Fat, Fate, and Disease : Why we are losing the war against obesity and chronic disease (25 page)

But the babies not only become fat: they are also much more likely to develop diabetes themselves. Recently a large study has been carried out in over 2,300 Chinese people living in Hong Kong. About a quarter of those with diabetes had at least one diabetic parent and this was much more likely to be a diabetic mother than a diabetic father. This effect might have a genetic component, but as we have seen there is little evidence for this. And the fact that it is more commonly transmitted when the mother is the parent with diabetes points to a developmental factor. This is given strong support from the finding that people who developed diabetes were more likely to do so early if their mother had diabetes during pregnancy than if she developed it after they were born. Similar conclusions have been reached from a recent study with Canadian First Nations people, about one in five of whom will develop diabetes; up to a third of these cases can in turn be attributed to their mother having gestational diabetes.

Clearly, being in some way exposed to high levels of glucose as a fetus predisposes a person to develop diabetes later. The arguments have many similarities to those we presented above to explain how maternal obesity has effects on the offspring. Once again it is important to flag up the distinction between processes which are normal, even if they have consequences for risk of disease later, and those which are pathological from the start.

Early pregnancy is a finely balanced physiological situation where the developing embryo and its mother have to come to some agreement about the course ahead. More often than not they do not reach an agreement, because the majority of conceptions—as many as 70 per cent—end in early miscarriage. It may be that the balance between the immune system of the embryo and that of the mother is not right, and this of course will be critical for her to permit what is essentially a foreign being, with up to half its genes
different from hers, growing in her womb for nine months. Or there may be other factors contributing to the incompatibility.

But despite what appears to be a somewhat unstable situation in early pregnancy, once implantation has been achieved and the placenta has been established to nourish the fetus, it actually becomes very hard to abort the fetus. History furnishes many examples of women involved in warfare, famine, flood, or earthquake in early pregnancy who yet successfully carry their fetuses to term. At this time in pregnancy the mother’s resources must be optimally devoted to the development of the fetus—there is now no going back. This makes sense in evolutionary terms. The mother has invested a lot to ensure that her genes are transmitted to the next generation and it is more sensible to keep on investing than to start again. It is a dilemma that anyone who has started building or renovating a house knows well. Even if the architect and builder have grossly underestimated the cost, once you have invested so much you have little choice but to press on—returning to the bank manager yet again.

So why are mothers more likely to get diabetes in pregnancy? Yet again it is a consequence of what is a normal process becoming abnormal because we no longer live as we did thousands of years ago.

Glucose is the most important fuel for the human fetus and once the placenta has developed, it makes special hormones that change the mother’s metabolism, helping to mobilize her own fat stores and to shift her biochemistry to one that consumes more fat and less glucose so that more of this sugar can pass on to her fetus. Even the protein stored in her muscles can be mobilized to provide essential amino acids so that the developing fetus can grow. These placental hormones change the mother’s metabolism by inducing a level of insulin resistance—the state in which her own insulin works less well and akin, at a mild level, to what happens in diabetes.

But if the woman is herself already on the path to insulin resistance before she became pregnant, in pregnancy she is likely to become frankly diabetic—and this is gestational diabetes. We know
that women who get gestational diabetes are more likely to develop diabetes even when they are not pregnant later in their lives, so there is clearly a connection, although it is pregnancy which seems to reveal the underlying problem.

There is a whole range of factors which contribute to women being at greater risk of developing gestational diabetes. Being overweight is one; eating a diet very high in fat and fructose during pregnancy is another. The hormones present during a pregnancy make a woman more sensitive to such a diet, and this effect is superimposed on any genetic and developmental factors that have already influenced her biology to set her risk of developing the condition.

Women who have a poor start to life, as well as those who had a mother with gestational diabetes, are more likely to get gestational diabetes themselves. Gestational diabetes is also more common in women suffering from polycystic ovarian syndrome, and this itself is more common in those who have a poor start to life. So there appear to be cycles of risk passed on from generation to generation by a range of processes.

It is clear that the early identification of diabetes, or potential diabetes, during pregnancy is of utmost importance, and that once identified it needs to be treated highly effectively. All too often doctors are satisfied to find a blood glucose level which appears to be within the normal range or is not too high at a particular point in time, rather than trying to track the day-by-day, and even hour-by-hour, variations in blood glucose in their patients. These swings in glucose can be quite dramatic even if the average level remains within the normal range. It may well be that it is, in fact, these swings that lead to adverse effects on the offspring.

Recent studies have shown that there is very little limit to the passage of glucose across the placenta from the mother to the fetus. This is in striking contrast to some other substances for which passage is clearly very carefully controlled by the placenta. It is almost as if the fetus cannot have too much of a good thing in the form of sugar.
It appears that evolution has led to the selection of mechanisms that defended our ancestors more against the risk of under-nourishing a fetus than of over-nourishing it. We believe that this is because the risk of over-nourishment was remote in times past. This lack of control might have had an advantage during evolutionary history by maximizing the nutrition of the fetus. Indeed because high-energy diets did not exist regularly in our evolutionary past and because, without modern medicine, gestational diabetes carries with it a high risk of fetal death, we would argue that gestational diabetes is not likely to have been a frequent occurrence during our evolution, so we have not evolved protective measures against it.

There is further evidence in support of this argument. The high levels of insulin resulting from the mother’s high blood sugar mean that the baby also needs to run on high blood sugar after birth. This is unlikely to occur because most women do not find it possible to feed their infants abundantly soon after delivery. It is normal for it to take some days—on the first day the breast does not produce normal milk, but what is called colostrum, which is rich in immune proteins and hormones that are of great value to the baby’s health. So blood glucose levels fall more dramatically in the newborn baby of a mother whose diabetes was not well controlled, driven by its high insulin levels, and this can lead to the brain being starved of glucose. The infant may become unconscious or brain damaged, or may even die. This is another reason why gestational diabetes would have been filtered out by evolution.

