Copyright © 2008 by The Endocrine Society
Obesity and the Metabolic Syndrome in Developing CountriesAnoop Misra and Lokesh KhuranaCenter for Diabetes, Obesity, and Cholesterol Disorders (A.M., L.K.), Diabetes Foundation (India), New Delhi 110016, India; and Department of Diabetes and Metabolic Diseases (A.M.), Fortis Hospital, New Delhi 110070 Address all correspondence and requests for reprints to: Anoop Misra, Director and Head, Department of Diabetes and Metabolic Diseases, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi 110070, India. E-mail: anoopmisra{at}metabolicresearchindia.com.
Context: Prevalence of obesity and the metabolic syndrome is rapidly increasing in developing countries, leading to increased morbidity and mortality due to type 2 diabetes mellitus (T2DM) and cardiovascular disease. Evidence Acquisition: Literature search was carried out using the terms obesity, insulin resistance, the metabolic syndrome, diabetes, dyslipidemia, nutrition, physical activity, and developing countries, from PubMed from 1966 to June 2008 and from web sites and published documents of the World Health Organization and Food and Agricultural Organization. Evidence Synthesis: With improvement in economic situation in developing countries, increasing prevalence of obesity and the metabolic syndrome is seen in adults and particularly in children. The main causes are increasing urbanization, nutrition transition, and reduced physical activity. Furthermore, aggressive community nutrition intervention programs for undernourished children may increase obesity. Some evidence suggests that widely prevalent perinatal undernutrition and childhood catch-up obesity may play a role in adult-onset metabolic syndrome and T2DM. The economic cost of obesity and related diseases in developing countries, having meager health budgets is enormous. Conclusions: To prevent increasing morbidity and mortality due to obesity-related T2DM and cardiovascular disease in developing countries, there is an urgent need to initiate large-scale community intervention programs focusing on increased physical activity and healthier food options, particularly for children. International health agencies and respective government should intensively focus on primordial and primary prevention programs for obesity and the metabolic syndrome in developing countries.
Nutritional, demographic, epidemiological, and socioeconomic transitions are occurring in many developing countries. Continuing undernutrition and escalating over nutrition has created double jeopardy of communicable and noncommunicable diseases (NCDs) (1, 2). This double burden poses apparently insurmountable health and economic challenges in resource-constrained populations. Obesity is a natural consequence of over nutrition and sedentary lifestyle. Persistent obesity dysregulates metabolic processes including action of insulin on glucose-lipid-free fatty acid metabolism and severely affects processes controlling blood glucose, blood pressure, and lipids. Thus begins a cluster of conditions; dysglycemia, dyslipidemia, hypertension, and procoagulant state, known as the metabolic syndrome (3). Data suggest that the obesity and the metabolic syndrome are immediate precursors of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) (4, 5, 6, 7). Increasing burden of obesity, the metabolic syndrome, T2DM, and CVD in developing countries has created an urgent need to strategize health policies and mass intervention programs to tackle nutrition and continue efforts to manage undernutrition. Clearly these efforts require a thorough understanding of factors influencing and driving obesity and the metabolic syndrome in developing countries. In this review, we shall discuss the epidemiology of obesity and the metabolic syndrome, lifestyle and nutritional transitions, determinants, social and economic impacts, and possible solutions for prevention of obesity and the metabolic syndrome in developing countries. Developing countries have been categorized as per the International Monetary Funds World Economic Outlook Report, April 2008 (8). The literature search has been carried out using the terms, obesity, insulin resistance, the metabolic syndrome, diabetes, dyslipidemia, nutrition, physical activity, and developing countries, in the medical search database PubMed (National Library of Medicine, Bethesda, MD) from 1966 to June 2008. A manual search of the relevant quoted references was also carried out from the retrieved articles. Data have also been taken from nutritional surveys in different developing countries and web sites and published documents of the World Health Organization (WHO) and Food and Agricultural Organization (FAO). It is important to note that, despite elaborate literature search, data regarding obesity and the metabolic syndrome are not available from many developing countries.
With a substantially high annual rate of increase of obesity and rapid emergence of the metabolic syndrome in most developing countries, the shift in the pattern of NCDs is occurring at a faster rate than it did in the industrialized regions of the world half a century ago (9). Global prevalence of chronic diseases is projected to increase substantially over the next 2 decades in developing countries. Indeed, 60% of the global burden of chronic diseases is expected to occur in developing countries (10). CVD is already the leading cause of mortality in many developing countries (11). In the World Health Report (1999), it was stated that in 1998, 78% of the burden of NCDs and 85% of the CVD arose from the developing low- and middle-income countries (12). Furthermore, according to projected data, chronic diseases will account for almost three quarters of all deaths worldwide by 2020 and that 71% of deaths due to CVD and 70% of deaths due to diabetes will occur in developing countries (13). In fact, there are more patients with CVD in India and China than in all the economically developed countries (14). Globally, by 2000, 171 million patients with diabetes are projected, which is expected to increase to 366 million in 2030, of which 298 million will be in developing countries (15). The number of people with diabetes is projected to double (during 2000–2030), in three of the six developing regions, including, the Middle East and North Africa, South Asia, and sub-Saharan Africa (15). India has and will continue to have the highest number of patients with diabetes in the world (16). The resulting increase in morbidity and mortality due to obesity and consequent chronic NCDs is a matter of great concern. Between 1990 and 2020, mortality from CVD in developing countries is expected to increase by 120% for women and 137% for men (17), which is expected to be substantially greater than from developed countries (29 and 48%, respectively) (18). A near tripling of CVD mortality in Latin America, the Middle East, and sub-Saharan Africa is expected to occur in next 2 decades (19). In India, increase in CVD mortality is expected to reach 2 million by 2010 (20).
Obesity (Table 1 According to the WHO estimates, the undernourished population in the world has declined and is roughly around 1.2 billion, whereas the overnourished population has increased to 1.2 billion (21). WHO data also show that, globally, there are more than 1 billion adults overweight and 300 million obese people. The problem of obesity is increasing in the developing world with more than 115 million people suffering from obesity-related problems (22). In 1998, Popkin and Doak (23) reported an increase in prevalence of obesity from 2.3 to 19.6% over the last 10-yr period in several developing countries. Obesity rates have increased 3-fold or more since 1980 in Middle East, the Pacific Islands, Australasia, and China (24).
