SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Obesity is a rapidly growing global problem. It is not simply the result of eating too much, and not all types of obesity have the same significance. Obesity is in part genetic, and one particularly important genetic type of obesity is the tendency to ‘truncal obesity’,—that is, a raised waist-to-hip ratio. Such obesity is powerfully associated not only with a tendency to diabetes, but also to cardiovascular disease, (‘Syndrome X’). Interestingly, this is the type of obesity seen in every hunter–gatherer (HG) population around the globe. Such people are intolerant of carbohydrate, especially refined carbohydrate, especially in the excessive amounts typically consumed in affluent societies. In such pure HG communities, rates of diabetes can be as high as 50%, when the ‘Western’ lifestyle is adopted. Many of us, however, share some of their genes and their carbohydrate intolerance—perhaps as many as 20 or 30% of the world’s population. Pregnancy can uncover this characteristic, and obesity and glucose intolerance in pregnancy are rapidly burgeoning problems. Quite contrary to the common nutritional dogma of encouraging regular carbohydrates, it is suggested that pregnant women with a high waist-to-hip ratio should be strongly advised to adhere to a low-glycaemic-index diet. Additionally, many dietary interventions, some of them derived from observation of HG populations, are of proven benefit in reducing the expression of glucose intolerance and may well help in tackling the obesity epidemic.


Obesity is a growing problem

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Obesity is a serious global epidemic. To quote the European Taskforce:1‘Estimates suggest that 1.1 billion adults are overweight, 312 million of whom are obese. The prevalence of obesity has doubled or tripled in less than two decades, while in children this is rising at an even faster rate’. The same problem is appearing in all developed countries.2,3 Amidst a host of complications that result, of particular concern to this article is the effect of obesity and glucose intolerance in pregnancy.

Obesity is not just eating too much

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Some people are fat because they eat too much and exercise too little. But is all obesity of one type, related to this one combination? And is there just one solution? Why are some people like stick insects, whatever they eat? Why does weight not vary for some people, despite dietary fluctuation? In famine, why do some children develop marasmus more quickly than others? Why are women with polycystic ovary syndrome (PCOS) often plump? Most interestingly, why is truncal obesity of such distinct prognostic significance, compared to more generalised fatness?4,5

Clearly, the calories-to-exercise ratio is only part of the story, and later in the article the idea is explored that the ability to burn off excess calories as heat is an important safeguard against obesity. In part, this is genetically determined, and in part it can be influenced by what we eat. Thus certain types of calories in certain people may be doubly damaging—the burden of the calories, plus the metabolic effect of that food in slowing heat production.

Obesity is in part genetic

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Much is known in relation to the causes of obesity, but many pieces of the jigsaw are still missing. It is clear that some of the factors have a genetic origin, which might find expression in a number of ways: some people may for instance have genetically determined modification of the obesity-related structures—for instance, the hypothalamic hunger centre or satiety centre.6 Production of enzymes is in part genetically determined, and some enteric hormones influence obesity e.g. cholecystokinin produces satiety,7 and ghrelin stimulates appetite.8 There is a complex interaction of glucagon, insulin and blood sugar level that has a profound effect not only on satiety, but also on metabolism.9,10

Other more subtle genetic factors influencing glucose tolerance include control of the ‘carboxypeptidase E’ system. This enzyme is necessary for the breakdown of neuropeptide Y,11 and genetic mutations are associated with middle-age, truncal obesity and glucose intolerance. Chromosome 19 is increasingly quoted as being the locus of some of the hereditary tendency to glucose intolerance.

Leptin production is also in part genetically determined. Leptin is made by adipocytes—the more fat you have, the more leptin you produce.12 Leptin stimulates ‘nucleopeptide Y’, which suppresses appetite.23 Importantly, it also stimulates an increase in basal metabolic rate (BMR). A relative paucity therefore leads to the genetic tendency to obesity. Production of the leptin receptor is also genetically mediated.

