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Ultrasound at 18 weeks (Globe files/Globe files)
Ultrasound at 18 weeks (Globe files/Globe files)

Part two of two

A new prime suspect behind the global upsurge in obesity and diabetes: the womb Add to ...

In the 1980s, back when obesity and diabetes were considered problems, not plagues, a British researcher dished up a wild idea to explain the diet-related ills of the world.

While studying the causes of death for England and Wales, David Barker, an epidemiologist with the University of Southampton, stumbled upon the fact that, in the 1970s, deaths due to heart disease were highest in poor regions that 60 years earlier also had the highest rates of infant mortality.

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Prof. Barker considered that curious, since coronary disease was thought to be the result of rich living. He went on to trace the fate of 15,000 people born before 1930 in the English county of Hertfordshire and discovered that those with the lowest birth weights, presumably because their mothers were malnourished, again had the greatest risk of heart disease.

Prof. Barker, who published his initial findings in The Lancet in 1986, eventually came to the conclusion that a mother's nutrition can shape the metabolic future of her baby - affecting the child's lifelong risks for heart disease and all the health problems related to it.

At the time, the idea seemed almost absurd. The prevailing view held that susceptibility to disease was something chiselled into your genes from prehistoric times, not dictated by a pregnant woman's diet. The theory of the thrifty gene ruled the day, with the idea that former hunter-gatherer populations faced steady pressures of feast and famine that gave them fat-storing genes to survive the lean times - thrifty genes that made their descendants, aboriginal people in particular, obese and diabetic in the modern world.

But 25 years on, science, and society, have evolved.

With failed efforts to find a thrifty gene, or any genetic explanation for the rapid global rise in obesity and diabetes, Prof. Barker's hypothesis, better known today as the developmental origins theory, has emerged as a leading explanation. It's also a more attractive one: If correct, it suggests that something can be done to turn the tide.

Rewriting nature's script

Support for the developmental origins idea has grown alongside epigenetics, a budding branch of biology that is forcing a radical rethinking of genetic science as it reveals how the environment can alter DNA.

Dramatic experiments have shown that even small environmental changes can have a powerful, and permanent, impact on the way genes work: Tweaking the diets of pregnant rats, pigs, guinea pigs, rabbits and sheep can induce obesity and a range of other metabolic ills among the offspring. In one case, it changed the colour of a mouse.

The implication is that DNA may be the script that nature provides, but nurturing determines how that script will be performed - and, according to the origins theory, rehearsals begin in the womb.

"It's almost a sensing system of what's going on in the environment, so that a fetus can adapt," says Rosanna Weksberg, an epigenetics researcher at Toronto's Hospital for Sick Children. Problems can arise when the world outside the womb is dramatically different - "there's an epigenetic memory of nutrition."

Growing in a woman who is malnourished - either from eating too little or receiving too few nutrients - primes the fetal DNA to hoard every calorie available, only to be vulnerable to obesity and diabetes in a postnatal world of caloric overload. At the end of the Second World War, for instance, children born to women pregnant during the Dutch "hunger winter" proved susceptible to diabetes, obesity, heart disease and other health problems.

The theory is "such a powerful explanation for what's happening," says Daniel Benyshek, a bio-anthropologist at the University of Nevada, Las Vegas.

"Look at India, where diabetes is growing faster than anywhere else in the world."

Many Indian women grew up hungry in poor villages, he says, only to move up and into urban centres, where they suddenly find themselves - and their children - battling diabetes, an epidemic threatening to undermine all the gains of the country's newly minted middle class.

Indeed, the International Federation of Diabetes predicts that in two decades the number of diabetics worldwide will jump by more than half, to 438 million from 285 million, with three-quarters of those affected in low- and middle-income countries.

In many ways, Prof. Benyshek says, North America's native populations, hammered by diabetes for 50 years, "have been like canaries in a coal mine." They had "decades of really severe economic conditions and deprivation in the first part of the 20th century."

In the mid-1980s, as Prof. Barker worked on his theory, Heather Dean, a pediatric endocrinologist at the Children's Hospital in Winnipeg, began to see aboriginal children with type 2 diabetes. "Oh, oh," she thought. "What is this?"

