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McKeigue et al. described in 1991 the propensity to abdominal obesity and thicker truncal skinfolds as being greater in South Asians than in British adults, and for each increment in waist/hip ratios, there was a greater increase in glucose intolerance, plasma insulin levels, diabetes, hypertension, and plasma triglyceride levels in the South Asians than in the British Caucasians [32]. These findings mirrored the concerns expressed by clinical researchers such as Misra et al. [33] from India, who highlighted the problem of abdominal obesity and its associated dyslipidemia at low BMIs in Indian slum dwellers. This was also noted by the subsequent WHO Singapore meeting [8] and then led the IOTF to assess whether these propensities to diabetes and hypertension were evident on a population basis by comparing Australasian data with large data sets derived from a series of studies across Asia. Iranian data were included in the reference data set from Australia and New Zealand as they were considered for practical purposes Caucasian. This addition may have been a mistake (see below), but their inclusion did not affect the overall conclusion, based on the analysis of 21 population groups with about 263,000 individuals, that those with abdominal obesity had a greater propensity to diabetes but not to hypertension, and that the Asian community was particularly prone to abdominal obesity and its hazardous consequences [30].

Genetic susceptibility could account for this Asian propensity to abdominal obesity and indeed to excess diabetes and lipid disorders at each increment of waist enlargement, or it could be attributed to other factors. A genetic basis is supported by the relatively new analyses of human evolution that have shown the different patterns of genetics as the human race evolved out of East Africa and then left Africa to evolve through the Middle East into Europe, Asia, and then across the Siberian/Alaskan link (now the Behring straits) into North America and down into Central and South America [34]. The most significant changes are those that involve the much more unstable mitochondrial DNA with its faster rate of mutation than nuclear DNA. There are very clear patterns of mitochondrial change, designated by different haplotypes, with a subset leaving Africa and subsequently evolving down multiple haplotype pathways and with some interbreeding with early hominids, the Neanderthals and Denisovans. There are mutations of mitochondrial DNA that are associated with diabetes, but as yet, there are no extensive population studies of genetics that also test for the prevalence of glucose intolerance and diabetes in populations across the world, as well as associated haplotype analyses.

This seemingly special Asian propensity to abdominal obesity and diabetes was then shown to be a more general feature when analyses of the 2006 national survey of Mexican adults found the same features – both a greater propensity to abdominal obesity and a greater prevalence of diabetes and hypertension at each increment of abdominal expansion [35] as shown in Figure 1.2. Furthermore, US studies showed that when ethnic differences were considered, Japanese Americans, as well as Hispanic Americans, were both more likely to have abdominal obesity and greater rates of diabetes at each increment of abdominal expansion than American Whites [36]. African Americans have higher BMIs than Whites or Hispanics, but their diabetes rates are even higher than one would expect for their greater size. However, attempts to identify a genetic basis for this excess diabetes in Africans have so far been unsuccessful [37], with studies of the African diaspora showing marked differences in glucose metabolism in different communities with different BMIs and degrees of abdominal obesity enhancing glucose intolerance but they were also eating different diets and with objectively measured differences in physical activity [38]. So there was no suggestion that dilution of the African genome in Jamaica and the United States had distinct weight independent effects as their results did not differ from those observed in Ghana and South Africa.

Figure 1.2 The prevalences of obesity in men and women in cohorts with over 263,000 adults either from Asia or from Australasia and Iran (depicted as Caucasians) [30]. Superimposed on this graph are data from the Mexican national survey in 2000 [35]. The Mexican study compared the national survey data with nationally representative data for US non‐Hispanic Whites, but these data are not shown in this graph as they were almost identical to those of the Australasian/Iranian data from the Asian study.

Furthermore, the seemingly genetically obesity‐prone Pima Indians from Mexico and Arizona in the United States show that with similar genetic profiles, there are big national differences in BMI and diabetes prevalences which are largely environmentally determined [39]. Very low obesity and diabetes rates occur in the hard‐working, home‐farming Pima Mexicans consuming a 25% fat, high fiber diet with a negligible sugar content [40]. So it is difficult to be sure what constitutes a greater genetic propensity to diabetes in different ethnic groups and how this relates to abdominal obesity without taking account of their prevailing diet and physical activity [41]. Indeed, the propensity to develop type 2 diabetes has been related to the duration of being overweight/obese, as well as the magnitude of excess weight [42].