Types of obesity, waist–hip ratio, and hunter–gatherers

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Furthermore, not only is it the case that women may be genetically programmed to be obese, but also that the programming might be for one of two main types of obesity: general fatness of female distribution (breasts, bottom, thighs, upper arms) or alternatively ‘truncal obesity’. Truncal (also called ‘central’) obesity is where the fat deposition is mainly around the abdomen and the viscera. This produces a large waist in relation to hip size—i.e. a large waist-hip ratio (WHR).13,14

It is now abundantly clear that such a distribution of fat is associated with both diabetic tendency14,15 and with increased cardiovascular mortality,16–20 (‘Syndrome X’21). The evidence is also powerful that such a tendency is in part genetic22,23 and that even in utero influences begin to exert an effect on expression of the tendency.24,25 Indeed, whole populations can share this tendency. HGs, for instance, are mainly not obese when they live their traditional lifestyle. When such people are exposed to high, refined carbohydrate intake; however, they develop truncal obesity and a vastly increased risk of diabetes—up to 50% in some populations. This tendency to a high WHR and to carbohydrate intolerance is shared by all hunter–gatherer (HG) populations throughout the world: Canadian Inuit, Native Americans, Mexican Indians, Pima Indians, South American Indians, Middle-Eastern Nomads, African Pygmies, Australian Aborigines, Maoris, South Sea Islanders, etc..26–43

Evolutionary and carbohydrates

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Homo sapiens evolved into its modern form 100 000 to 200 000 years ago. At that time, all of the species were HGs. About 20 000 years ago, agriculture was begun, and more stable populations evolved, with (presumably) different genetic tendencies favoured. Some populations stayed as HGs (and have continued as such to this day), but the ‘agriculturalists’ began to grow cereals as well as herd livestock. For these people, the amount of carbohydrate in an average diet increased from very little, to about 30% of the dietary energy intake.44–51 Over the centuries, as populations grew, this proportion gradually increased for the agriculturalists because cereal staples could be grown cheaply, and stored, and so would help stave off starvation for the poorest people in these cultures.

However, for the well fed, it is only in the last half century that there has been a sudden explosion in eating carbohydrates as the major component of the diet. Not only that, but the ‘carbs’ are now being eaten in a much more refined form and in excess of need.52 Even vegetables such as pea and carrot have been bred to be sweeter.15 In evolutionary terms, the pace of change is staggering. For instance, between 1990 and 2000, the amount of potato in the UK, which was processed to produce starch (to make crisps, etc.) increased from 50 to 90%.

The result has been a major challenge to the human genotype—and much more of a challenge to those who are genetically HGs. Few of us can even trace our origins three hundred or four hundred years, so it would be folly to assume that because we do not hunt and gather now, that we are not of that genotype. The evidence is in the waistline: the average waist size of a female in the reproductive years went up by 8 inches between 1950 and 2000.

HG genotype, PCOS, and evolutionary advantage

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

What could be the evolutionary value in glucose intolerance and truncal obesity? It is important to remember that HGs naturally eat very little carbohydrate. If, eating carbohydrate were to ‘turn down the thermostat’ of their metabolism, they would become energy efficient—the ‘thrifty genotype’.53,54 Deposition of truncal and visceral fat would then lower the energy needs. This might be useful if the next meal were 20 miles away. If this meant that they did not produce as much heat, this may well not matter in many climates. Presumably there might also be related advantages to turning up the metabolic burner after a fatty meal.

It is interesting to speculate whether women with polycystic ovaries—who form 20% of the population—are a subgroup of HGs! Certainly, they share the tendency to truncal obesity, glucose intolerance, and increased cardiovascular risk. If, indeed, PCOS is part of the same genotype, then it can be imagined that the tendency not to menstruate or be fertile in times of plenty would be an advantage, if such women became fertile in times of meagre food supplies, when the less energy-efficient women were beginning to become amenorrhoeic.

The inescapable fact, however, is that in the 21st century, at least one-fifth of women (and quite possibly many more) have a genetic tendency to glucose intolerance and yet live in a culture of refined carbohydrate bombardment.

Diet, refined carbohydrates, and truncal obesity

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Therefore, it is possible to be genetically programmed to have truncal obesity—given the right environmental circumstances—and this tendency can be counter-balanced by the systems in the body which, if activated, can suppress appetite, increase BMR, and favour wasteful heat production.

It may be that many environmental and lifestyle factors could influence these systems—e.g. smoking, stress, exercise, and alcohol consumption. Of vital interest, however, is the effect of diet on heat production and thus on the expression of truncal obesity.

The Atkins diet55 famously postulated the severe view that complete exclusion of carbohydrates (inasmuch as that is possible) has a profound effect on metabolic ‘wasting’ of excess energy—so profound in fact, that dietary fat can be eaten with alacrity. Too much carbohydrate in the diet is bad for some people, especially those with a tendency to glucose intolerance.56 Furthermore, reduced carbohydrate in the diet has been shown to have beneficial effects in certain circumstances.57–64

But carbohydrate has less than half the calories of fat, gram for gram, so how can it be more fattening?

