Several studies indicate that this definition produces an incidence rate of about 24% in the U.S. population [11]. A similar definition by the World Health Organization produces 25% [12]. This average value is deceiving. A recent review [11] finds a strong variation of incidence with both age, body mass and ethnic background. For example, in white males, the prevalence goes from about 15% at age 30 to 40% at age 70, and with white men who are not overweight, prevalence ranges from about 7 to 10%, but if they are obese, the prevalence can reach 75%. It will be noted that the ATP-III definition includes commonly measured or observed parameters obtained during routine physical examinations. It is also important to recognize that there are individuals who are obese but metabolically healthy, i.e. they have none of the attributes of the metabolic syndrome aside from obesity. It may be important to identify this group to avoid inappropriate treatment, to lessen the psychological impact of obesity in these individuals, and to avoid confounding in research studies [13]. However, as discussed below, the health risks associated with obesity may go beyond those related to the metabolic syndrome.

The metabolic syndrome, as defined above, is the latest incarnation of numerous descriptions of a collection of clinical attributes that, according to many studies, lead to greatly increased risks of heart disease and diabetes. Dr. Gerald Reaven [14] of Stanford University is acknowledged as the ground breaker in this fascinating area. The syndrome has also been called Syndrome X, the Metabolic Syndrome X, the Dismetabolic syndrome, and the Deadly Quartet, to name the principal variations on this theme. The importance lies in its association with a large increase in the risk of CHD, CVD, and diabetes. The presence of four or five of the above attributes further increases the risk. It is of interest that LDL cholesterol levels are not included in the ATP-III definition. Part of the reason is that the ATP-III committee is making the metabolic syndrome an independent risk factor over and above elevated LDL. It is interesting in this context that there are those who consider that an elevated triglyceride level coupled with a low HDL cholesterol level may confer at least as great a risk of CHD as an elevated LDL level alone [15,16]. The bottom line is simply that the metabolic syndrome is shockingly prevalent, appears to confer serious risk of CHD and diabetes, and should be taken very seriously by both individuals and their physicians. The relevance to this review is that the metabolic syndrome can be avoided or reversed in many individuals by diet and lifestyle [14].

When the fasting blood glucose level is between 110 and 125 mg/dL (6.1-7.0 mmol/L), the condition is called impaired fasting glucose (IFG). Closely related to IFG is impaired glucose tolerance (IGT). Glucose tolerance is determined by measuring the serum glucose level after giving a fasting patient a drink containing 75 g of glucose, the so-called glucose challenge. At two hours, a blood glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) is regarded as evidence of IGT. In all prevalence studies up to 2002, only half or less of the people with IFG have IGT, and an even lower proportion (20-30%) with IGT have IFG. It is argued that IGT and IFT represent different metabolic disturbances [17], but this is still not clear. The glucose tolerance test, also called the oral glucose tolerance test (OGTT), is not popular, presumably because it requires the patient to wait or revisit the office or clinical lab. Those in favor of the test feel it provides valuable additional information over the fasting glucose measurement [18], whereas those opposed [19] feel that combining the fasting glucose measurement with other clinical observations [20] allows the physician to adequately assess the risks of heart disease and diabetes without "inconveniencing" the patient! However, there is also evidence the OGTT is a better predictor of deaths from all causes as well as CVD as compared to fasting glucose values [21]. The reluctance to do an OGTT is curious considering the serious nature of the problems being investigated. IFG and/or IGT, even as isolated conditions, should be considered warning signals, taken very seriously, and hopefully the recognition would stimulate lifestyle and diet modifications.

Individuals who have IFG or IGT may or may not have what is called insulin resistance, a malfunctioning of the insulin-glucose system wherein abnormally large amounts of insulin are required to maintain blood glucose under control both fasting and after eating. Reaven [14] considers insulin resistance to be at the root of the problems associated with the metabolic syndrome, and to be almost always present when patients present with high triglycerides, low HDL cholesterol, and abdominal obesity. Either the fasting or post glucose challenge insulin level can provide some indication of the presence of insulin resistance. Reaven et al [22] recently reported that an abnormally high fasting or two-hour post glucose challenge serum insulin levels are the best simple clinical indicators of insulin resistance. However, Reaven holds the position that no test easily used in normal clinical practice at present is really satisfactory for demonstrating the presence of insulin resistance, mainly due to the lack of standardization of serum insulin assays [23].

