Research in Mice Suggests Possible New Diabetes Treatment

BOSTON — June, 2001— A study reported in this month's Journal of Clinical Investigation suggests that type 1 diabetes in mice might be stopped and reversed with a two part treatment that re-trains the immune system to stop attacking islet cells, and then encourages remaining islet cells to multiply.

If these results are confirmed by other researchers, this could lead to a potentially novel treatment for patients with newly diagnosed diabetes at or near the time they develop symptoms of the condition.

The two-part treatment involves first triggering the expression of a substance called TNF-alpha in the mice in an attempt to destroy the immune cells that had gone awry and were leading to the destruction of insulin-producing cells in the pancreas.

The second part of the process involves injecting the diabetic mice with donor blood cells. This treatment re-educates the newly emerging immune cells of the mouse, ensuring that they do not attack the islet cells.

This process, described by researchers from Massachusetts General Hospital in Boston, appears to re-train the immune system in order to halt the disease that causes the destruction of islet cells, the insulin-secreting cells of the pancreas. The apparent permanent reversal of established disease allows the host to remake insulin from the pancreas by regrowth of islet cells that are no longer under attack.

"While the results are interesting, it is important to remember that research developed in animal models follows a series of additional steps before we can conclude that it will work in humans," says Diane Mathis, Ph.D., co Section Head of the Joslin's Section on Immunology and Immunogenetics. These steps include replication by other groups of researchers and/or testing of the research in higher animals. If this is achieved with positive results, then such a treatment may be tested in humans.

"Human testing usually occurs first in very small numbers of humans, and then if that is also positive and shows no side-effects, larger scale clinical trials over a period of months and years are embarked upon," she says. This process can take several years before one can conclude whether a treatment actually works in humans.

"As was witnessed in the recent Type 1 prevention study (DPT-1), however, even when this rigorous scientific process occurs, the end result may be that the large-scale clinical trials show that the tested treatment doesn't work in humans, although we always hope that is not the case," she says.

In the DPT-1, for example, research begun in animals in the 1980s, and then done in small numbers of humans at Joslin in Boston in the early 1990s, showed that injecting small amounts of insulin in "pre-diabetics" identified through testing might prevent the disease. These findings, published in prestigious peer review journals, led to a multi-year, multi-center clinical trial testing insulin injections versus no treatment in 339 "pre-diabetics." The results of that study, released this past week, showed that in fact, at the levels given, insulin injections have no effect in preventing diabetes in humans.

A second arm of the study, which is testing whether oral insulin can prevent diabetes through an entirely different mechanism, is still ongoing and still offers hope for a treatment to prevent diabetes. Researchers are still recruiting for this study, and other potential treatments for "pre-diabetes" are being investigated and on the horizon.

"The lesson in all of this research is that it is important for people who have type 1 diabetes in their family to have their immediate relatives screened for pre-diabetes, and to be aware of the symptoms of full-blown diabetes," says Mathis. "By so doing, they can potentially benefit as new potential treatments for preventing diabetes or treating it at diagnosis become available."

For information on how to be tested for pre-diabetes and to determine whether you might qualify for the nationwide oral insulin study to prevent diabetes, family members of someone with type 1 diabetes, please call (617) 732-2524 or 1-800-425-8361.