Carbohydrates, exercise, and heat production

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

The answer lies in the effect of carbohydrates on heat production. It is incontrovertible that exercise is a vital and effective part of any weight-loss programme.65 Take in 3000 calories and burn off only 2000, and the rest will be stored as fat. Exercise is an important stimulant to this burning. However, regular gym visitors find it dispiriting to realise that the 20 minutes just spent on the rowing machine barely burns enough calories to cover the last packet of crisps.

However, exercise has an added effect on calorie consumption, over and above the calories used in the activity. Aerobic exercise promotes an upregulation of metabolism. The work itself produces heat as a by-product, which the body dissipates by peripheral vasodilation. However, the vasodilation does not necessarily close down immediately. As heat continues to be lost, the body is capable of short-circuiting the need for energetic exercise by allowing fat to be burnt directly to heat production, rather than to production of high-energy phosphates.66,67 This occurs in infants, for instance, by activation of ‘mitochondrial uncoupling protein’ in brown adipocytes (under adrenergic stimulation).68 This is a considerably more wasteful use of the energy in fat than providing energy for work. By analogy, a litre of petrol will take half a ton of car 5 or 6 miles. Thrown on a fire, however, the same litre will produce a very temporary burst of heat.

Thus, exercise is an important trigger to the key element of weight control—heat production. Anything, which influences this metabolic process will also affect weight. Thus, dietary carbohydrate in HGs might not only cause the tendency to obesity (and glucose intolerance) by excess calories, but also by a downregulation of metabolism.

Carbohydrates and glycaemic index

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

It seems unlikely, however, that all carbohydrate is always bad, for all people. Certainly, it has long been held that a healthy diet should include five portions of fruit and vegetable,69,70 and many fruit and some vegetables are rich in carbohydrate. However, the effect of the carbohydrate in its complex, natural form on insulin metabolism is dependent on the type of carbohydrate. Oats and pearl barley, for instance, have less readily available carbohydrate, and so are said to have a lower ‘glycaemic index’ (GI).71 Even the species of plant can make a difference—the (durum) wheat used for pasta has a lower GI than that used for bread, for instance. The type of food processing also influences the GI—wholemeal bread, for example, has almost the same GI as white bread, because the preparation of the flour makes the carbohydrate more readily available. Whole-grain bread, however, has a significantly lower GI, and also contains natural vitamins, of which grains are an important source.72

A study of the GI of foods can be surprising and enlightening. The ubiquitous potato, for instance, comes off badly. When peeled, it adds very little to the diet except energy and stomach filling73,74—and carbohydrates filling the stomach do not produce the same degree of satiety as fats.75 When baked in its jacket, the situation is no better. True, it is low in fat, but the vitamins are destroyed, and the GI significantly elevated by the baking, such that the result is almost pure starch.

It seems very sensible to suggest, therefore, that women with a tendency to glucose intolerance should limit the total amount of carbohydrate they eat, and what they do take should be of a complex, whole-grain,76 low-GI form.

Dietary manipulation and glucose intolerance

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

Interestingly, it is not only the GI of food, which can affect glucose tolerance. Numerous foods and supplements have been shown to have significant benefit in reducing insulin resistance in susceptible individuals. Much information has come from studying the diet of HGs, which is naturally anti-diabetic.

HGs often eat fish as a major nutrient, and fish oil contains varying amounts of omega-3 fatty acids,77–79 (n-3FA), which seem to decrease insulin resistance and increase BMR. N-3 FA are types of poly-unsaturated fatty acids, but other fats can also affect glucose tolerance—e.g. substituting mono-unsaturated fatty acids for carbohydrates in the diet reduces insulin resistance.80–82 Given the multifaceted nature of insulin resistance, if any single intervention can be shown to make a difference by itself, then that intervention should be worthy of close scrutiny, even if it is a nutrient.

Chromium (Cr) seems to be a particularly important supplement for those with insulin resistance. Dietary Cr intake is poor in the UK (few people achieve the recommended allowance of 50 mg per day) and a diet high in refined carbo hydrate (CHO) causes a large increase in Cr excretion. Supplementing Cr in such people significantly improves insulin resistance.83–90

Soluble fibre in foods binds CHO in the gut and thus improves glucose metabolism.15 This may be the mechanism whereby certain foodstuffs have proven to have anti-diabetic qualities, despite the CHO content. Examples include Korean ginseng,91 flax seed,92 fenugreek,93 and many other plant products.94–100 The addition of folic acid and anti-oxidants to the diet have benefits not only for CHO metabolism, but also for the raised CV risk of glucose intolerant people (e.g. by reduction of homocysteine levels).

