It was a strong sign of a genetic effect, without revealing the active genes themselves, a much harder question. Molecular investigations of diabetes genes have bogged down not only at NIDDK but also at laboratories around the world. As Finnish geneticist Leena Peltonen wrote in a recent review, “The enthusiasm regarding the use of population isolates for the identification of predisposing genes for common, polygenic diseases has turned to a silent drudgery.” Translation: Isolated, inbred groups like the Finns, the Amish, and the Pimas were a happy hunting ground for medical geneticists a decade ago, thanks to successes in probing such groups for rare disease genes. But type 2 diabetes, Parkinson’s, heart disease, Alzheimer’s—the common maladies of mankind—give up their genes reluctantly. The gene variants involved must be numerous, cryptic, and weak.
If the diabetes genes can’t be found, can’t they at least be stopped?
The Zuni Pueblo—“pueblo” refers to the contiguous adobe houses the Indians used to build—lies on the high desert of New Mexico, just over the Arizona line. Unlike Gila River, the Zuni reservation has neither mountain ranges nor cities around it. Its landmark is a startling red mesa jutting straight up from the plain. It is called Dowa Yallane. The Zuni hid on Dowa Yallane for a time in the late 1600s, after revolting against the Spaniards and killing a missionary priest.
Like other tribes, the Zuni were decimated by epidemics and warfare brought to them by European Americans. The natives passed through a second population bottleneck, losing 90 percent of their numbers, then rebounded during the 20th century. The fragmentation of the Indian nations, followed by intermarrying and population expansion, was not the best means of maintaining genetic health. The Zuni, a community of 10,000, have the highest measured rate of cystic fibrosis in the world, as well as the highest rate of end-stage kidney disease. Two sharply different sorts of disease genes are at work. The gene variant for cystic fibrosis was introduced by a Spanish or Italian “founder” many generations ago, according to the marker analysis. The gene took off within the pueblo, and one in 13 residents carry it today, but the disease doesn’t strike unless two copies are passed to a child from two parental carriers.
Cystic fibrosis needs no environmental trigger. The kidney disease that afflicts Zuni, however, is related to lifestyle because type 2 diabetes is the cause of the majority of the cases. About one-third of Zuni adults over 40 have diabetes. People also suffer from a nondiabetic form of kidney disease. Some even exhibit both types at once. It is disturbing to enter the tribe’s newly renovated dialysis clinic, which treats three shifts of patients each day, and see the young bodies as well as the elderly hooked up to the machines and their pale, drawn faces while their blood is cleansed.
Last fall a team of researchers from the University of New Mexico, having tracked kidney disease on the reservation for several years, persuaded the tribal council to approve a DNA analysis. The scan of affected families may identify relevant genetic susceptibilities, but the geneticist for the project cautioned the council that the results will be slow to come. When I met with the Zuni leaders afterward, they told me they were not holding their breath.
“We asked them, ‘You’ve already taken blood. Now what?’ ” recalled Carmelita Sanchez, the lieutenant governor.
“What’s the intervention at the time the research is going on?” Carleton Albert, a councilman, said.
“Interim solutions, that’s what we’re asking for,” said another councilman, Edward Wemytewa. “Add a human dimension to the science. When you do your survey of people, do a lecture on behavior modification at the same time. Maybe a talk about the value of our traditional foods.”
“We need to have regular updates, and we need to be informed when you make a presentation,” Albert said.
The project leader, Philip Zager, a kidney specialist at the University of New Mexico, assured me that the genetics phase of the Zuni Kidney Project was going to be “community based.” Albert’s retort to that was, “They say they want to listen, but I’m not sure they do.”
Diabetes and kidney disease are so severe that the Zuni could not spurn the genetic approach. The hopes of most members of the council were pinned elsewhere, however. In the late 1990s medical researchers at NIDDK and in Finland conducted trials combining exercise, diet, and drug therapy as a way to head off diabetes in overweight people with high blood sugar. The American study, called the Diabetes Prevention Program, included Zuni and Pima volunteers among its 3,200 participants. In both trials the aggressive interventions did not prevent diabetes in everyone who was followed, but the onset of the disease was slowed overall.
Between 1991 and 2000 the number of adults with type 2 diabetes in the United States increased by 49 percent. Diabetes prevalence rates among adults: 50 percent of Pimas, 11 percent of African Americans, 8 percent of Hispanics, and 8 percent of Caucasians.
How exercise helps is murky, but increased activity seems to stimulate a gene called GLUT4. The gene’s protein aids insulin in transporting glucose into muscle cells. Meanwhile, losing weight cuts back the hormonal activity of fat cells, which in turn reduces a person’s resistance to insulin. When the results of the trials were published three years ago, Indian Health Service doctors and tribal health officials got the message: Environment was the way to go.
Ruby Wolf is the unofficial wellness czar of the Zuni. Thanks to federal grants, Wolf’s Healthy Lifestyles campaign is an inescapable fixture of the community. T-shirts and posters proclaiming the slogan are ubiquitous. Once a month the Healthy Lifestyles staff holds a rally, race, or some other event to promote weight loss, better nutrition, and fitness. “We know what works,” said Wolf, “but it’s got to be fun and educational.” A new swimming pool, spinning (stationary bicycle) classes, school lectures, public weigh-ins, softball tournaments —I couldn’t write down fast enough all the things she had planned for the Zuni.
“We don’t have a minute to lose,” she said, adding that her parents died of diabetes. “That’s where our ambition and drive come from. I want nonstop stimulus and nonstop intervention.
“People say about diabetes, ‘Well, I guess it’s my destiny.’ No. I went to our spiritual leaders and asked them about our prayer that says, ‘From this day forward the road and path are what we choose.’ And they said, ‘Yes, that is a powerful prayer.’ I took it for the sweatshirt we’re giving away this Saturday. If you run, if you’re 4 years old or 89, you get one.”
Wolf showed me the handsome hooded sweatshirt, with its circular emblem on the back and the words “Zuni Healthy Lifestyles, Your Life’s Direction.” “If we’re going to prevent diabetes, we’ve got to build on the 25 percent of the community that comes to our events,” she said.
She has even hired an epidemiologist to gather health data on the participants because doubters demanded scientific evidence of the gains. The epidemiologist, Chetna Mehrotra, is an Indian, but an Asian Indian; she was as enthusiastic about conquering diabetes as Wolf. I couldn’t resist pointing out the closeness in DNA between the two women. The incidence of type 2 diabetes, for that matter, is increasing faster in Asia than anywhere outside the Native American communities. But Wolf and Mehrotra were not interested in genes.
Piñon smoke and red dust hung in the wintry air of Zuni Pueblo. Responding to the health campaign, the community store has put a salad bar next to the hamburger grill and soda cooler, and I saw people using it. Leaving town at dusk, I drove onto a dirt road toward the snow-patched flanks of the sacred mesa, Dowa Yallane. At a bend in the road, I saw a lone warrior in black, jogging.