SCIENCE / Diabetes: a global epidemic: The number of diabetics is rising dramatically. Polynesians and North American Indians are particularly affected. Is it genetic, asks Steve Connor, or the result of poor diet?


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The Independent Culture

FIFTY years ago, the natives of Nauru, a remote atoll in the Pacific, were by and large healthy, athletic and slim. Today, a typical Nauruan is grossly overweight and diabetic. The dramatic reversal in the fortunes of Nauruan health is matched only by the sudden increase in the islanders' wealth; phosphate mines have in the past few decades made them very rich. But why has such material wealth - so often associated with an improvement in health - resulted in such high levels of diabetes and obesity?

The simple answer could be that the islanders have grown fat on a Western diet and no longer practise the active, hunter-gatherer lifestyle of their ancestors. An imported supermarket diet has resulted in a 'coca-colonisation' of the island, where people eat far too many calories and do far too little exercise.

The truth, however, is slightly more complicated than this. Diabetes and its associated obesity has struck many other native populations from Asia to North America since the end of the Second World War. Scientists have reported dramatic increases in diabetes among Polynesians, American Indians, Chinese and some Asian Indians. In China and India alone, scientists believe there will be 50 million diabetics by the year 2000.

Attempts to explain the reasons behind this global epidemic have generated two competing ideas. One proposes that certain racial groups are genetically predisposed to diabetes and obesity because they possess what geneticists term a 'thrifty genotype'. This means that their genes have been selected in a harsh nutritional environment to store food efficiently as fat. The other hypothesis suggests that the diabetic natives from Asia to North America are showing the physical signs of a cultural transition in their diet. The essence of this idea is that today's middle-aged diabetics were foetuses at the time of nutritional austerity a generation ago. They adapted in utero to expect such austerity in later life, only to find this did not occur; diabetes and obesity were the results. This is the 'thrifty foetus' hypothesis.

The debate between the proponents of the two theories is more than academic. At present the only way of treating the type of diabetes affecting these people is by enforcing a strict diet, which for many sufferers has proved impossible. Knowing the root cause of the disorder, however, could eventually lead to a cure - or at least effective prevention.

The type of diabetes found in Nauru and elsewhere in Asia and North America is known as type-2. Unlike type-1, it usually strikes in adulthood. One of the main symptoms is wildly fluctuating blood sugar levels, but scientists are not sure exactly why. Sufferers seem to overproduce the hormone insulin - made in the pancreas - in early life, then suffer a form of resistance to it later on. One of the traits is that food energy is readily converted into fat rather than being burned off or excreted; serious medical disorders such as blindness, kidney problems, heart ailments and gallstones

soon follow.

On the island of Nauru, this form of diabetes affects about 60 per cent of older adults, compared to a level of a few per cent in Europeans. Jared Diamond, an anthropologist at the University of California at Los Angeles, has written: 'The disease now contributes to most non-accidental deaths on Nauru, with the paradoxical result that wealthy Nauru has one of the world's shortest human lifespans.'

Geneticists see the situation on Nauru as an example of the thrifty genotype hypothesis first suggested more than 30 years ago by Jim Neel, of the University of Michigan at Ann Arbor. In 1962, he said in a seminal scientific paper that diabetics have 'a 'thrifty' genotype, in the sense of being exceptionally efficient in the intake and/or utilisation of food'. It must be remembered, he added, that for our ancestors who existed as hunters and gatherers, it was often a case of 'feast or famine'. Having a 'quick insulin trigger' (which could quickly store blood glucose) would be an advantage for people with such a lifestyle. When exposed to a high-calorie Western diet, however, such thrifty genes result in the overproduction of insulin. Eventually the body becomes 'resistant' to the hormone, perhaps because of its abundance. Diabetes is the result.

Professor Neel's hypothesis has the support of a growing number of scientists, including Kenneth Weiss, a leading American anthropologist and geneticist who has made a study of the diabetes epidemic in North American Indians. 'We found that American Indians had suffered an explosive epidemic that had stayed once it had got there,' he says. Before the Second World War, obesity and diabetes were rare among the native tribes of America. Travellers' descriptions, paintings and early photographs of American Indians during the 19th and early 20th centuries give a generally consistent picture of lean, healthy individuals.

'Clearly there has been a recent environmental influence,' Professor Weiss says, 'probably a change in diet. You just don't get genetic change this fast. But there seems to be a genetic specificity in terms of the fulminating nature of this problem within the American Indian population.'