In view of the close connection between the characteristic risk factors of diabetes and cardiovascular disease, as formalized in the concept of the metabolic syndrome, the hypothesis that diabetes and cardiovascular disease arise from a "common soil" has become attractive, i.e. adult onset diabetes should perhaps be viewed basically as a vascular disease. This point was recently made by Harvard's Frank Hu and Mier Stampfer in an editorial [24] concerning a study by Hunt et al [25] that linked the development of type 2 diabetes and the development and progression of atherosclerosis (as measured by elevated carotid artery intima-media thickness levels). This may well be a turning point in the matter of thinking about and preventing type 2 diabetes, since it emphasizes the need to reduce the risk of atherosclerosis and to treat the risk factors such as hyperlipidemia (elevated cholesterol and triglycerides) and hypertension aggressively, hopefully first with diet and lifestyle changes. A recently reported study on elevated CVD risk prior to the clinical diagnosis of type 2 diabetes also supports the "common soil" hypotheses [26]. In this follow-up study, women who went on to develop type 2 diabetes had a relative risk of 3.75 (3.17 after adjusting for BMI, smoking and other CVD risk factors) for a heart attack and 2.30 for stroke in the period prior to the diabetes diagnosis, as compared to women who did not go on to develop diabetes.

WHY DO PEOPLE BECOME OVERWEIGHT AND OBESE? The answer depends on to whom one listens. Being overweight, incidentally, is generally defined as having a Body Mass Index (BMI) of between 25 and 30, whereas obesity involves a BMI of greater than 30. Thus the healthy range is generally considered to be below 25, although very low numbers, especially if they are decreasing, should prompt an investigation of pathological causes. A low BMI can also be related to smoking which dulls the appetite in some individuals. BMI is calculated by multiplying 703 (unit conversion factor) times weight in pounds and dividing by the square of the height in inches (kg/m2). Today it has largely replaced older "ideal weight" tables both in clinical practice and research.

The conventional explanation for being overweight or obese is that simply not enough exercise or physical and metabolic activity occurs to compensate for the calories consumed, i.e. more calories are consumed than are required to maintain normal weight for a given level of physical activity. For any given level of physical activity, if more calories are consumed than needed, then the excess is stored as fat. Consumption of high levels of rapidly digested carbohydrates can produce high transient levels of insulin, and these high levels of insulin are thought to facilitate the storage of fat from carbohydrates converted into fat. This also fits in well with the theory [27] that the increase in overweight and obesity in the past 20-30 years is due in part to the replacement of dietary fat by sugar and starchy foods.

However, there can be little doubt that the question posed at the beginning of this section is far from simple. Consider the so-called French Paradox. The French do not have the overweight or obesity problem nearly to the extent seen in North Americans. Their incidence of heart disease is dramatically lower (about one-third) than ours. They eat baguettes, greasy croissants, liver pate, butter, cheese, lots of olive oil, etc., i.e. lots of fat. Low- fat or fat-free foods are almost unknown on French grocery store shelves. It is estimated that they get 35-45% of their calories from fat. Their obesity rate is about 8% and constant compared to 30% and growing in North America. One company in the US that specializes in oversized coffins to accommodate the obese reports a 20% annual growth rate in sales (National Post, September 28)! Needless to say, this paradox has attracted considerable attention over a number of years. The French Paradox obviously goes against the thesis that fat makes one fat, which was discussed at in a review in IHN [1] with particular reference to the views and research of Dr. Walter Willett, who regards this notion as a fallacy [28,29]. Foreyt and Poston have recently presented a "symposium consensus " view on this subject [30] which emphasized the role of lifestyle, excessive caloric consumption from all sources, and decreased physical activity as causes of obesity.

A very interesting view of the French Paradox is presented by Dr. Will Clower in the new book The Fat Fallacy [31]. Clower is a neurophysiologist on the faculty of the University of Pittsburgh. He spent two years as a research fellow in Lyon, France and availed himself of the opportunity to study in an informal way the French Paradox. The French have radically different eating habits as compared to North Americans. They eat smaller portions of a greater variety of food. Their meals tend to be, whenever possible, special occasions and extend, whenever time permits, over a much greater period of time than do ours. They take small bites, and rarely stuff their mouths' as do many North Americans. They prepare, eat and enjoy food with almost religious fervor. The idea of heaping plates and a quick, gobble-it-down-and-run meal are foreign to their eating philosophy. The French also have salad after the main meal. When there is vinegar in the dressing, this tends to slow down digestion, as does the cheese that generally follows. Desserts, if offered, are generally small and may well consist of fruit. Their meat consumption is lower than ours and their use of olive oil much greater. Between-meal snacking is uncommon, as is the heavy consumption of the standard fare of what we find in the local doughnut shop or they find in their boulangerie-pâtisserie, and their pastries incidentally tend to be very pricey. The consumption of what Cower calls "faux-foods", e.g. highly processed foods from the super market freezer, canned goods shelves or in the form of ready-to-eat dinners, is much lower. The drinking of wine with meals is almost universal, and starts at a fairly early age. Food is generally prepared with great care and much attention to flavor, taste and presentation. With many cooks, it comes close to being an art form. While there are fast food restaurants in France, they do not represent a significant aspect in French eating habits.

