At Work With the Pima
By Andrew Curry May 2008 Research and News---Researchers,
Researchers from the National Institutes of Health first visited Arizona's Pima Indians in the 1960s. They were looking for clues to the causes of rheumatoid arthritis, and hoping that the Pima's close-knit society would provide a good sample population.
As they began conducting medical exams on the tribe, they quickly forgot about arthritis. It turned out that an incredibly large number of Pima had diabetes. More than 40 years later, the problem has gotten even worse. Today, diabetes rates among the Phoenix-area tribe are almost seven times the national average. "They have the highest prevalence of diabetes in the world," says Clifton Bogardus III, MD, a researcher at the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "Two thirds of adults over 40 have diabetes."
Since 1965, NIH researchers have been trying to find out why. Over time, NIDDK has forged a close relationship with the Gila River Indian Community, the largest group of Pima in the Southwest. With the help of this unique population, they began a long-term longitudinal study of thousands of Pima. Doctors and epidemiologists examine and interview everyone at Gila River over the age of 5 every two years to create a complete medical history. The study is now in its fifth decade, providing researchers with a massive database of information on how diabetes affects people over time and across generations.
Clifton Bogardus III, MD
Clinical Researcher,
ADA Distinguished Clinical Scientist Grant
From the very beginning, the results of the NIDDK's work in Arizona have changed the way doctors look at diabetes. Research among the Pima helped establish the now commonly accepted diagnostic definition of diabetes, for instance. The NIDDK's work with the Pima also helped narrow down some of the most important risk factors for diabetes, including insulin resistance, being overweight, and lower rates of insulin release into the bloodstream. It turns out that these risk factors are often inherited, part of a person's DNA in the same way as straight hair or brown eyes.
As part of the project's latest phase, Bogardus and a team of scientists at NIDDK are searching for the genetic roots of diabetes. A former Army doctor, Bogardus has been working with the tribe since 1982, when he moved from Vermont to Phoenix to take a position at the NIDDK branch there. With the help of funding from the ADA, Bogardus now hopes to figure out what part of the Pima's genes are responsible for these risk factors.
Since the Pima are such a small population and share so many of the same genetic characteristics—and have such an unusually high rate of diabetes— they are an ideal group for researchers looking for these causes of the disease. "They're a more genetically homogenous group than a bunch of Caucasians," Bogardus says. "Hopefully we'll be able to see if there's a gene that causes diabetes in the Pima and if it exists in other populations."
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Bogardus is looking for tiny differences, or polymorphisms, in the genes of Pima with diabetes and without. In the past few years, he and his team have sequenced the DNA of 1,700 people, identifying over a million variations. By comparing them with each other, he hopes to single out the genetic differences responsible for making the Pima so much more likely to develop diabetes. "Soon we're hoping to have on our hands which polymorphisms diabetics have in common," he says.
Bogardus isn't the only person looking for a diabetes gene, of course. Other researchers have studied a broad spectrum of Caucasians. One group has looked in particular at the Amish, another tightly knit population. But none of those studies have turned up genes that explain why the Pima get diabetes in such numbers. "We've gone through a very large number of genes associated with diabetes in other populations," Bogardus says. "They never seem to be predictive in the Pima."
If Bogardus can pin down what makes the Pima different, he says it will help target intervention programs designed to stave off the onset of diabetes indefinitely—for the Pima for sure, and perhaps for others as well. Imagine knowing you were at higher risk for developing type 2 diabetes long before it occurred. You'd be able to take steps to tackle your specific risk factors, and doctors would be able to design treatments for those most in need. "With a great deal of effort, they can greatly reduce the risk of getting diabetes," says Bogardus.
Bogardus is excited about what his new research may turn up. But he admits that there's pressure from the people with the most at stake: the Pima. "On average, they're happy to have us trying to figure out their problems, but there's a frustration that we haven't figured it out yet," Bogardus says. "I always get questions about what's taking so long."
Andrew Curry is a freelance writer and former general editor of Smithsonian magazine.