The American natives, he believes, suffer a genetic susceptibility which is interacting with something in the environment, probably diet. Attempts to find these susceptibility genes, however, have so far failed. 'We have done some genetic work in the American Indian population, but we have come up dry so far.'

This failure to find the susceptibility genes for diabetes is cited by critics as evidence that the 'thrifty genotype' hypothesis cannot be correct. Professor Weiss retorts that the diabetes genes may be hard to isolate because they are so frequent in the populations under study. 'It's like looking for genes for skin colour in a population of Scandinavians,' he says. 'You can't, because they are all pale.'

John Clegg, a geneticist at the Institute for Molecular Medicine at Oxford, believes it should be possible to assess whether known genes involved in the metabolism of glucose are implicated in the diabetes epidemic. 'Once you've got a candidate gene, or genes, it's then very easy to go back to a population and look for specific polymorphisms (mutations) within those populations.' If the thrifty genotype hypothesis is true, the same genetic mutations should be rare or absent in modern Europeans (who generally have a low level of type-2 diabetes). 'They may well have arisen in Europeans, but Europeans have had a much better diet for longer. Because these genes are so deleterious, once they start acting against you they quickly get wiped out by natural selection.'

An intriguing aspect of the thrifty genotype hypothesis is that the ancestors of today's diabetes sufferers - who are mostly of Asian descent - must have endured periods of near starvation which ensured that only people with thrifty genes survived. The ancestors of Nauru, like many Pacific islanders, must have arrived on their islands after travelling long distances in canoes, with only those carrying thrifty genes surviving the enormous privations of the journey. Similarly, the ancestors of today's North American Indians entered the continent across a land bridge of what is now the Bering Strait. In this harsh Arctic climate, says Professor Weiss, the requirement would have been for genes that were efficient in metabolism or energy storage, or could use sources of energy other than carbohydrate. 'But this is all hypothesis, until we can identify the genes.'

This, however, is only grist to the mill of the opponents of the idea. 'The thrifty genotype hypothesis is a hypothesis,' says David Baker, an epidemiologist at the University of Southampton. 'The real answer is: if it's a gene, show me the gene.' As one of the chief architects of the 'thrifty foetus' alternative, he believes he has hard evidence to back up his claims. He argues that the diabetes epidemic around the world is due to what happened in the wombs of pregnant women a generation ago. It was then that the foetuses of women living in a low- nutrition environment began to adapt to what should have been a similar environment for them in later life.

Professor Baker explains that insulin in the foetus controls growth. 'If a baby does not grow because it cannot get the food supply through the placenta, then one of the organs that suffers is the pancreas and with it the capacity to make insulin.' At the same time, if growth is being limited because of poor nutrition, the foetus may well become resistant to insulin because it has to tone down its 'let's grow' signal.

These two features - insulin deficiency because of an underdeveloped pancreas, and insulin resistance - are symptomatic of type-2 diabetes, Professor Baker explains. He and his colleague Nick Hales at Cambridge University have trawled through the records of births occurring in Hertforshire since 1911, and have found that the largest babies are the ones least likely to develop diabetes in later life. They believe this is clear evidence that poor nutrition - resulting in smaller babies - is linked with the poor development of the pancreas and the subsequent onset of type-2 diabetes. It is the foetus rather than the genes, Baker and Hales argue, that is controlling the epidemic.

This should not be suprising. 'It has been calculated,' says Professor Baker, 'that in developing into a full-term infant, the fertilised ovum goes through some 42 rounds of cell division. Adverse influences, in particular poor nutrition, acting at this early time could permanently impair the size and structure of the organs and the tissues.'

If the thrifty foetus hypothesis is correct, the epidemic of diabetes and obesity should be transitory - as long as today's pregnant women in these areas of the world are eating well. But this has not been the case for North American Indians, says Professor Weiss, a fact which he believes adds weight to his preferred thrifty genotype theory. Among them, he argues, the prevalence of diabetes is rising.

Back in the thrifty foetus camp, Professor Baker believes this is because the people in these parts of the world are still not eating a healthy diet - only one that is loaded with calories. 'If there is genuine improvement in nutrition,' he says, 'then foetal growth will eventually improve and the scenario for type-2 diabetes will go away. But you cannot say that the transition from short thin people to short fat people is the transition from poor to good nutrition. It isn't'

He remains adamant that early foetal development, rather than a gene 'for' diabetes, is the root cause of the world-wide epidemic. 'It's a law of biology that living things in their early stages respond to their environment. If you put plants in bad soil, they don't grow enormous; they grow small. This adaptation of an early growing thing is a universal of all living things, and the human is no exception.'