Some natural diets put many of these elements together—for instance the ‘Mediterranean diet’101—and this significantly benefits cardiovascular mortality.102 Fish seems to be a particularly important component of such diets,103 and meat fat seems to be bad.14

Does it matter?

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

If some parts of the population have a genetic tendency to truncal obesity and glucose intolerance, which finds expression when they exercise little and eat the wrong foods, does this matter?

Emphatically, yes! It matters firstly to the woman’s long-term health. Her life expectancy is considerably truncated in proportion to the degree of truncal obesity.104,105 The extra weight carried causes additional health problems such as degeneration of joints and complications of surgery.

It matters further because glucose intolerance is related to significantly higher levels of infertility and miscarriage, both of which improve with weight loss.106–112

And it matters because perinatal mortality is considerably increased in the presence of glucose intolerance.113 Fetal anomaly114 is only one aspect of this—in the West Midlands in 2004, one-third of perinatal deaths occurred in women with a body mass index over 30,115 (22% of the population—and rising). We simply do not fully understand the effects of borderline,and often undetected, glucose intolerance on the metabolism and development of the fetus.

Summary

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

So the message is clear: a high WHR is common, is in part genetically determined, is associated with glucose intolerance, which is exacerbated by pregnancy,116 and is modifiable by lifestyle interventions. It is made worse by high, refined carbohydrate in the diet and by lack of exercise, both of which are endemic in the UK.

Allowed to go its own way, it is bad for reproductive health, for any children a woman may bear, for her life expectancy, and for her general health.

What can be done?

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References

I make a simple suggestion. Adult women should measure their WHR, and should have it measured for them at booking antenatal visits and other appropriate opportunities. The higher it is above the accepted upper limit (0.85), the more they should be advised to be on a low-GI diet (which has no known downsides, except in famine). They should restrict the total proportion of carbohydrate in the diet, and what carbohydrates they do eat should be in the complex, whole grain, low-GI form.

Glucose intolerance should be screened for in pregnancy,117 and if found, it is worth considering supplementation with omega-3 fatty acid, chromium, and folic acid. Other supplements are also quite possibly of benefit, including garlic, Korean ginseng, and flax seed oil. (Some proprietary preparations, e.g. Vitabiotic’s ‘CardioACE’—contain many of these ingredients—n-3FA, folic acid, garlic, chromium, anti-oxidants, etc.). It would also help women to know which fruit and vegetables were relatively ‘anti-diabetic’ (e.g. parsnip and turnip), and which were pro-diabetic, e.g. potato.

However, the message can be put more simply: if you have a fat waist, then cut the carbs!