Children, it was believed, almost always develop type 1 diabetes, where the pancreas simply stops making the insulin needed to turn blood sugar into the fuel that powers the body. Type 2 diabetes was supposed to be an adult's disease - the result of insulin resistance, or a pancreas unable to keep up with the insulin demands of an older, and often, larger body.

Those first children were obese, Dr. Dean says, but obese children in the past always managed,

with their young pancreases, to produce enough insulin. "It shouldn't happen that a 12- or 13-year-old has type 2 diabetes and can't overcome it."

Yet the caseload multiplied - shooting up from a handful a year to more than 70 last year (equal to the number of new patients at her clinic with type 1 diabetes). Meanwhile, a lack of healthy food and exercise cannot fully explain it, she says - not all the children are obese, and a few are as young as 6.

"Something is really affecting, and very quickly accelerating, a child's inability to withstand the factors that lead to disease … ," says Dr. Dean, an assistant dean of medicine at the University of Manitoba. "You have to ask, 'Why is this happening?'"

As she and her colleagues investigated further, they discovered that a child born to a woman with type 2 diabetes before becoming pregnant had a dramatically higher risk of developing the disease in childhood - more than 14 times higher.

They are also finding that nearly every new patient has a mother, grandmother and great-grandmother who also had type 2 diabetes, and each successive generation developed the disease at a younger age.

"It's happened so quickly, it has to suggest an epigenetic phenomenon," she says. Without environmental influences, "genes don't change that quickly."

Skeptics cling to their genes

Not everyone finds the origins theory as compelling. Jeffrey Friedman, a leading obesity researcher at Rockefeller University in New York, feels that it "may be relevant in parts of India and China," but is not powerful enough to explain the story everywhere. Dr. Friedman, who has for years been searching for thrifty genes to explain the sudden rise of obesity on the Pacific island of Kosrae, believes that "evolutionary forces" have the more significant impact on the genes that mould a person's predisposition to be fat or thin.

Jared Diamond, the well-known author and geography professor at the University of California in Los Angeles, also doubts that prenatal conditions, more than DNA, predict future disease risk. In a 2003 paper, he cited studies showing that when one identical twin develops diabetes, the chances are nearly 100 per cent that the disease will strike the other twin too. But the odds are only 20 per cent for fraternal twins, who share the same womb, but different DNA, "suggesting that factors in the uterus play a ... minor role," he wrote.

Prof. Benyshek, however, says that, while there may be susceptibility genes for diabetes, the seeds of today's epidemic among aboriginal people were sown just a few generations ago. In the 1990s, he was part of an unsuccessful attempt to find a "thrifty gene" in the native people of Arizona, particularly the Pima Indians, who have the world's highest diabetes rate.

But it nagged at him that the classic thrifty-gene theory, which he now calls "a relic," applied to former hunters when the Pima had been successful farmers of beans, squash and cotton. Only after ranchers diverted the river that watered their crops, followed by a drought and the start of their sedentary life on a reservation, did famine persist.

By the early 1900s, Prof. Benyshek says, they were dying of scurvy and starvation. So, when he first read about the origins theory in the early 1990s, he suddenly saw the Pima story "as the perfect storm." Babies born to the malnourished Pima women of the 1920s and 1930s were already on the road to developing diabetes, he believes, and passing on that higher risk to the next generations.

"We're arguing now that diabetes is a political, economic disease," he says, "due directly to the deprivation they suffered."

Dogrib dodge the bullet

If the origins theory reveals why the Pima have so much diabetes, Emöke Szathmáry, former president of the University of Manitoba and a biological anthropologist, suspects that it also helps to explain why the Dogrib people of the Northwest Territories have so little.

The Dogrib were once nomadic hunters who lived off caribou and fish, but fur trapping for Europeans allowed them to add flour, baking powder, sugar and tea to their diet as early as the 19th century. Yet even in 1979, Dr. Szathmáry found no cases of diabetes among them, and the prevalence of the disease, according to one recent study, remains low even today.

She suspects that they are in part protected by history: Gold mining and the war delayed their settlement into permanent communities until after the 1950s.

"About 75 per cent of my sample had spent their childhoods on the land, in the sub-Arctic," she says. "They were physically active" - and born to women who lived the same way.

"The trajectory was laid down in utero."

Carolyn Abraham is The Globe and Mail's medical reporter.

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