Whereas the prevalence of obesity may not be high in many areas in some developing countries, like China, Japan, and certain African nations, it is extremely high (>75%) in other countries like urban Samoa. Even in low-prevalence countries, the prevalence is significantly high (>20%) in urban areas (23). Recently application of lower cutoff of body mass index (BMI) (Asian criteria of overweight: 23–25 kg/m2 and obesity: 25 kg/m2) (25) has led to increase in prevalence figures in several Asian countries (26, 27). Overall, it appears that overweight and obesity may already be more than underweight and undernutrition in many developing nations. Rural-urban differences in obesity, the metabolic syndrome, and T2DM is seen in most developing countries (28). Furthermore, whereas overweight and obesity in underprivileged people in developed countries is substantial, in developing countries rural-based people are mostly lean and have low prevalence of T2DM and CVD. However, underprivileged people residing in urban areas (mostly rural to urban migrants) show increasing prevalence of overweight/obesity and other cardiovascular risk factors (29). Abdominal obesity is an important risk factor for T2DM, the metabolic syndrome, and CVD (30, 31, 32) and is particularly prevalent in certain ethnic groups of developing countries (e.g. South Asians, Hispanics, etc.). In the International Day for Evaluation of Abdominal obesity study (33), waist circumference data from 63 countries showed highest prevalence of abdominal obesity in South Asians compared with north Europeans and other Asian ethnic groups. Of note, 30.9% of men and 32.8% of women in industrial population in India were reported to have abdominal obesity (34). Using Asian cutoffs of waist circumference, 25.7% women and 33.1% men in urban South Korea had abdominal obesity (35). Data from countries in sub-Saharan Africa, South America, and the Middle East also showed similar high prevalence of abdominal obesity: 67% of women and 18% of men in urban Cameroon (36), 43% in Venezuela (37), and 24.6% in Oman (38). Higher prevalence of obesity and abdominal obesity has been seen in women compared with men in many developing countries, consistent with the sedentary lifestyle as discussed later. For example, the prevalence of obesity (standardized for age) in adults in Seychelles was 5-fold more in women compared with men (20.9 vs. 4.2%, respectively) (39). Furthermore, in this population, the prevalence of obesity in women increased from 8.9% at age 25–34 yr to 29.4% at age 35–44 yr and reached a plateau thereafter, whereas the prevalence did not change with age in men. Correspondingly, prevalence of T2DM (standardized for age) was also higher in women (women, 4.6% vs. men, 3.4%) (39). The age-standardized prevalence of overweight (BMI > 25.0 kg/m2) was higher in women (31.1%) than men (26.9%) in China (40). Other developing countries show similar trends regarding higher prevalence of obesity in women: Iran (men, 24% and women, 42%), (41) and Sri Lanka (men, 20.3% and women, 36.5%) (42).
Obesity in children (Table 2 Similar to adults, the prevalence of overweight and obesity and overweight in children in developing countries shows an increasing trend. This is a serious challenge because malnutrition and stunted growth are often seen to coexist in children, and eliminating undernutrition without increase in obesity is required (43). Since 1986, several surveys in preschool children show increasing obesity in most countries in Latin America and the Caribbean, along with the Middle East and North Africa, which is comparable with prevalence rates of childhood obesity seen in the United States (43). Similar trends have also been observed in India, Mexico, Nigeria, and Tunisia over the past 2 decades (44). The prevalence of obesity in 5- to 12-yr-old children in Thailand increased from 12.2 to 15.6% over a period of 2 yr (24). Increase in the prevalence of overweight among older children and adolescents has been seen as well; from 4.1 to 13.9% between 1975 and 1997 in Brazil, from 6.4 to 7.7% between 1991 and 1997 in China, and from 16 to 24% between 2002 to 2007 in New Delhi, India (45, 46). Furthermore, overweight was more common in urban areas vs. rural areas, privately funded schools vs. government funded schools (46), girls vs. boys (46), and children born to more educated mothers in India (43).
Adults In line with the rising prevalence of obesity, the metabolic syndrome is also increasing in developing countries. High prevalence of the metabolic syndrome has been reported from sub-Saharan Africa and Middle East countries; South Africa, Morocco, Oman, Turkey, and Iran showed prevalence of 33.5, 16.3, 21, 33.4, and 33.7%, respectively. The prevalence rates are also high in Venezuela (31.2%) and urban Brazil (25.4%) (37, 47). The situation appears to be similar in South Asian countries. The prevalence of insulin resistance as measured by surrogate markers in Asian Indians residing in India ranged from 20 to 55%; the variation in the prevalence was due to heterogeneity of the population (higher in urban vs. rural) and socioeconomic strata (SES) (higher in the people belonging to high SES vs. low SES) (48, 49). The recent data show that one fourth to one third of urban population of India has the metabolic syndrome (50). Furthermore, the prevalence is 1.5–2 times higher in women compared with men (34, 50). Interestingly, certain communities in India (e.g. Punjabi Bhatia community in north India) have inordinately high tendency to have obesity, T2DM, and the metabolic syndrome (51). Prevalence of the metabolic syndrome in population of Sri Lanka is strikingly high as well; 35% in males and 51% in females (n = 16,729) (Wijesuriya M., personal communication). In the Sindh province of Pakistan, overall prevalence of the metabolic syndrome was 34.8 and 49% according to International Diabetes Federation (IDF) and modified National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) definitions, respectively (n = 363) (Basit A., personal communication). There is a paucity of data on prevalence of insulin resistance and the metabolic syndrome from other south Asian countries: Bangladesh and Nepal.