References

  1. Top of page
  2. Abstract
  3. Obesity is a growing problem
  4. Obesity is not just eating too much
  5. Obesity is in part genetic
  6. Types of obesity, waist–hip ratio, and hunter–gatherers
  7. Evolutionary and carbohydrates
  8. HG genotype, PCOS, and evolutionary advantage
  9. Diet, refined carbohydrates, and truncal obesity
  10. Carbohydrates, exercise, and heat production
  11. Carbohydrates and glycaemic index
  12. Dietary manipulation and glucose intolerance
  13. Does it matter?
  14. Summary
  15. What can be done?
  16. References
  • 1
    James PT, Rigby N, Leach R. International Obesity Task Force. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004;11:38.
  • 2
    James PT, Leach R, Kalamara E, Shayeghi M. The worldwide obesity epidemic. Obes Res 2001;9:S22833.
  • 3
    Katzmarzyk PT. The Canadian obesity epidemic, 1985–1998. CMAJ 2002;166:103940.
  • 4
    Snijder MB, Van Dam RM, Visser M, Seidell T. What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol 2006;35:8392.
  • 5
    Koh-Banerjee P, Chu N-F, Spiegelman D, Rosner B, Colditz G. Willett W, et al. Prospective study of the association of changes in dietary intake, physical activity, alcohol consumption, and smoking with 9-y gain in waist circumference among 16 587 US men. Am J Clin Nut 2003;78:71927.
  • 6
    Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab 1995;80:5739.
  • 7
    Miyasaka K, Kanai S, Ohta M, Kawanami T, Kono A, Funakoshi A. Lack of satiety effect of cholecystokinin (CCK) in a new rat model not expressing the CCK-A receptor gene. Neurosci Lett 1994;180:1436.
  • 8
    Moran LJ, Noakes M, Clifton PM, Wittert GA, Tomlinson L, Galletly C, et al. Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not differentially affected by diet composition. J Clin Endocrinol Metab 2004;89:333744.
  • 9
    Geary N. Pancreatic glucagon signals postprandial satiety. Neurosci Biobehav Rev 1990;14:32338.
  • 10
    Debons AF, Krimsky I, From A, Cloutier RJ. Rapid effects of insulin on the hypothalamic satiety center. Am J Physiol 1969;217:111418.
  • 11
    Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF. Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 1986;7:118992.
  • 12
    Harvey J, Ashford MLJ. Leptin in the CNS: much more than a satiety signal. Neuropharmacology 2003;44:84554.
  • 13
    Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of type 1 diabetes—the analysis of the data on published incidence trends. Diabetologia 1999;42:1395403.
  • 14
    American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. Diabetes Care 1994;17:51922.
  • 15
    Leigh Broadhurst C. Nutrition and non-insulin dependent diabetes mellitus from an anthropological perspective. Altern Med Rev 1997;2:37899.
  • 16
    Haffner SM. Obesity and the metabolic syndrome; the San Antonio Heart Study. Br J Nutr 2000;83 (Suppl 1):S6770.
  • 17
    King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:141431.
  • 18
    Centers for Disease Control and Prevention. National diabetes fact sheet, United States, 2003. Atlanta, GA: Centers for Disease Control and Prevention; 2004.
  • 19
    Hogan P, Dall T, Nikolov P. American Diabetes Association. Economic costs of diabetes in the US in 2002. Diabetes Care 2003;26:91732.
  • 20
    Arredondo A, Zuniga A. Economic consequences of epidemiological changes in diabetes in middle-income countries. The Mexican case. Diabetes Care 2004;27:1049.
  • 21
    Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: more than just Syndrome X. Comp Biochem Physiol A Mol Integr Physiol 2003;136:95112.
  • 22
    Pérusse L, Chagnon YC, Weisnagel J, Rankinen T, Snyder E, Sands J, et al. The human obesity gene map: the 2000 update. Obesity Res 2001;9:13569.
  • 23
    Elbein SC. The genetics of human noninsulin dependent (type 2) diabetes mellitus. J Nutr 1997;127:1891S96S.
  • 24
    Pettitt DJ, Aleck KA, Baird HR, Carraher MJ, Bennett PH, Knowler WC. Congenital susceptibility to NIDDM. Role of intrauterine environment. Diabetes 1988;37:6228.
  • 25
    Dabelea D, Pettitt DJ. Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab 2001;14:108591.
  • 26
    O’Keefe JH, Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin Proc 2004;79:1018.
  • 27
    TruswellAS, editor. Diet and nutrition of hunter-gatherers. In: Ciba Foundation Symposium 49. Health and Disease in Tribal Societies. New York: Elsevier; 1977. p. 21326.
  • 28
    Dowse GK, Spark RA, Mavo B, Hodge AM. Extraordinary prevalence of non-insulin-dependent diabetes mellitus and bimodal plasma glucose distribution in the Wanigela people of Papua New Guinea. Med J Aust 1994;160:76774.