An interesting and popular theory regarding the tendency to become obese or overweight, the "thrifty genotype" hypotheses, holds that many individuals are very efficient at metabolic pathways that lead to the storage of fat during times of feasting, since this would have had a big survival advantage tens of thousands of years ago when humans had to endure long periods of food shortages. We have essentially the same genetic makeup. Today the situation is one of feast rather than famine, every day, at least in North America, and this feast now has large portion sizes, low-fat foods, unknown until very recently, loaded with refined carbs, a fast-food industry making a big play on "super sizing," and all-you-can-eat buffets that are the rage.

Finally there are familial and genetic predispositions to obesity, as well as endocrine causes. The latter include Cushing's syndrome, and some hypothalamic tumors, and as well, hypothyroidism can cause weight gain by reducing the metabolic rate. One would hope that physicians dealing with patients presenting with obesity problems would examine these possibilities.

Thus stability of body weight or weight gain appears to involve a complex set of factors, such as the amount of daily exercise, the amount of food eaten and how it is eaten, the nature and content of meals and snacks, the amount of food that is required to produce satisfaction, the rate of return of hunger and the urge to eat again, and restraint regarding the portions offered or available. Willett's recent book Eat, Drink and be Healthy (Chapter 3) contains an interesting and relevant review of this subject [27].

BEING OVERWEIGHT OR OBESE CARRIES SERIOUS RISKS. The number of Americans that are overweight or obese has rapidly increased in the last two decades from 47% to about 60% of the population. Below are summarized some of the unfavorable health aspects associated with obesity or being overweight.

• The risk of death from all causes increases throughout the range of moderate to severe overweight for both men and women in all age groups. The risk associated with a high BMI is greater for white as compared to black individuals [32]. Many attempts to correlate mortality with BMI show a U shaped curve, but the interpretation of the increased risk at low BMI is subject to much debate, is related to the inclusion of smokers, and is difficult to correct for long term effects of diseases that cause wasting and are ultimately fatal [33]. This also causes a problem when attempts are made to establish guidelines for a "healthy weight" [33].
• Increased body weight is associated with increased death rates from all cancers combined and for cancers at specific sites, in particular esophagus, colon and rectum, liver, gallbladder, pancreas, kidney, non-Hodgkin's lymphoma and multiple myeloma. Significant trends of risk and higher BMI were seen for death from stomach and prostate cancer in men and breast, uterus, cervix and ovary cancer in women [34]. Thus avoidance of weight gain appears to be an important factor in cancer prevention [35].
• Being elderly, female and overweight carries an enhanced risk of Alzheimer's disease, according to a study published in 2003 [36].
• An interesting study just published indicates that abdominal obesity is an independent and potent risk factor for ischemic stroke in all race-ethnic groups, and is a stronger risk factor than BMI. Also a greater effect was observed among younger persons [37].
• It has been theorized that insulin resistance and obesity are involved in a vicious circle, where once obesity occurs, basal lipolysis in the enlarged fat mass causes increased free fatty acid levels which tend to increase insulin resistance and hyperinsulinemia, and the hyperinsulinemia ultimately leads to fat storage and more obesity, and thus the cycle continues [38]. Unless steps are taken early to halt the weight increase and abdominal fat deposition, the patient may be "swept away in the morbidity and mortality of the metabolic syndrome" [38].
• There seems little question that obesity is related to an elevated risk of hypertension, elevated plasma insulin and insulin resistance, adult-onset diabetes, and unfavorable blood lipid profiles, with the end result of increased risk of CVD as well as non-CVD complications associated with diabetes [39]. There is also growing evidence that emerging risk factors—insulin resistance, a proinflammatory state, and a prothrombotic state are common in obese persons and are independent risk factors for the development of atherosclerosis [40].