Prevalence of the metabolic syndrome is rapidly increasing in East Asia and China. Using modified NCEP, ATP III criteria, prevalence was 29.0 and 16.8% in South Korean men and women, respectively (35). A study done in Singapore not only highlighted change in prevalence when criteria for abdominal obesity were modified but also showed ethnic differences. Tan et al. (52) showed that the prevalence was highest in Asian Indians (28.8%), followed by the Malays (24.2%) and then the Chinese (14.8%), and ethnic differences persisted in both genders (52). Age-standardized prevalence of the metabolic syndrome in China was reported to be 9.8% in men and 17.8% in women and was higher in urban than in rural populations (40). High prevalence of the metabolic syndrome (22.9%) among adults in city of Shanghai, China has been reported, even after adjustment by age and gender (15.3%) (53). Hong Kong Chinese showed high prevalence of several cardiovascular risk factors comprising the metabolic syndrome: 30%, central obesity; 34%, low levels of high-density lipoprotein cholesterol (HDL-C); 20%, hypertriglyceridemia, and 47%, hypertension (54). In many of these studies, higher prevalence rates of the metabolic syndrome in women were reported, similar to the gender differences seen in the prevalence of obesity. Children
Data pertaining to the metabolic syndrome in children and adolescents are scarce. This is partly because of lack of consensus on the definition of the metabolic syndrome in children, which is presently defined using different criteria and cutoff points. The recent IDF definition of the metabolic syndrome in children includes waist circumference as mandatory criterion and 2 or more other risk variables (55). The new IDF definition is age specific, taking into account developmental challenges in growing children and adolescents. (Table 4
Phenotype of obesity in several ethnic groups in developing countries appears to be different from that seen in white Caucasians in developed countries. Several investigators have shown that body fat is higher in Asians, particularly south Asians, compared with white Caucasians for the similar level of BMI (27, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72). This body composition feature has been documented in Indonesians, Singaporean Chinese, and Malays. For example, at any given percentage of body fat, BMI value of Chinese, Malays, and Asian Indians in Singapore was 3 kg/m2 lower than that in white Caucasians (73). Furthermore, Indonesians had about a 2 kg/m2 lower BMI but 3% higher body fat than Dutch Caucasians, suggesting cutoff points for obesity in Indonesians should be 27 kg/m2 instead of 30 kg/m2 (74). High percentage of body fat with low BMI value could be partly explained by body build (trunk to leg length ratio and slender body frame), muscularity, adaptation to chronic calorie deprivation, and ethnicity (75). Importantly, obesity-related morbidities (diabetes, hypertension, dyslipidemia) occur more frequently at lower BMI levels in Asians than white Caucasians. In Hong Kong Chinese men, the optimal BMI cutoff to predict diabetes, hypertension, and dyslipidemia was lower than currently recommended (76). Our data on Asian Indians residing in New Delhi, India, showed that about 66% of men and 88% of women, classified as nonobese based on international cutoff of BMI, had one or more cardiovascular risk factor(s). Furthermore, significantly higher odds ratios for hypertension, T2DM, and hypertriglyceridemia were observed in nonobese subjects having upper quartile of percentage body fat compared with the lowermost quartile (77). Based on these data and those by other investigators, it has been suggested that BMI limits for overweight should be lower for Asian Indians (78, 79, 80). Finally, a metaanalysis of data of 13 population-based studies including 239,972 adults in China and Taiwan showed that BMI of 24 kg/m2 had the best sensitivity and specificity for identification of cardiovascular risk factors, and this new limit would prevent about 50% clustering of risk factors (81). Overall, the results of the studies suggest lowering the BMI limits by about 1–3 kg/m2 for the diagnosis of overweight for the Asian populations (82). Although the average value of waist circumference in South Asians is lower than other ethnic groups, abdominal adiposity is significantly more than white Caucasians (65, 83, 84, 85, 86, 87, 88). Raji et al. (89) showed that at similar value of BMI, migrant Asian Indians had significantly greater total abdominal fat and intraabdominal fat than white Caucasians in the United States. In addition, despite lower BMI and waist circumference, Asian Indians had significantly lower glucose disposal rates during the hyperinsulinemic euglycemic clamp, higher procoagulant tendency, and dyslipidemia compared with white Caucasians (85, 89). Furthermore, we reported significantly high odds ratios for hypertriglyceridemia and hypertension in the normal range of waist circumference (70–80 cm) in Asian Indians residing in India (90). The cutoff points of waist circumference in urban Asian Indians living in India based on receiver operating characteristics curve analysis (using T2DM as a reference) for various morbidities were 90 and 80 cm for men and women, respectively (91, 92). Similarly, lower waist circumference cutoff points than presently accepted have been reported based on the morbidity data for several non-Asian populations of developing countries, including Nigeria, Cameroon, Jamaica, St. Lucia, Barbados (93), Brazil (94), Mexico (95), and Iran (96). It is important to note that South Asians have thick sc adipose tissue as highlighted by the investigators who used skinfold measurements in their investigations (65, 84, 85, 86, 87, 88). Higher magnitude of insulin resistance in a BMI- and body fat-matched Asian Indian men than white Caucasians in the United States could be explained by thicker truncal skinfolds in the former (85, 97). A significant association of truncal skinfold thickness (signifying high truncal sc adipose tissue) with fasting hyperinsulinemia in Asian Indian children and adolescents has been reported by us (98). Interestingly, thicker subscapular sc fat in Asian Indians has been recorded at birth and is associated with higher insulin levels when compared with British neonates (68). Finally, histological studies of sc adipose tissue showed that Asian Indians have larger adipocytes (reported to be more resistant to the action of insulin) compared with white Caucasians in the United States (3491 vs. 1648 µm2; P = 0.0001) (97). The clinical implication of the latter finding remains to be investigated. Fat accumulation in other tissues in which it is not usually deposited (ectopic fat) has the potential to affect insulin sensitivity. Deposition of fat in liver (nonalcoholic fatty liver disease) and muscle [intramyocellular triglycerides (IMCL)] has been shown to correlate with insulin resistance in white Caucasians (99). It is important to note that Asian Indians have higher hepatic triglycerides levels, which are associated with higher insulin and lower adiponectin levels than white Caucasians (100). We recently reported early abnormalities in hepatic gluconeogenesis pathway in nondiabetic obese and nonobese Asian Indians with nonalcoholic fatty liver disease using in vivo (31) phosphorus magnetic resonance spectroscopy of liver, signifying that glucose metabolism is dysregulated early in Asian Indians with fatty liver, even when they are nonobese (101). We have also shown excess IMCL deposition in soleus muscle in Asian Indians with abdominal obesity; however, unlike white Caucasians, IMCL did not correlate with fasting insulin levels (102, 103). Finally, presence of excess dorsocervical fat (mild buffalo hump) and excess fat deposition under the chin (double chin) may also signify heightened risk for the metabolic syndrome in urban Asian Indians and may be used as phenotypic markers (104). Overall, Asians and South Asians could be classified as metabolically obese (105), i.e. they have several metabolic derangements but are nonobese by conventional BMI standards. These nonobese people usually have high body fat; abdominal adiposity; ectopic fat deposition; and, specifically in South Asians, thick truncal sc fat. These body composition characteristics, individually or in combination, contribute to insulin resistance, dyslipidemia, hyperglycemia, and excess procoagulant factors seen commonly in South Asians (1, 30, 65, 71, 85, 86, 89, 106).
