Cornell Medical College Advances
Immune Deficiency Causing Type 1 Diabetes
By HERMAN ROSEN, M.D.
article recently published in the Journal of Clinical Investigation
by lead authors Drs. Noel Maclaren and Anjli Kukreja of the
Department of Pediatrics at Weill Cornell Medical College investigates
60 patients with immune-mediated type 1 diabetes. The study addresses
what predisposes to this condition, and the latest measures for
diagnosis and therapy. The authors suggest a new strategy for
combating the disease: stimulate rather than suppress the patientís
In immune-mediated diabetes, a genetic predisposition to autoimmunity
destroys the pancreatic beta cells that secrete insulin. Type
1 diabetes can also occur, less commonly, without autoimmunity.
Insulin therapy is always required in type 1 diabetes, which accounts
for about 10 percent of all diabetics.
In all their subjects, the authors found a deficiency in certain
kinds of white blood cells, called T regulatory cells, because
they regulate the immune system and protect the body from being
attacked by its own defenses.
The deficiency is an absolute requirement for immune-mediated
diabetes, but not everyone with the deficiency will develop the
condition, but may develop other autoimmune diseases, such as
thyroiditis, Addisonís disease, vitiligo or multiple sclerosis.
Testing for this defect in T regulatory cells is useful in diagnosing
the immune form of type 1 diabetes, and predicting whether a relative
might develop it. First, the family member is tested for antibodies
to their own islet cells. If the test is positive it indicates
that the person is progressing toward diabetes, but not necessarily
clinical disease. Then the family member is tested for T regulatory
cells. Finding a deficiency at this time is strongly predictive
that type 1 diabetes will occur.
For years, physicians have tried to treat this autoimmune disease
by suppressing the immune system, and results have been disappointing.
The need for insulin persists and suppression of the immune system
predisposes to various infectious and malignant diseases. However,
results of this study suggest a new therapeutic strategy: instead
of suppressing the immune system, stimulate a select part of it,
the T regulatory cells.
To accomplish this stimulation of T regulatory cells, the authors
point to a substance, alpha-galactosylceramide, found in sea sponges
near Japan, which has turned out to be such an immunostimulant.
Reports of its trials in non-obese diabetic mice have been encouraging
say the authors. They suggest human trials of synthetic forms
of the stimulant soon.#
Dr. Herman Rosen is Clinical Professor of Medicine at Weill
Cornell Medical College.
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