  • 29
    Cockram Clive S. Diabetes mellitus: perspective from the Asia–Pacific region. Diabetes Res Clin Pract 2000;50(Suppl 2):S37.
  • 30
    Clastres P. The Guayaki. In: BiccheriM, editor. Hunters and Gatherers Today. New York: Holt, Rinehart, and Winston, Inc; 1972. p. 13874.
  • 31
    Junshi C, Campbell TC, Junyao L, Peto R. Diet, Life-style, and Mortality in China. UK: Oxford University Press; 1990.
  • 32
    McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991;337:3826.
  • 33
    O’Dea K, Patel M, Kubisch D, Hopper J, Traianedes K. Obesity, diabetes and hyperlipidaemia in a Central Australia Aboriginal community with a long history of acculturation. Diabetes Care 1993;16:100410.
  • 34
    Roosevelt AC, Lima de Costa M, Lopes Machado C, Michab M, Mercier N, Valladas H, et al. Paleoindian cave dwellers in the Amazon: the peopling of the Americas. Science 1996;272:37384.
  • 35
    Salzano FM, Callegari-Jacques SM. South American Indians: A Case Study in Evolution. Oxford: Clarendon Press; 1988.
  • 36
    NeelJV, editor. Health and disease in unacculturated Amerindian populations. In: Ciba Foundation Symposium 49. Health and Disease in Tribal Societies. New York: Elsevier; 1977. p. 15577.
  • 37
    Milton K. Protein and carbohydrate resources of the Maku indians of northwestern Amazonia. Am Anthropol 1984;86:727.
  • 38
    Martorell R. Diabetes and Mexicans: why the two are linked. Prev Chronic Dis 2005;2:A04.
  • 39
    Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians. J Matern Fetal Med 2000;9:838.
  • 40
    Szathmary EJE. Non-insulin dependent diabetes mellitus among aboriginal North Americans. Annu Rev Anthropol 1994;23:45782.
  • 41
    Robinson EJ, Gebre Y, Pickering JL, Petawabano B, Superville B, Lavallée C. Effect of bush living on aboriginal Canadians of the Eastern James Bay region with non-insulin-dependent diabetes mellitus. Chronic Dis Can 1995;16:1448.
  • 42
    Ebbesson SO, Schraer CD, Risica PM, Adler AI, Ebbesson L, Mayer AM, et al. Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations: the Alaska-Siberia Project. Diabetes Care 1998;21:5639.
  • 43
    Dowse GK, Zimmet PZ, Finch CF, Collins VR. Decline in incidence in epidemic glucose intolerance in Nauruans: implications for the ‘thrifty genotype’. Am J Epidemiol 1991;133:1093104.
  • 44
    Miller J, Colagiuri S The carnivore connection: dietary carbohydrate in the evolution of NIDDM. Diabetologia 1994;37:12806.
  • 45
    Mann AE. Diet and human evolution. In: HardingRSO, TelekiG, editors. Omnivorous Primates. New York: Columbia University Press; 1981. p. 1036.
  • 46
    Speth JD, Spielmann KA. Energy source, protein metabolism, and hunter-gatherer subsistence strategies. J Anthropol Archaeol 1983;2:131.
  • 47
    Cordain L, Brand-Miller J, Eaton SB, Mann N, Holt SH, Speth JD. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherers. Am J Clin Nutr 2000;71:68292.
  • 48
    Cassidy CM. Nutrition and health in agriculturalists and hunter-gatherers: a case study of two prehistoric populations. In: JeromeNW, KandelRF, PeltoGH, editors. Nutritional Anthropology: Contemporary Approaches to Diet and Culture. Pleasantville, NY: Redgrave Publishing Co; 1980. p. 11745.
  • 49
    Cordain L. The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. J Am Neutraceut Assoc 2002;5:1524.
  • 50
    Cordain L, Eaton SB, Miller JB, Mann N, Hill K. The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr 2002;56(Suppl 1):S4252.
  • 51
    Altar T. What might be the ‘natural’ diet of human beings? 1994 [http://arrs.envirolink.org/ar-voices/natural_diet.html]. Accessed January 2006.
  • 52
    Nutrient and energy intakes for the European community. 31st Series Reports of the Scientific Comittee for Food. Directorate-General Internal Market and Industrial Affairs. Luxemberg: Office for Official Publications of the European Community, 1992: p. 529.
  • 53
    Neel JV, Weder AB, Julius S. Type II diabetes, essential hypertension, and obesity as ‘syndromes of impaired genetic homeostasis’: the ‘thrifty genotype’ hypothesis enters the 21st century. Perspect Biol Med 1998;42:4474.
  • 54
    O’Dea K. Clinical implications of the ‘thrifty genotype’ hypothesis: where do we stand now? Nutr Metab Cardiovasc Dis 1997;7:2814.
  • 55
    Atkins RC. Dr. Atkins’ The New Diet Revolution. New York, NY: Avon Books; 1998.
  • 56
    Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. The third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998;21:51824.
  • 57
    Baba NH, Sawaya S, Torbay N, Habbal Z, Azar S, Hashim SA. High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord 1999;23:12026.
  • 58