These data have prompted a debate that BMI cutoffs for diagnosis of overweight and obesity should be lower for Asian populations as opposed to currently prevalent international guidelines (70, 107, 108). In a consultation on obesity in Asia and Pacific regions, lower cutoffs for diagnosis of overweight and obesity were suggested; 23 kg/m2 or greater and 25 kg/m2 or greater, respectively (25). More recently a WHO expert consultation agreed that Asian populations have different associations between BMI, percentage of body fat, and health risks than do European populations. The experts also opined that the proportion of Asian people with a high risk of T2DM and CVD is considerable at BMI values lower than the existing WHO cutoff point for overweight (
Some ethnic-specific guidelines are available for the definitions of the metabolic syndrome. With new data on cutoffs of waist circumference from Asian populations, the IDF and NCEP, ATP III have introduced modified definitions, which specify ethnic-specific criteria for waist circumference. However, whether predictive value of these definitions for T2DM and CVD is better than previous definitions of the metabolic syndrome for ethnic groups in developing countries has been debated (82). Furthermore, taking in cognizence of distinctive body composition of Asians, and in particular South Asians, new definitions of the metabolic syndrome, including specific body composition characteristics (e.g. truncal sc fat measured by subscapular skinfold thickness), have also been proposed (113). Given some recent evidence that the metabolic syndrome and its components are associated with T2DM but have weak or no association with vascular risk in elderly populations (21), predictive value of any definition of the metabolic syndrome for CVD needs to be investigated further in different ethnic groups in the developing countries. The varying relationships of the components of the metabolic syndrome with CVD risk in different ethnic groups mostly in developing countries necessitates further studies, as discussed below. Detailed discussion on ethnicity and the metabolic syndrome is beyond the scope of this review and can be referred to in our major published review (114). The first concern with the applicability of the metabolic syndrome criteria to different ethnic groups in developing countries is that the risk imparted by the cutoffs for the criteria (other than waist circumference, discussed above) that comprise it varies according to ethnicity. Data suggest that the hypertension criterion does not accurately indicate CVD risk across populations due to differences in the way hypertension imparts CVD risk across ethnic groups. It is generally accepted that hypertension has the weakest association with insulin resistance among all factors that comprise the metabolic syndrome (115). Interestingly, the Chinese population has a lower prevalence of hypertension than North American Caucasian cohort, but the CVD risk associated with increases in blood pressure is proportionally greater in the Chinese (116). Similarly, Filipino females with a higher prevalence of both hypertension and the metabolic syndrome than white Caucasians did not show excess subclinical atherosclerosis (117). Several studies in the United Kingdom have shown higher prevalence rates of hypertension in populations of African ancestry but lower rates of mortality due to CVD when compared with white Caucasians and South Asians with hypertension (118, 119). Clearly, mismatches between hypertension and CVD risk is evident in several ethnic groups, indicating that the hypertension criteria of the metabolic syndrome should be altered by either changing the cutoffs for different populations or weighting the individual criteria based on their risk contribution to CVD in each population. One could also debate on deletion of hypertension from the criteria of the metabolic syndrome in ethnic groups in which the relationship between hypertension and CVD risk is weak. Other criteria of metabolic syndrome [serum triglycerides and HDL-C] should be considered on the similar mode. It has been shown that the NCEP, ATP III criterion, which is most likely to identify insulin resistance in individuals, is the triglycerides to HDL-C ratio (120). It is also known that these factors capture much of the cardiovascular risk associated with the metabolic syndrome. Yet Sone et al. (121) noted that in a Japanese population, HDL-C levels were not a significant risk factor for CVD, in contrast to the United Kingdom Prospective Diabetes Study in which HDL-C levels were significantly associated with CVD risk in a British white Caucasian population. Hispanics are known to exhibit higher serum triglyceride and lower HDL-C levels than non-Hispanic Caucasians, (122) yet have similar rates of CVD to non-Hispanic Caucasians (123, 124). An oft-repeated question is whether blood glucose characterizes cardiovascular risk adequately in different populations. In multiracial population in Singapore, Ma et al. (125) noted that mortality risk for T2DM in Asian Indians was higher when compared with Chinese and Malays, yet Chinese and Malays had a higher prevalence of impaired glucose tolerance and impaired fasting glucose (IFG) compared with Asian Indians, suggesting that the progression to T2DM is faster in Asian Indians compared with other Asian ethnic groups. These observations have implications for the relative importance of IFG for CVD risk in different ethnic groups, implying that IFG carries a greater risk for CVD mortality in Asian Indians than other ethnic groups. More accurate standards are needed to weight the risk for elevated blood glucose levels for T2DM and CVD in different ethnic groups in developing countries and alter the cutoffs accordingly, as has been done based on the data from white Caucasian populations (114).