The impression that Caucasians are relatively protected from diabetes associated with weight gain was further amplified by our findings in the Middle East. Carefully conducted randomly selected populations in each of the 21 countries covered by the WHO Eastern Mediterranean Region (EMR), i.e. including not only the Gulf countries, Lebanon, Syria, and the North African countries abutting the Mediterranean but also Djibouti, Somalia, Sudan, Afghanistan, and Pakistan showed (Fig. 1.3) that, despite the wide‐ranging levels of average BMI in both men and women, the national average diabetes rates are appreciably higher in the EMR than in the 28 countries of the Europe Union throughout the range of average BMIs.

Figure 1.3 The relationship between the prevalences of obesity and diabetes in each of the 21 WHO Eastern Mediterranean countries compared with equivalent data from the 28 countries of the European Union. Diabetes prevalence rates are about twice as high in the Eastern Mediterranean countries as in the European Union at equivalent obesity rates. These data are based on randomly selected adults with measured anthropometry and fasting blood glucose levels in each country undertaken according to a standard protocol (the WHO STEPS program).

(Source: Reproduced from Alwan et al. [43].)

If these differences are not genetic, then what might be the basis for the increased susceptibility to abdominal obesity and diabetes? Barker et al. [44], in his original study, claimed that lower birth weight in babies of pre‐Second World War women in England seemed to determine an increased propensity of the offspring to develop the metabolic syndrome and diabetes 64 years later. The conditions amongst the working class in England at that time had already been documented as nutritionally totally inadequate [45], so Barker ascribes the propensity to metabolic syndrome and diabetes as reflecting the impact of maternal malnutrition with induced poor fetal growth. Yajnik in Pune, India, then showed with Barker startling differences between the offspring of mothers in Pune and those of now well‐fed mothers in Southampton, England [46]. The Indian children were smaller, with less lean tissue, and relatively fatter with distortions of the organ sizes which already related to increased insulin resistance in the newborn Indian babies. This seemed to be proportional to the degree of vitamin B12 deficiency and the discordant folate/B₁₂ nutritional status of the mother [47], which has been shown to influence fetal growth. These vegetarian women were often being given inappropriately high doses of folic acid without any B12 and most likely would have been eating very modest amounts of food providing nucleic acids. Thus the generation of nucleotides in the crucial phase of early fetal development would have been compromised due to the lack of vitamin B12 required to generate methyl groups through folate remethylation.

These early nutritional effects relating to organ metabolism are probably amplified if there is some subsequent childhood malnutrition, because although they can recover their intestinal absorptive capacity on refeeding, their ability to mobilize insulin after a standard glucose test remains markedly reduced despite being extremely well‐fed for months and with body weights that had returned to the normal weight for their heights [48]. Further analyses have shown that this effect is long‐standing because adults in Jamaica who had been malnourished as children had a persisting impairment of insulin secretion [49], and this defect was also seen in survivors of early fetal deprivation during the Dutch famine [50].

The Millennium report for the United Nations on the global prevalence of persisting childhood malnutrition [51] highlighted the fact that almost all non‐Western countries after the Second World War had high prevalences of childhood malnutrition leading to long‐standing global, intergenerational malnutrition, which persisted throughout life. So a lifespan approach [52] to considering the problem of adult obesity begins with the nutritional state of the mothers before and during pregnancy with all its pathological and epigenetic implications for the offspring. We already know that the increase in body weight in previously malnourished women as they enter pregnancy leads to a much greater propensity to gestational diabetes [53], and they are then more likely to develop diabetes later themselves as well as having bigger and fatter children.

These global states of malnutrition almost certainly have lasted for millennia, so the early descriptions of obesity associated with ill health described by Bray are in line with the observed debilitating disease such as diabetes resulting from the impact of excess weight gain in people with lifelong malnutrition. In contrast, the Roman description of relatively healthy obese may then have reflected the better overall nutrition of the Romans in their Mediterranean environment.