This is by no means a complete listing of the suspected or documented adverse aspects of being overweight or obese. For example, the adverse effects on joint health have been omitted. Also, space does not permit a detailed discussion of the influence of gender, age, or ethnic origin on the risks of obesity or being overweight, but there are definitely substantial differences observed. When risk factors are examined as a function of BMI, the relationship is frequently an increasing linear relationship, or one that curves upward, with increased risk having a threshold in what is considered the upper limit of the normal range, i.e. about 23-25 kg/m2 [33,34]. Thus adjusting diet to halt weight gain at its onset is easily justified. While with the obese, weight reduction to achieve a BMI in the normal range is in many cases unrealistic, studies consistently indicate substantial declines in risk for many health problems with only a 10 or 15% decrease in BMI, even though the patient is still overweight or obese [33].

The implications are clear. The percentage of the population in North America that is overweight or obese is already very high and is growing at an alarming rate. Thus far the recommendations of The Establishment, followed by large numbers of individuals for several decades, have not resulted in a change in the bleak picture. Americans were told to decrease their fat consumption, which they did (as a percentage of total calories), but they only collectively got fatter [2,27]! This is clearly a crisis situation, and as we will see below, The Establishment is slowly changing its position. But unless dramatic changes occur in actual eating habits among the general public, some of whom have become highly skeptical or cynical regarding flip-flops in Establishment dietary recommendations, the implications as regards the coming impact on the heath care systems, the health care insurance industry, and the taxpayer are almost beyond comprehension. The situation is especially critical because of the impact of the obesity epidemic includes major areas of illness, i.e. cancer, CVD, and diabetes. The name of the game, so to speak, is to avoid or delay the onset of CVD, diabetes and other health problems by not being overweight or obese. Clearly, the related metabolic syndrome is something to avoid like the plague. There is considerable evidence suggesting that diet can play an essential role in avoiding the metabolic syndrome or at least significantly reducing the magnitude of the problems that characterize it, and insulin resistance appears to be reversible if caught early enough [14,9]. Interested readers may also wish to consult the book by Challem et al [41] for more information on reversing insulin resistance.

While this review will not discuss such lifestyle aspects as exercise and stress reduction, these must be very seriously considered along with diet in context of achieving or maintaining health. The role of exercise in both weight control and weight reduction cannot be overemphasized. Recent studies suggest that between 50% and 70% reductions in the incidence of heart disease and diabetes can be achieved by diet and lifestyle alone [4,5,6,7,8]. By normal standards of risk reduction, these numbers are sensational.

DIET AND CANCER IN GENERAL. Clearly an important question when judging diets. It is a difficult area since prospective cohort and case-control studies frequently disagree. This was discussed in the IHN review [1] in connection with cancer and fat. In terms of positive risk factors, large prospective studies have not supported the role of dietary fat. Instead, according to a recent review by Willett [42], positive energy balance, reflected in early age for the onset of menstruation and weight gain as an adult, appear to be the important determinants of the risk of both colon and breast cancer. Likewise, lack of physical activity has been shown to be associated with positive risk for these diseases. Thus diet enters indirectly when it contributes to being overweight or obese. In terms of decreasing risk, the role of fruits and vegetables appears to be overstated [42], but Willett emphasizes the potential role of folic acid in connection with both breast and colon cancer. The effects of folic acid consumption appear strongest among persons who regularly consume alcohol, which itself is associated with a risk of these cancers. A recent study by Terry et al [43] found from a large prospective study that individuals who consumed very low amounts of fruit and vegetables had an enhanced risk of colorectal cancer. The connection between dairy products and prostate cancer appears to be absent, but there is a modest risk associated with a large intake of calcium >2000 mg/day vs. <700 mg/day [44]. Willett's review ends with the following conclusions which are also similar to those given in his book [27]:

• Weight control and regular physical activity should be high priorities for the prevention of cancer.
• Decisions about dietary fat should be made primarily on it relationship with CVD, not cancer. The 2002 review by Moyad [45] takes essentially the same position.
• Consuming an abundance of fruits and vegetables and eating grains in a minimally processed, high fiber form is desirable, but the benefits appear greater for CVD than for cancer.
• Adequate folic acid intake appears important in reducing cancer risk, particularly if alcohol is consumed regularly. Taking a multiple vitamin is the most reliable approach.
• Aside from the above, one must wait for the results of 30 large prospective studies that are underway in order to form additional significant conclusions regarding diet and cancer.

Specific reference will be made in Part II to recent studies that also bear on this subject in the context of either fat and red meat or carbohydrate.

Part II of this review will explore some of the information from scientific studies that relates to fat, carbohydrate and protein consumption, with emphasis on questions of the impact of choices regarding the nature, quantity and quality of these macronutrients on health. Part III will discuss both the so-called fad-diets and the current Establishment diet recommendations, using the information from Part II as a guide.

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