Similarly, differences in the clustering of metabolic parameters have been shown in different ethnic groups in developing countries. The variable clustering of the different components in the metabolic syndrome in different populations suggest varying risk clusters associated with the metabolic syndrome. For example, obesity in African-Americans is more commonly associated with hypertension, whereas obesity-related T2DM is more common in Hispanics (126). Malay females in Mauritius exhibited a relatively high prevalence of hypertension associated with insulin resistance than other ethnic cohorts (127). Thus, there may be combinations of the criteria of the metabolic syndrome that are more appropriate for one ethnic group than another in predicting risk of T2DM and CVD. The evidence we currently have suggests that not only should the cutoffs and weights of the criteria for the metabolic syndrome be altered for different ethnic group in developing countries, but the combinations of the metabolic syndrome criteria for each ethnic group should also be varied. Cumulatively, these data suggest that we need receiver operating characteristics curve analysis-based cutoffs and/or a weighting system for combination of the various criteria of the metabolic syndrome in certain ethnic populations to more accurately capture the risk of T2DM and CVD. Some suggestions for ethnic-specific alterations to define the criteria of the metabolic syndrome are given in Table 5
Finally, in view of the high and increasing prevalence of obesity and T2DM in children and adolescents, there is an urgent need to establish internationally acceptable criteria for the metabolic syndrome. It needs to be researched further whether any ethnic-specific cutoffs of anthropometry or other parameters need to be included while proposing a universal definition of the metabolic syndrome in children, similar to the recent IDF definition of the metabolic syndrome in adults (81). In the recently proposed IDF definition of the metabolic syndrome in children (10–16 y), no ethnic differences in various criteria has been properly accounted for and adequately researched. Furthermore, because many criteria of the metabolic syndrome in adults may not be dysregulated (e.g. blood glucose), additional criteria that occur early in phenotype (e.g. acanthosis nigricans, truncal skinfolds, buffalo hump, and fasting insulin levels) (46, 61, 98, 104) should be considered in the definition of the metabolic syndrome in children. Clinical utility and advantages over any proposed definition of the metabolic syndrome, whether in adults or children, remains to be researched (55). The resolution of this dilemma would greatly impact the preventive and management strategies in tackling the metabolic syndrome and will have important therapeutic implications.
Transitions
Emergence of obesity and the metabolic syndrome in developing countries is due to a number of factors; the most important are discussed below. Demographic transition (shift to low fertility, low mortality, and higher life expectancy) and epidemiologic transition (from widely prevalent infectious diseases to a pattern of high prevalence of chronic lifestyle-related NCDs) have occurred in developing countries as they become economically more resourceful (socioeconomic transition, shift of people from low SES to high SES), causing significant shifts in dietary and physical activity patterns (nutrition and lifestyle transitions, and stress) (Fig. 2
Each type of transition has an important bearing on occurrence of obesity and metabolic risk factors; however, urbanization, nutrition transition, and increasing affluence remain the most important determinants of such dysmetabolic phenotype (Fig. 3
Rapid urbanization (Table 6 Urbanization is the prime driver for nutrition transition and emergence of obesity, the metabolic syndrome and other NCDs in developing countries. Remarkably, in 1999, when the world population was nearly 6 billion, a minimal increase in the populations of developed countries (1.9 to 1.21 billion) was seen compared with those of developing countries (4.87 to 6.9 billion), (128), which were increasingly becoming urbanized. Urbanization is variable within developing regions: almost three fourths of the population in Latin America and the Caribbean, whereas 38% in Africa and Asia are urbanized (129). The latter two regions are projected to have almost 50% urbanization by 2020. Specifically, marked increase in urbanization is projected to occur in India, China, Bangladesh, Nigeria, and Tanzania over the next 2 decades (7, 17, 13, 14, and 17%, respectively) (129). The rural-to-urban migration in many of the developing countries exposes migrants to urbanized diets and lifestyle. Studies done in Brazil and India have clearly shown that many of these migrants, now living in urban slums and city shantytowns, have become obese and also manifest a number of other cardiovascular risk factors (29, 130).
Nutrition transition
Five patterns of nutrition transition, derived from historical references of human development, are present and evolve from one category to another in many ethnic groups and disparate geographical locations in developing countries. Pattern 1 nutrition transition is characteristic of hunter-gatherer populations and comprises diets rich in carbohydrates and fiber and low in fat, especially saturated fat, with a high-activity profile and lean body phenotype. In pattern 2, individuals exist in famine-like situation (low calorie, low protein and fat diets) and have growth retardation and low body fat and fat-free mass. In pattern 3, famine vanes, and nutrition improves, with increase in the consumption of fruits, vegetables, and animal proteins, and this pattern is associated with increasing inactivity. Pattern 4 is now most prevalent in developing countries, conducive to development of obesity, the metabolic syndrome, T2DM, and CVD. With improvement in economy, people become affluent and consume diets high in saturated fats, cholesterol, and refined carbohydrates and low in polyunsaturated fatty acids and fiber, associated with markedly sedentary lifestyle and increased stress. In the last (pattern 5), as people suffering from T2DM and CVD increase in the population, awareness of benefits of balanced diets and regular physical activity increases. Consequently, people attempt to change dietary and physical activity profiles to prevent or delay diseases. This pattern, unlike previous patterns, is driven by an individuals desire to seek healthy behavior, hence may not be evident in large segments of populations, and is likely to be adapted initially by affluent people. Furthermore, impetus to such lifestyle changes may be provided by governments policies, legal actions, and peer practices and hence may vary widely within each country. A rather rapid shift from pattern 3 to 4 in the developing countries is clearly responsible for steep increase in obesity and the metabolic syndrome. As gross domestic product (GDP) of the country increases with improved economy, underweight children decrease, whereas overweight increases predominantly due to nutrition transition (Fig. 3
Most developing countries in Asia, Latin America, Northern Africa, the Middle East, and the urban areas of sub-Saharan Africa have been experiencing a shift in the dietary patterns over the last few decades. Major dietary changes include a large increase in the consumption of fats, particularly animal fat and added sugar and decrease in cereal and fiber intake. Marked increase in the consumption of egg, poultry, pork, mutton, beef, and milk amounting to 1300 kcal/d has been reported in Chinese adults, proportional to increase in the income in China (131). In India and South Asia, high intake of dairy products, sugar, and hydrogenated vegetable oils (e.g. Vanaspati) is widely prevalent (132). Availability of edible vegetable oils for consumption has nearly tripled throughout the developing world (Fig. 4
