Local diabetes researchers seek to unlock mysteries of vitamin D

Finnish babies born in the 1960s and raised on mega-doses of vitamin D had dramatically lower risk of developing type 1 diabetes, a serious autoimmune disease that requires lifelong injections of insulin.

Was it a case of cause and effect? Seattle researchers are trying to find out.

Despite suggestions from several studies in the past decade that vitamin D may offer strong protection against juvenile diabetes, none has shown conclusively that there's more than a chance association.

But researchers at the Pacific Northwest Diabetes Research Institute (PDRI) are working to unearth definitive proof of vitamin D's powers.

PDRI scientists are among a group of researchers scattered in four countries who are tracking children at high risk for type 1 diabetes for 15 years to identify the environmental triggers of the disease.

At the same time, Dr. Bill Hagopian, a principal scientist at PDRI, has joined Canadian researchers to conduct a randomized controlled trial to test directly whether vitamin D supplements — and at what levels — might prevent the disease.

Their quest got renewed impetus last month when British researchers published a collective analysis of five previous studies from around the world and calculated that taking vitamin D reduced the risk of developing type 1 diabetes by almost a third. Children who started supplements early in infancy and who took the highest doses — 2,000 International Units (IU), or 10 times the current U.S. daily recommendation for infants — reaped the greatest benefit.

"Vitamin D is one of the most promising" of the environmental factors, Hagopian said. "This may be the tip of the iceberg in terms of potential benefits of vitamin D on autoimmune diseases."

Type 1

Type 1 diabetes springs from a mysterious interaction between genetics and environment. As many as 90 percent of people with type 1 diabetes are born with a diabetes-enabling version of a set of genes called human leukocyte antigens. Yet only about one out of 30 people with this genetic susceptibility ever develop type 1 diabetes. In addition, the vast majority of children who get it do not have parents or siblings with the disease.

Researchers suspect that's because half of the risk for type 1 diabetes lies in the environment. They have a lengthy list of suspected culprits: gluten in wheat, oats or barley; cow's milk; allergies; gut bacteria; stress; antioxidant deficiency and the polio-related Coxsackie virus all have been tied to heightened odds of type 1 diabetes.

Epidemiologic studies, however, have produced contradictory or conflicting findings; no single environmental trigger has yet been implicated with absolute certainty.

About 15,000 U.S. children and adolescents are diagnosed with type 1 diabetes each year. Unlike with the more common type 2 diabetes, obesity and lack of exercise play no role in type 1 diabetes. Rather, the person's immune system turns against the body, destroying cells that produce insulin, a hormone needed to help convert food into energy.

Vitamin D is thought to help suppress the immune response responsible for the attack on the insulin-making cells. But no one understands exactly how that happens, leading to lingering scientific skepticism about vitamin D's promise, said Christiane Hampe, a diabetes researcher at the University of Washington.

What researchers do know is that vitamin D absorption — both from sun's rays and supplements — has fallen in recent decades. For instance, Finland, whose northern region gets just two hours of sun a day in December, has one of the world's highest reported rates of type 1 diabetes. Since 1964, the daily recommended dose for Finnish infants has been lowered three times, from at least 4,000 IU to one-tenth of that today, reflecting medicine's shift toward the minimum doses necessary.

It is possible to go overboard with vitamin D supplements and trigger dangerous calcium deposits in the kidneys and blood vessels, but experts say it takes a lot: more than 10,000 IU a day for a year.

7,800 to be tracked

A 2001 review of 31 years of medical records for more than 10,000 Finnish babies born during 1966 found that infants who took less than the then-maximum suggested dose of 2,000 IU of vitamin D daily later developed type 1 diabetes five times more often than those who took the full dose.

Hagopian and his international colleagues are testing that tie more rigorously. Scientists in Seattle, Colorado, Florida, Germany, Sweden and Finland plan to track 7,800 infants into their teen years to build the most statistically powerful database yet of their diet and environmental exposures. Every three months, researchers take blood and stool samples to measure actual levels of vitamin D, toxins and other agents.

Enrollment in the study is nearly two-thirds complete. Researchers hope to sign up 500 additional high-risk babies in Seattle, particularly those with immediate family members with type 1 diabetes.

But Hagopian is optimistic enough to simultaneously prepare to put the vitamin D hypothesis to the ultimate test: isolating vitamin D's effect by randomly splitting a group and giving supplements to only half of the participants. A steering committee within the U.S. National Institutes of Health may vote as early as this week on whether to fund the trial.

Dr. Shayne Taback, an associate professor at the University of Manitoba who is leading the randomized controlled trial, said he hopes to prove not only whether vitamin D prevents type 1 diabetes, but at what dose.

Taback suspects the current recommended levels are too low to ward off the disease.

"If that's the case, vitamin D supplementation would indeed make a significant dent in new cases of type 1 diabetes in many parts of the world," he said.

Kyung Song: 206-464-2423 or ksong@seattletimes.com