    Leeds AR. Glycemic index and heart disease. Am J Clin Nutr 2002;76:286S9S.
  • 59
    Parker B, Noakes M, Luscombe N, Clifton P. Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 2002;25:42530.
  • 60
    Wolfe BM, Giovannetti PM. Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human subjects. Metabolism 1991;40:33843.
  • 61
    Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, et al. A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. J Nutr 2003;133:41117.
  • 62
    O’Dea K, Traianedes K, Ireland P, Niall M, Sadler J, Hopper J, et al. The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes. J Am Diet Assoc 1989;89:107686.
  • 63
    Torbay N, Baba NH, Sawaya S, Bajjani R, Habbal Z, Azar S, et al. High protein vs high carbohydrate hypoenergetic diet in treatment of obese normoinsulinemic and hyperinsulinemic subjects. Nutr Res 2002;22:58798.
  • 64
    Wolfe BM, Piche LA. Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects. Clin Invest Med 1999;22:1408.
  • 65
    Wing RR. Physical activity in the treatment of the adulthood overweight and obesity: current evidence and research issues. Med Sci Sports Exerc 1999;31(Suppl):S54752.
  • 66
    Westerterp-Plantenga MS, Rolland V, Wilson SA, Westerterp KR. Satiety related to 24 h diet-induced thermogenesis during high protein/carbohydrate vs high fat diets measured in a respiration chamber. Eur J Clin Nutr 1999;53:495502.
  • 67
    Flatt J-P. Use and storage of carbohydrate and fat. Am J Clin Nutr 1995;61:952S9S.
  • 68
    Bachman ES, Dhillon H, Zhang C-Y, Cinti S, Bianco AC, Kobilka BK, et al. BetaAR signaling required for diet-induced thermiogenesis and obesity resistance. Science 2002;297:8435.
  • 69
    Subar AF, Heimendinger J, Patterson BH, Krebs-Smith SM, Pivonka E, Kessler R. Fruit and vegetable intake in the United States: the baseline survey of the Five A Day for Better Health Program. Am J Health Promot 1995;9:35260.
  • 70
    Joshipura KJ, Hu FB, Mason JE, Stampfer MJ, Rimm EB, Speizer FE, et al. The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med 2001;134:110614.
  • 71
    Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287:241423.
  • 72
    Crapo PA. Simple versus complex carbohydrates in the diabetic diet. Annu Rev Nutr 1985;5:95114.
  • 73
    Hermansen K, Rasmussen O, Arnfred J, Winther E, Schmitz O. Differential glycaemic effects of potato, rice and spaghetti in Type 1 (insulin-dependent) diabetic patients at constant insulinaemia. Diabetologia 1986;29:35861.
  • 74
    Schefrin R. Good carbs Bad carbs, Today’s Dietician, 2003 April. p. 14.
  • 75
    Stubbs RJ. Macronutrient effects on appetite. Int J Obes Relat Metab Disord 1995;19(Suppl 5):S1119.
  • 76
    Hallfrisch J, Behall KM. Mechanisms of the effects of grains on insulin and glucose responses. J Am Coll Nutr 2000;19:320S25S.
  • 77
    Eritsland J, Seljeflot I, Abdelnoor M, Arnesen H, Torjesen PA. Long-term effects of n-3 fatty acids on serum lipids and glycaemic control. Scand J Clin Lab Invest 1994;54:27380.
  • 78
    DrevonCA, BaksaasI, KrokanHE, editors. Omega 3 Fatty Acids: Metabolism and Biological Effects. Basel: Birkhauser Verlag; 1993.
  • 79
    O’Keefe JH Jr, Harris WS. From Inuit to implementation: omega-3 fatty acids come of age. Mayo Clin Proc 2000;75:60714.
  • 80
    Campbell LV, Marmot PE, Dyer JA, Borkman M, Storlien LH. The high-monounsaturated fat diet as a practical alternative for NIDDM. Diabetes Care 1994;17:17782.
  • 81
    Sarkkinen E, Schwab U, Niskanen L, Hannuksela M, Savolainen M, Kervinen K, et al. The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance. Eur J Clin Nutr 1996;60:5928.
  • 82
    Christiansen E, Schnider S, Palmvig B, Tauber-Lassen E, Pedersen O. Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids. Diabetes Care 1997;20:8817.
  • 83
    Anderson RA. Recent advances in the clinical and biochemical effects of chromium deficiency. In: PrasadAS, editor. Essential and Toxic Trace Elements in Human Health and Disease: An Update. New York: Wiley-Liss; 1993. p. 22134.
  • 84
    Kozlovsky AS, Moser PB, Reiser S, Anderson RA. Effects of diets high in simple sugars on chromium urinary losses. Metabolism 1986;35:51518.
  • 85
    Anderson RA, Bryden NA, Polansky MM, Reiser S. Urinary chromium excretion and insulinogenic properties of carbohydrates. Am J Clin Nutr 1990;51:8648.
  • 86
    Anderson RA. Nutritional factors influencing the glucose/insulin system: chromium. J Am Coll Nutr 1997;16:40410.
  • 87
    Urberg M, Zemmel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:8969.
  • 88