Importantly, consumption of nontraditional fast foods is occurring at a rapid pace in urban areas of several large cities in South Asia (49). In 1998 U.S.-based transnational food companies (TFCs) invested $5.7 billion (US) in establishing outlets overseas, including many in developing countries (134). Rapid rise in fast food chains in developing countries is exemplified by the spread of McDonalds outlets globally and in Asia (from 951 outlets in 1987 to 7135 in 2002). Foreign direct investment from U.S.-based supermarket chains is increasing in developing and transition markets, notably in Latin America, Asia, and central and eastern Europe (135). In China, fast food chains increased from three in 1987 to 184 in 1997 and 546 in 2002 (136). In this context, Mexico makes an interesting case study. Between 1995 and 2003, sales of processed foods expanded by 5–10% per year. Recent sales has been particularly rapid for snacks (12% rise from January to June 2004), baked goods (55.4% rise from 2000 to 2003), and dairy products (48.1% rise from 2000 to 2003) (137, 138). Furthermore, calories from carbonated beverages increased from 44 to 61 kcal per capita per day between 1992 and 2000 (139). Lastly, locally made fast foods sold by street vendors in several developing countries, particularly in India and China, are equally unhealthy (140). These food items contain high amounts of trans-fatty acids due to deep frying in cheap and widely available hydrogenated vegetable oils. Nutritional intervention programs for undernourished children in developing countries and obesity A particularly interesting issue related to increase in childhood obesity is free meal or feeding programs to control undernutrition in developing countries, which may actually lead to increase in adiposity among those with marginal undernutrition (141). In school feeding programs in Chile, nutritional excess was seen with rapid growth and high prevalence of obesity, with 56% of children under the age of 6 yr and 11.1–14.3% of children in first grade reported to be obese (142). FAO data from 19 Latin American countries show that more than 20% of the population in developing countries received some level of food assistance from nutrition-related programs, whereas prevalence of malnourishment was only 12% (141). It is likely that the scenario is similar in India where free midday meals are provided to schoolchildren who belong to low SES and are studying in government-funded schools. Thus, nutrition programs have evolved beyond the immediate needs of the malnourished and have the potential to increase obesity epidemic in developing countries. Hence, careful selection of beneficiaries of food assistance programs and determination of the right combination of nutrients/foods, education, and lifestyle intervention is required to optimize nutrition and prevent obesity. Such ongoing programs in other countries to overcome malnutrition should be constantly monitored, reviewed, and revised if needed (141). Thrifty genotype/phenotype and maternal-fetal factors It is postulated that thrifty genotype is propagated by survival during famines and lends heightened tendency to develop obesity and T2DM seen in certain ethnic groups in developing countries with abundant food availability. This concept, although interesting, remains hypothetical and lacks firm evidence in the absence of definite identification of such thrifty genes (143). Furthermore, natural selection by famine and tendency of individuals to gain weight with availability of abundant food should apply to the entire human population and should not be restricted to some subpopulations of developing countries (143, 144). Moreover, different prevalence in obesity rates between genders and even between rural and urban-based populations belonging to low SES indicate significant role of environmental and behavioral factors. Interestingly, in rural Gambia, children born low birth weight remained lean and largely free of metabolic diseases when they grew up as adults if they stayed in a rural setting and followed a frugal and traditional lifestyle (145, 146). These data show relative roles of genetic and environmental/behavioral factors, suggesting that behavioral choices appear to be key mediators of development of obesity (147). A thrifty phenotype hypothesis that emphasizes fetal undernutrition leading to altered metabolic programing is perhaps a better explanation in resource-poor developing countries because abundant food supply later in life leads to maladaptive increase in weight and increases the risk of NCDs (146, 148, 149). The evidence is available from many developing countries. Asian Indian babies born small and with low birth weight had higher systolic blood pressure and adiposity at 8 yr of age (150). Chinese infants with low birth weight showed several cardiovascular risk factors at age 41–47 yr; hypertension, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and low levels of HDL-C (151). Furthermore, velocity of weight gain during childhood and catch-up obesity in low-birth-weight Asian Indian babies has been reported to be important for adult-onset hyperglycemia and cardiovascular risk factors (152). Whether low birth weight, childhood catch-up obesity, or increased velocity of weight gain within the normal weight range in childhood are independent factors or additive in causation of insulin resistance and the metabolic syndrome has not been investigated. These data have prompted the concept that the metabolic syndrome originates in utero and that at this time key metabolic activities may get modulated, even though the exact role of nutritional and genetic factors has not been clearly elucidated. There is preliminary evidence that programming of hormonal systems in response to an adverse fetal environment may play an important role. It is speculated that alterations in neuroendocrine responses to stress, in particular adrenocortical and sympathoadrenal responses, are associated with small size at birth, which may have influence on plasma glucose, lipid concentrations, and blood pressure. These concepts and preliminary data appear interesting but lack confirmatory evidence. Furthermore, the role of micronutrient deficiency(ies) during the perinatal period in development of chronic diseases later in life, although suggested, remains to be conclusively defined (153). Finally, preventive feeding of prepregnant and pregnant women may actually exacerbate the risk of obesity in Asian Indian neonates who have low muscle mass and excess sc adipose (68, 154). Physical inactivity Changes of occupations, advent of newer technologies, and rapid pace of urban life have increasingly resulted in more sedentary work and less energy expenditure. Leisure time activities have also shifted from outdoor play to indoor entertainment; television viewing and computer games (132). In the Philippines and China, shift to more passive commuting modes (i.e. increased motorized transportation) has increased physical inactivity (155). The household chores have become more mechanized with the use of multiple domestic automatic devices; microwave, improved food storage, washing machines, vacuum cleaners, etc., especially in India and China. Moreover, increasing mechanization even in rural areas (e.g. use of tractors than manual plowing of fields, use of motorized two-wheelers instead of bicycles) has contributed to physical inactivity in developing countries. Data from 212,021 adults from 51 countries, most of which were developing countries, in the World Health Survey (2002–2003) showed that about 15% of men and 20% of women were at risk for chronic diseases due to physical inactivity (156). The prevalence of physical inactivity at less than the levels recommended for enhancing health was high in developing countries, ranging from 17 to 91% (157). Remarkably, data from Brazil show that 70–80% of the population are inactive (158). In Colombia, an estimated 7.6% of all-cause mortality and 20.1% of mortality due to chronic diseases were attributed to physical inactivity, and an estimated 5% of the mortality due to chronic diseases were preventable if physical inactivity was reduced by 30% (159). Physical inactivity contributed to 9.6% population-attributable risk and was an important risk factor for CVD in Costa Rica (160). Finally, increase in obesity has been directly linked to physical inactivity in Chinese adults (161, 162). In most of the surveys, women are generally reported to be physically inactive than men, and this may also pertain to ethnic and cultural influences on outdoor activities. Physical inactivity was more prevalent in women than men in urban east India (85.4 vs. 75.4%) (163) and in Saudi Arabia (98.1 vs. 93.9%) (164). Immigrant