Starting life with more fat cells means that we have more fat cells for the whole of our life, because once made they stay with us. If we keep to a prudent diet these may not get loaded with fat but, as we have seen, it is hard to stay on a prudent diet in this energy-rich world. Later in life, having cells packed with fat leads to insulin resistance. But if we become insulin-resistant we have to make more insulin to get adequate amounts of glucose into our body’s cells. At some point the pancreas cannot keep
up with this increased demand to make insulin. So we cannot control blood sugar and in time we become diabetic.

Insulin resistance also leads to high blood fat levels and these fats enter the membranes of muscle and liver cells and change the way they work. This makes them more insulin-resistant still, and so the disease process is aggravated. It just gets worse and worse. So children who start life with more fat cells are more likely to get diabetes as they grow up, particularly in the kind of high food-energy world most of us now inhabit.

The key point is that these effects on the fetus are essentially adaptations of the developing organism to what it sees as a normal stimulus. The information it receives from its mother has consequences for its development. We are all, to a greater or lesser degree, adapted to the world in which our ancestors used to live and, as we saw in the last chapter, we try to use developmental plasticity in fetal life to adapt ourselves to the world we expect to live in as we grow up. But this is becoming harder and harder to do as the world that evolution designed us for is very different from the world of industrial agriculture, modern processed foods, and labour-saving devices.

We still think that a fat baby is a healthy baby, when in fact he or she may be on the path to obesity. It is obvious how this perception emerged. In the 19th century a thin baby was probably one who was under-nourished or growth-retarded and at greater risk of getting an infection, or just ‘failing to thrive’ as the phrase went among doctors of the period. Such babies were more likely to die. Measles and other common childhood illnesses could be death sentences for an undernourished child, just as they are today in many developing countries. Sadly, several million children still die each year from under-nutrition and associated illnesses, particularly in Africa and parts of Asia. So as maternal and child health services emerged at the beginning of
the 20th century, a key focus was on ensuring the adequate nutrition of infants. Specially designed infant formulas were developed and promoted at this time, which made it easy to provide infants with more calories than breast milk. So infants grew bigger.

In many parts of the world, bottle-feeding was marketed as socially desirable, convenient, and something which the modern, liberated woman and her partner should do. So, many women started to bottle-feed, and this did indeed help their babies to grow fat—but, regrettably, the beneficial effects of breastfeeding were lost. The tragedy of this emerged in Africa in the 1970s where aggressive marketing of infant formula led well-intentioned mothers to bottle- rather than breastfeed. As formula cannot provide the immune support that breast milk does, and the water used to make up the formula was often not clean, the consequence was epidemic gastroenteritis, which led to thousands of infant deaths. There are now very tight controls on the marketing of baby formula globally, and the major infant food companies generally act responsibly in this regard. Unfortunately this sense of responsibility is not universal, and smaller, nationally based companies can still break the rules—witness the recent tragedy in China where unscrupulous milk producers added melamine to the milk supply to trick buyers into thinking the milk had higher protein levels than it did—but melamine is toxic.

In middle-class Western societies, when women entered the workforce the use of infant formula also became more common. That breastfeeding might be compatible with women’s rights is a very recent concept—but breastfeeding in the workplace is still uncommon and very often hard to maintain. We were slow to recognize the real health benefits of breastfeeding, and there is much more that needs to be done to make it easy and acceptable. We also now know that breastfeeding improves other aspects of the baby’s life in addition to reducing the risk of chronic disease, including maternal–infant bonding, which can lead to improvements in brain development and behaviour.

So mothers and nurses grew up in the first half of the 20th century with the clear view that a fat baby was a healthy one. In the context of their times, that was probably largely correct. But the degrees of fatness have changed and the context of risk has altered dramatically. Just because a well-nourished baby is healthy does not mean that an over-nourished baby is more healthy—indeed he or she will certainly be less healthy in time. As we have seen, there are many reasons why a baby with excess fat may be on the pathway to future disease, but changing the mindset that a fat baby is a healthy baby will take time. Grandmothers might often chide their sons and daughters for allowing their children to be too thin when, provided they are growing, they are in fact fine. Far too many children in Western society are damaged by the baggage of this historically determined cultural perception.

We have seen over the past two chapters that what happens in one generation can influence the next. It has been known for decades that women in the poorest circumstances, who have limited nutrition, give birth to children who become stunted. When their daughters grow up they will, in turn, will give birth to small babies. They will stay like this unless their world changes and energy-dense foods become available in large quantities. Then, as we described in the last chapter, their children are more likely to become mismatched and to be at risk of diabetes or cardiovascular disease. As some women start becoming obese their offspring are at greater risk. As time progresses some of these women will start developing gestational diabetes and yet another pathway to the intergenerational passage of disease risk is set up. In countries such as India, these various intergenerational pathways may operate at the same time. And even in the West, while emaciated mothers giving birth to children who become stunted adults are, thankfully, seldom seen, the other intergenerational pathways exist.

What are the implications of all this for the future? One important implication clearly concerns the mismatch between generations in term of diet. But surely, after the environmental transition has taken place, the situation should be relatively stable? Won’t the increase in obesity and non-communicable disease, which has been so dramatic in many parts of the world, now begin to slow down? The
rate
of rise of childhood obesity is indeed now beginning to slow in some places, but it is still
rising
. Does this mean that we can be optimistic because, while we may perhaps have to suffer the consequences of childhood obesity for the next generation, things will be OK after that?