    Anderson RA, Cheng N, Bryden NA, Polansky MM, Chi J, Feng J. Beneficial effects of chromium for people with Type II diabetes. 56th Annual Meeting of the American Diabetes Association, June 1996, Abstract. Diabetes 1997;46:178691.
  • 89
    Broadhurst CL, Schmidt WS, Anderson RA, et al. Lipids, chromium, and phytochemicals: a synergistic approach to non insulin dependent diabetes mellitus. Essential Fatty Acids and Eicosanoids: Invited Papers from the Fourth International Conference July 1997 [abstract]. Prostaglandins Leukot Essent Fatty Acids 1997;57:202.
  • 90
    Anderson RA. Chromium, glucose tolerance, diabetes and lipid metabolism. J Adv Med 1995;8:3749.
  • 91
    Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 1995;18:13735.
  • 92
    Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, Chen ZY, et al. High a-linoleic flaxseed (linum usitaissimum): some nutritional properties. Br J Nutr 1993;69:44353.
  • 93
    Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:3016.
  • 94
    Liu S. Intake of refined carbohydrates and whole grain foods in relation to risk of Type 2 diabetes mellitus and coronary heart disease. J Am Coll Nutr 2002;21:298306.
  • 95
    Marles RJ, Farnsworth NR. Plants as sources of antidiabetic agents. Econ Med Plant Res 1994;6:14987.
  • 96
    Sanchez de Medina F, Gamez MJ, Jimenez I, Jimenez J, Osuna JI, Zarzuelo A. Hypoglycemic activity of juniper ‘berries’. Planta Med 1994;60:197200.
  • 97
    Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989;12:55364.
  • 98
    Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol 1995;48:2532.
  • 99
    Trejo-Gonzales A, Gabriel-Ortiz G, Puebla-Perez AM, Huizar-Contreras MD, Munguia-Mazariegos MR, Mejia-Arreguin S, et al. A purified extract from prickly pear cactus (Opuntia fuliginosa) controls experimentally induced diabetes in rats. J Ethnopharmacol 1996;55:2733.
  • 100
    Lovejoy JC, Most MM, Lefevre M, Greenway FL, Rood JC. Effect of diets enriched in almonds on insulin action and serum lipids in adults with normal glucose tolerance or type 2 diabetes. Am J Clin Nutr 2002;76:10006.
  • 101
    Curtis BM, O’Keefe JH Jr. Understanding the Mediterranean diet: could this be the new ‘gold standard’ for heart disease prevention? Postgrad Med 2002;112:358, 41–5.
  • 102
    Willett WC, Stampfer MJ. Rebuilding the food pyramid. Sci Am 2003;288:6471.
  • 103
    Kris-Etherton PM, Harris WS, Appel LJ, American Heart Association, Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease [published correction appears in Circulation. 2003;107:512]. Circulation 2002;106:274757.
  • 104
    Visscher TLS, Seidell JC, Molarius A, Van Der Kuip D, Hofman A Witteman JCM. A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study. Int J Obes 2001;25:17305.
  • 105
    Folsom AR, Kushi LH, Anderson KE, Mink PJ, Olson JE, Hong CP, et al. Associations of general and abdominal obesity with multiple health outcomes in older women: the Iowa Women’s Health Study. Arch Intern Med 2000;160:211728.
  • 106
    Wass P, Waldenstrom U, Rossner S, Hellberg D. An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer. Hum Reprod 1997;12:205760.
  • 107
    Zaadstra BM, Seidell JC, Van Noord PA, Te Velde ER, Habbema JD, Vrieswijk B, et al. Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. BMJ 1993;306:4847.
  • 108
    Fat and female fecundity: prospective study of effect of body fat distribution on conception rates [editorial]. BMJ 1993;306:1065.
  • 109
    Hammadeh ME, Sykoutris A, Schmidt W. Relationship between body mass index and reproduction. Curr Womens Health Rev 2005;1:13142.
  • 110
    Crosignani PG, Vegetti W, Colombo M, Ragni G. Resumption of fertility with diet in overweight women. Reprod BioMed Online 2002;5:604.
  • 111
    Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, et al. Weight loss results in significant improvement in pregnancy and ovulation rates in an ovulatory obese women. Hum Reprod 1995;10:270512.
  • 112
    Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13:15025.
  • 113
    Galtier-Dereure F, Boegner C, Bringer J. Obesity and pregnancy: complications and cost. Am J Clin Nut 2000;71:1242S8S.
  • 114
    Waller DK, Mills JL, Simpson JL, Cunningham GC, Conley MR, Lassman MR, et al. Are obese women at higher risk for producing malformed offspring? Am J Obstet Gynecol 1994;170:5418.
  • 115
    West Midlands Perinatal Mortality Data, West Midlands Perinatal Institute, 2006. [www.perinatal.nhs.uk].
  • 116
    Ford F, Barrowclough D. Pregnancy-associated weight gain – does it contribute to the rising rate of obesity in women in the UK? Nutr Food Sci 2001;31:1838.
  • 117
    SteerP, editor. Screening for gestational diabetes. BJOG 2006;1:1.