women from the Middle East, including Iran and Turkey, had higher prevalence of abdominal obesity than Swedish-born women, with a high degree of physical inactivity during leisure time (165). Of major concern is that children and adolescents are rapidly showing a decrease in physical activity levels, which is fueling obesity and T2DM at a young age. Urban Asian Indian adolescents who participated regularly in outdoor games had lower prevalence of overweight, with the risk being 3 times higher in those not participating in outdoor games (166). Only 22.4% of Saudi preschool children walked 10,000 steps or more per day (167). Nearly two thirds of Iranian adolescents aged 11–18 yr were physically inactive (168). On account of cultural and weather barriers, adolescent girls had very low levels of physical activity in United Arab Emirates (169). Furthermore, nonobese Iranian children were reported to be more active in sports and went to school by foot compared with obese children who did not participate so much in sports and used mechanized transport (170). Socioeconomic factors The previously held view that people belonging to high SES are more predisposed to develop obesity in developing world is no longer tenable (171). The burden of obesity in developing countries shifts toward the people belonging to lower SES as the countrys GDP increases, probably because scarcity of food and/or physically demanding lifestyle become less common, even in people belonging to low SES after the economy improves. Pattern 5 of nutrition transition, in which nutrition and physical activity become more balanced than pattern 4, is mostly applicable to people belonging to high SES. This segment of population can afford relatively more expensive healthy foods and costly but healthy oils and avail of facilities and equipment for physical exercise and thus have far more flexibility in their choices of foods and activity patterns than those belonging to low SES. The latter class of people, although improving in economic status, continue to have low awareness of benefits of diet and physical activity and cannot afford healthier food choices (172). In Brazil, a steep increase in the prevalence of obesity has been seen in people belonging to low SES along with a decline in obesity among the higher-income groups (173, 174, 175). It is important to note that most people belonging to low SES and living in rural areas of the developing countries are lean. However, when these people migrate from rural areas to large metropolitan cities, they quickly acquire risk factors associated with urbanization despite remaining in the same SES as the previous habitat. Specifically they start smoking and consume alcohol, and their diets become imbalanced. Whereas some may still engage in physically intensive jobs, most of them are involved in sedentary jobs (e.g. stationary street hawkers). High prevalence rates of T2DM, obesity, insulin resistance, hypertension, atherogenic dyslipidemia, hyperhomocysteinemia and endothelial dysfunction have been reported by us in this intracountry rural-to-urban migrant population settled in urban slums (29, 90, 176, 177, 178, 179, 180). In particular, significant clustering of cardiovascular risk factors was seen in postmenopausal women living in urban slums in India (48, 49, 176, 181). Similar findings have been noted in the urban slum population in Thailand (130, 182). Recently, increase in obesity and cardiovascular risk factors have been seen even in rural areas of some developing countries (183). It is important to note that many of so-called rural areas are no longer truly rural, and people are increasingly becoming urbanized and mechanized even in locations far from cities. Interestingly, this phenomenon to some extent, also appears to be driven by the so-called remittance economy (money sent home from family members who have become affluent after migration, which leads to relative affluence, even in rural farm-based communities) (147). Sociocultural factors Social stigma against obesity and obsession in some developed countries to remain lean has probably helped limit obesity to some extent. However, this psychosocial attitude toward obesity is not seen in many developing countries. Studies in African-Americans show a lack of social pressure to be thin and reduced stigma toward obesity, leading to higher levels of body satisfaction and acceptance of obesity by the individual and community (184, 185, 186). For example, Gambian populations were reported to be more obesity tolerant (acceptance of obese body size as normal) than African-Americans and much more tolerant than white Americans (187). Polynesians, who have one of the highest prevalence rates of obesity in the world, equate large body size with power, beauty, and affluence (188). Similarly, there is a general misconception in parents in India and other developing countries that an obese child is a healthy child, and hence, feel that it is important to feed him/her in excess (46). Furthermore, mothers in India often have traditional belief that feeding oils, ghee (clarified butter), and butter to child would be beneficial to growth and impart strength. Another important factor is increasing pressure on children to perform in academics often forced by parents and teachers, which leads to reluctance of child to take part in sports or any other form of physical activity. Specifically, the majority of children in India are physically inactive when they are studying in classes when major examinations are held (46). Lack of playfields at school and open spaces around home, and decreased stress on games and physical training in schools has further led to decline in physical activity in children. In some developing countries, due to increasing crimes, parents do not allow children to play outside alone. Lastly, but significantly, a steep increase in sendentary activities like television viewing and computer usage has substantially contributed to a rise in obesity in children (46).
Disability, decreased quality of life, greater use of health care facilities, and increased absenteeism have been reported with obesity (189). A strong relationship between BMI and decreased physical functioning with a reduction in overall productivity has been seen (190, 191). A 6-yr study demonstrated that an obese person experiences a 50% increase in lost productivity and visits a doctor 88% more than a healthy person (192). All these factors increase health care expenditure, leading to slowing of economic growth and development and reduction of GDP; 3.5–7% of direct health care costs in the United States are due to obesity (193). When obesity causes T2DM or CVD, along with attendant complications, the direct and indirect costs rise exponentially and are unlikely to be balanced by meager health budgets and differently aligned health initiatives (more toward communicable diseases) in developing countries. In developed countries, physical inactivity and consequent diseases, including obesity, are associated with considerable economic burden and account for 1.5–3.0% of total direct health care costs (157). In a review of costs pertaining to diet-related NCDs (CVD, T2DM, and hypertension), Popkin et al. (194) placed India in a less advantageous position compared with China. According to these authors, mortality due to diet-related NCDs is expected to increase to 43.3% of all deaths by 2020 in India. The cost will rise substantially as in 1995, total cost of diet-related-NCDs (health and productivity) was $3.4 billion, costing 1.1% of the GDP in India (194). In Latin America and the Caribbean, the WHO estimated the combined annual direct and indirect costs of obesity-induced diabetes at $65.2 billion in 2000 (195). In the Pacific islands, the economic consequences of obesity and T2DM have been devastating, costing $1.95 million in Tonga and $13.6 million in Fiji, consuming nearly 60 and 39% of the health budgets, respectively (196). In mainland China, the total medical costs attributable to overweight and obesity in 2003 were estimated at 21.1 billion Yuans (approximately $2.74 billion), accounting for 25.5% of the total medical costs for chronic diseases and 3.7% of national total medical costs (197). For obesity alone, the health expenses in China were nearly $50 billion in 2000 and are projected to rise to $112 billion by 2025 (198).
