Little children shall lead us

Each year the percentage of U.S. children diagnosed with type 1 diabetes creeps up, and the average age at which they are diagnosed creeps down. As with so many other autoimmune illnesses, we don’t know what triggers the disease and we don’t know how to prevent it or delay it very long. The history of type 1 prevention trials is not a happy one: Many agents may help some patients to maintain insulin secretion but generally do so only for a few months.

Looking more closely at subgroups within those recently diagnosed with type 1, however, may give us better clues for drug strategies, suggested Carla Greenbaum, director of diabetes research at Benaroya Research Institute in Seattle, in a lecture this month at Joslin Diabetes Center.

If you plot the loss of insulin production over time among these patients and separate the patients by age, you see that “in adults, it’s a completely different pattern,” she said. Children typically are diagnosed with less insulin production and lose it far more quickly than adults.

That pattern argues for some clinical trials that only include children since the benefits of treatment may be easier to spot when the attack is moving so quickly, Greenbaum said. Studying this population may aid in understanding how autoimmune attacks progress in their most active periods, and to clarify whether these periods may include stages of remission and relapse, as found in multiple sclerosis. Moreover, trial groups could be much smaller.

Researchers would, of course, need to maintain exquisite care with this deeply vulnerable population, and to test treatments first in adults to make sure that no harm ensues to children. But we shouldn’t have to show efficacy in adults before we can try to show efficacy in children, she maintained, adding that the FDA hurdle should be efficacy before diagnosis, when the benefits of treatment are potentially far greater.

For decades we’ve had reasonably good tools to identify those at highest risks of type 1, and we can use these tools early on, Greenbaum noted. “To prevent disease, we’ll have to treat it in infancy or the first two years, turning it into a chronic disease like every other autoimmune disease for which we have therapy.”