UCLA study finds clues to diabetes puzzle

A diabetes epidemic that appears to have claimed the life of composer Johann Sebastian Bach may explain baffling disparities in the disease’s rates among 21st-century ethnic groups, a UCLA geographer and evolutionary biologist says in the current issue of Nature.

Aside from speculating that many people may carry genes that predispose them to diabetes, researchers have been at loss to explain why, for instance, only 2 percent of Europeans contract the disease as opposed to 13 percent of African Americans, 17 percent of U.S. Latinos and up to 50 percent of Native Americans.

“Immediately following Europe’s last widespread famines centuries ago, a diabetes epidemic appears to have killed a large number of Europeans with these genes before they could be passed on to successive generations,” said Jared Diamond, a UCLA professor of geography and environmental heath sciences. “Meanwhile, traditionally poor or rural non-European populations have not experienced a diabetes epidemic — until lately. So these people still carry the genes in large measure, and as a result they become highly prone to diabetes when they move into urban or Westernized settings, where the disease’s risk factors are more common.”

If accurate, Diamond’s theory means today’s soaring diabetes rates will continue to mount as people whose ancestors were never exposed to the epidemic adopt the disease’s twin risk factors: abundant food and more sedentary lifestyles. Already, the disease affects 150 million worldwide.

“At its present rate of increase, within a few decades diabetes will become one of the world’s commonest diseases and biggest public health problems with an estimated minimum of half-a-billion cases,” Diamond writes in the June 5 Nature article.

The findings relate only to type II — or so-called adult-onset — diabetes, a form of resistance to insulin, the human hormone responsible for controlling blood sugar. When left unchecked, elevated levels of blood sugar can result in the loss of limbs, vision or life, as well as an increased risk of cardiovascular disease. Adult-onset diabetes often can be controlled through dietary changes and exercise.

Diamond, the Pulitzer Prize–winning author of “Guns, Germs and Steel: The Fates of Human Societies” (W.W. Norton, 1997) and winner of the National Medal of Science, researched current and historic type II diabetes rates among nine different population groups in 24 regions. He then examined the groups’ food history, including improvements in farming, Westernization or urbanization.

He found that diabetes rates have risen in lock step with living standards for the populations now most prone to the disease, including Arizona’s Pima Indians, U.S. Latinos, Pacific Islanders, Westernized Australian Aborigines, African Americans, and urban Asians and eastern Indians. When Yemenite Jews were airlifted to Israel from starving conditions several decades ago, their diabetes rates jumped from 4 percent to 13 percent. When New Guineans moved from a rural to urban setting, their diabetes rate shot from zero to 37 percent, he found.

“Diabetes is a disease of increasing affluence,” he said. “People eat more and risk developing diabetic symptoms when they have more money.”

Diamond’s findings are consistent with a long-standing theory of an evolutionary advantage to insulin resistance, which would tend to favor populations with so-called “thrifty genes” that promote metabolism and storage of blood sugars, thus allowing their carriers to better survive periodic famines.

“Much like the gene that protects against malaria but also predisposes so many people of African ancestry to sickle-cell anemia, the ’thrifty gene’ is a double-edged sword that becomes a liability only after living standards improve,” Diamond said. “Until a stable food source is secured, the gene helps people survive famines, but afterward it puts them at risk for the dangers of diabetes.”

Europe was as prone through the Middle Ages and Renaissance to periodic famines as any place, Diamond points out. European countries just happened to develop stable food sources earlier than other parts of the globe. He contends that a diabetes epidemic swept through Europe following the region’s last famines, beginning in the late 1600s.

“Europe’s new reliability of adequate food supplies eliminated most European diabetes-prone bearers of the thrifty gene,” Diamond said.

Groups with the highest diabetes rates today, meanwhile, were until fairly recently at periodic risk for starvation, so natural selection favored those who retained the “thrifty gene.” These groups often experienced an “extra bout” of natural selection when an especially brutal famine in historic times further concentrated the gene’s carriers in the population, Diamond found.

For instance, Arizona’s Pima Indians experienced crop failures, widespread starvation, and the likely enrichment of the surviving population with thrifty genes after white settlers blocked access in the late 19th century to a traditional source of irrigation water. With 50 percent of the tribe now diagnosed as diabetic, the Pimas today lay claim to the world’s highest diabetes rates.

Diamond’s theory would also explain another disparity in diabetes rates that have puzzled researchers: why white Americans and Australians of European extraction are three to four times more likely than Europeans still living in Europe to be diagnosed with the disease.

“The Europeans who stayed at home tended to be richer that those who emigrated, and the genotype that predisposed the stay-at-homes to diabetes may already have been selected out by centuries of abundant food,” Diamond said. “Those who emigrated may have been the starvation-prone poor such as the Irish who flocked to America during the Potato Famine of the 1840s. These immigrants may carry the thrifty gene in larger proportion because they did not enjoy the abundance in their homeland.”

Bach’s medical history is too poorly documented to pinpoint the cause of his death with any certainty, but what is known of his last years is consistent with an epidemic of type II diabetes that was sweeping Germany at the time, Diamond found.

“The corpulence of his face and hands in the sole authenticated portrait of him, the accounts of deteriorating vision in his later years and the evident deterioration of his handwriting, possibly secondary to his failing vision, are consistent with a diagnosis of type II diabetes,” he said. “The disease certainly occurred in Germany during Bach’s lifetime, being known as ’honigsusse Harnruhr’ or honey-sweet urine disease.”