Prevention of weight gain by selective interventions directed at population above average risk of developing obesity and targeted prevention directed at high risk individuals is strongly recommended. It is important to emphasize that strategies should be cost effective, culturally sensitive, and adapted to local practices, and messages imparted should be simple and in line with meager health budgets, widespread illiteracy, and unawareness in developing countries. The strategies should incorporate multiple stake holders and include government, physicians, nutritionists, schools, and nongovernmental organizations. Furthermore, intersectoral cooperation of multiple governmental departments including health, nutrition, education, agriculture, and legal is required. Clearly the potential of primary care-based programs is underused in developing countries. Contact with health professionals from an early age has been identified as one of the important strategies by the WHO for effective management of overweight and obese children. It is important to impart health education targeting mothers, who traditionally decide about dietary choices and oil purchases for the whole family in developing countries.
Strategies for children General strategies for obesity prevention in infants and young children should include promotion of breast-feeding and avoidance of use of added sugars and starches in feeding formula. Overfeeding should be avoided in stunted children. In older children, family-based and school-based health education programs (see below) incorporating healthy food choices and increased physical activity are required. Specific emphasis should be placed on limiting television viewing, promotion of fruits and vegetable intake, and restriction of energy-dense packaged snacks and sweetened carbonated beverages. Firm political will is required from the government and policy makers to carry out the following; ban on sales of junk food and sweetened beverages in and near school premises, mandatory requirement of physical fitness in schools, limiting advertisements of commercial foods on television during prime time, strict regulations regarding trans-fatty acids containing cooking oils for preparation of foods and snacks frequently consumed by children, and encouragement of research into preparation of healthy snacks by the TFCs. Greater emphasis should be placed on teaching about diet and physical exercise in school curriculum. Specifically, teenagers and young adults in urban areas (especially those studying in privately funded schools) and girls should be targeted because high prevalence of obesity has been reported in them (46). Several interventional programs have been initiated to combat obesity and the metabolic syndrome in children in developed countries. Project SPARK, Planet Health, and PATHWAYS are a few such school-based interventional programs aimed at improving several aspects of obesity-related knowledge, attitudes, and practices and have shown promising results in developed countries (199, 200, 201). There is an urgent need of such programs in developing countries as well. Of 20 interventional Chinese studies focusing on the effect of physical activity, dietary intervention, and health education in obesity in children, 17 studies were reported to be effective in reducing obesity (202). On similar grounds, in India, we have initiated comprehensive intervention programs aiming at creating awareness of childhood obesity, the metabolic syndrome, healthy nutrition, and physical activity, namely CHETNA (Children Health Education Through Nutrition and Health Awareness program) and MARG (Medical Education for Children/Adolescents for Realistic Prevention of Obesity and Diabetes and for Healthy AGing) (203). The latter is a large-scale program initiated for the first time in South Asia (aiming to cover more than 500,000 children in 15 cities in north India). In these programs, education regarding the beneficial effects of a healthy diet and increased physical activity is emphasized to children and also parents and teachers. Messages of healthy diets and lifestyle are given through attractive audiovisual programs and involvement of students in debates, skits, and drama related to health topics. Strategies for adults Both individuals and the state in the developing countries need to make serious efforts to limit the growing morbidity due to obesity and related diseases. Awareness about healthy nutrition and lifestyle should be imparted by physicians and nongovernmental organizations through their networks along with endorsed messages by famous personalities (e.g. film celebrities, sportsmen, etc.). Governmental strategies should include laws to encourage healthy oil production, discourage trans-fatty acid-based food products, and initiate food labeling with nutritive values of contents. Import duties on unhealthy oils should be increased. The TFCs should be encouraged to produce products free from trans-fatty acids. The government should improve urban planning to create more parks and tracks for jogging and cycling and sport complexes to encourage locally popular sports like football, cricket, etc. Audiovisual media can play an important role by televising healthy messages emphasizing the importance of healthy diets and physical activity and awareness about the complications of obesity and diabetes.
Prevalence of obesity and the metabolic syndrome has shown a rapid rise in developing countries in the past few decades and has led to increased risk of CVD and consequent morbidity and mortality. Because both undernutrition and overnutrition are seen simultaneously in developing countries, the double burden of diseases makes the situation more difficult. The various factors responsible for increasing NCDs are rapid nutrition transition, rural-to-urban migration, increasingly sedentary occupations and lifestyle, and maternal-fetal factors. Both genetic and environmental factors seem to contribute to it; however, the role of environment seems to be predominant. Health interventions required to prevent or reduce the morbidity/mortality need to be addressed in both children and adults. Interventions should be aimed at increasing the physical activity along with healthier food patterns and health education. Successful community-based intervention programs have been reported in developed countries, and a similar approach is required in developing countries. Reports of interventional programs in China and India, especially directed toward children, have shown encouraging results, but large-scale programs involving adults/children are required. Various other health strategies consisting of individual and community initiatives, backed up by governmental and legislative efforts, would also help in minimizing the increasing prevalence of obesity and the metabolic syndrome in developing countries.
We are grateful to Ms. Swati Bhardwaj for her contribution in providing a table on obesity in children and Mr. Om Prakash for recreating the figures.
Disclosure Statement: Both the authors have nothing to declare. Abbreviations: BMI, Body mass index; CVD, cardiovascular disease; FAO, Food and Agricultural Organization; GDP, gross domestic product; HDL-C, high-density lipoprotein cholesterol; IDF, International Diabetes Federation; IFG, impaired fasting glucose; IMCL, intramyocellular triglycerides; NCD, noncommunicable disease; NCEP, ATP III, National Cholesterol Education Program, Adult Treatment Panel III; SES, socioeconomic strata; T2DM, type 2 diabetes mellitus; TFC, transnational food company; WHO, World Health Organization. Received July 23, 2008. Accepted September 11, 2008.
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