent per year)
was nearly the same in both groups. Testing done as part
of the study detected most cases of diabetes before
symptoms developed, enabling patients to get prompt,
early treatment. No side effects were linked to oral
insulin.
“This result is very disappointing, but it’s
important to remember that negative findings also
provide important scientific answers,” said study chair
Dr. Jay Skyler of the University of Miami. “We’ve
learned a great deal from both DPT-1 trials about the
natural history of type 1 diabetes and the immune events
that underlie it, and that knowledge is crucial to
future prevention efforts.” Although oral insulin did
not prevent or delay diabetes, the study confirmed and
expanded on the observations made in the low-dose
insulin injection trial that the risk of developing
diabetes can be predicted by subjects’ characteristics
and laboratory tests performed during screening.
The oral insulin study was based on the hypothesis
that insulin taken orally might suppress the immune
system’s destructive attack on beta cells. Studies in
the non-obese diabetic (NOD) mouse, an animal model of
type 1 diabetes, had shown that oral insulin given
before diabetes development could reduce or delay onset
of the disease. By “feeding” a person insulin, the
immune cells in the digestive tract might learn to
recognize insulin in a different way and favor the
development of immune responses that delay the onset or
progression of diabetes or prevent its occurrence
altogether.
The oral insulin trial is the third large study that
failed to prevent type 1 diabetes in at-risk people. The
European Nicotinamide Diabetes Intervention Trial
(ENDIT) also failed to prevent or delay type 1 diabetes
with nicotinamide, a vitamin present in small amounts in
a normal diet.
“The findings of these trials underscore how much we
still have to learn about the underlying immune events
that lead to type 1 diabetes,” said Dr. Judith Fradkin,
director of the Division of Diabetes, Endocrinology, and
Metabolic Diseases in the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK). “We plan to
closely follow people at risk to try to understand the
disease better and to find ways to stop the complex
autoimmune process that leads to type 1 diabetes. We
will also be testing approaches to preserve the ability
to make insulin in people with newly diagnosed type 1
diabetes.”
Upcoming clinical trials will be conducted under Type
1 Diabetes TrialNet, a collaborative network of clinical
centers dedicated to preventing type 1 diabetes and
preserving insulin production in new-onset patients. The
first trials are scheduled to begin enrolling patients
in the fall of 2003.
About 17 million people in the United States have
diabetes, the most common cause of blindness, kidney
failure, and amputations in adults and a major cause of
heart disease and stroke. About 1 million have type 1
diabetes. Formerly known as juvenile onset or
insulin-dependent diabetes, type 1 diabetes usually
begins in children and adults under age 30. It develops
when the body’s immune system attacks the
insulin-producing cells of the pancreas.
The DPT-1 trials were funded by the NIDDK, the
National Institute of Allergy and Infectious Diseases,
the National Institute of Child Health and Human
Development, and the National Center for Research
Resources, all parts of the National Institutes of
Health under the Department of Health and Human
Services, as well as the American Diabetes Association
and the Juvenile Diabetes Research Foundation
International. |
