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Nestlé Nutrition Institute Workshop SeriesPediatric Program Volume 63
Emerging Societies -Coexistence ofChildhoodMalnutrition andObesity
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© 2008, Nestec Ltd., Vevey, Switzerland
Nestlé Nutrition Institute Workshop SeriesPediatric Program Volume 63
Emerging Societies – Coexistence of Childhood Malnutrition and Obesity
New Delhi, March 30–April 3, 2008
EditorsSatish C. KalhanAndrew M. PrenticeChittaranjan S. Yajnik
Contents
iv Foreword
1 Global Changes in Diet and Activity Patterns as Drivers of the Nutrition TransitionBarry M. Popkin
5 Regional Case Studies – IndiaK. Srinath Reddy
9 Regional Case Studies – ChinaShi-an Yin
11 Regional Case Studies – AfricaAndrew M. Prentice
13 Evolutionary Origins and the Impact of a Rapid Nutrition TransitionAndrew M. Prentice
15 Prenatal Origins of UndernutritionParul Christian
17 Postnatal Origins of UndernutritionMarc-André Prost
20 Malnutrition, Long-Term Health and the Effect of Nutritional RecoveryAna Lydia Sawaya
23 Epigenetic Inheritance and the EnvironmentSuyinn Chong, Alyson Ashe, Nathan Oates, Marnie Blewitt, Nicola Vickaryous and Emma Whitelaw
25 Methionine in Development, Protein Restriction, and in Fatty Liver DiseaseSatish C. Kalhan
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27 Adiposity and Comorbidities: Favorable Impact of Caloric RestrictionEric Ravussin
29 Obesity, Inflammation, and MacrophagesVidya Subramanian and Anthony W. Ferrante, Jr.
33 Obesity, Hepatic Metabolism and DiseaseJohn M. Edmison, Satish C. Kalhan and Arthur J. McCullough
36 The Imperative of Preventive Measures Addressing LifecycleChittaranjan S. Yajnik
39 New Approaches to Optimizing Early DietsStaffan Polberger
41 Prevention of Low BirthweightDewan S. Alam
44 Community-Based Approaches to Address Childhood Undernutrition and Obesity in Developing CountriesPrakash Shetty
47 List of Speakers
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Foreword
Three Nestlé Nutrition Institute Workshops have addressed the topics of obesity and malnutrition; namely the 49th NNW in 2001 on ‘Obesity in Childhood and Adolescence’, and ‘The Malnourished Child’ and ‘Linear Growth Retardation in Less Developing Countries’ in the 1980s. Since then, the problems of malnutrition and obesity and their associated health issues have worsened. The WHO estimates that 22 million children under 5 years of age are overweight at present. In the USA the number of overweight children has doubled since 1980. Despite an overall decrease in the prevalence of stunting in developing countries since 1980, childhood malnutrition remains at a disturbingly high level and as such a major public health problem. The coexistence of these two major public health concerns lead us to organize the 63rd Nestle Nutrition Institute Workshop entitled ‘Emerging Societies – Coexistence of Childhood Malnutrition and Obesity’.
The coexistence of undernutrition (low birthweight, poor growth) alongside overnutrition (mainly obesity) is a phenomenon afflict-ing many countries as their economies develop and food availability increases. This phenomenon, otherwise known as the ‘nutrition tran-sition’, is becoming increasingly prevalent in many emerging nations. To date, community-based interventions are the most widely used approaches to counteract malnutrition. However, evidence is grow-ing that interventions targeting the improvement in maternal nutrition and health may deliver the most promising results for improving child nutrition. The nutrition transition now poses the challenge of how to balance short-term benefits versus long-term risks of increased meta-bolic diseases. India was cited as an example to demonstrate the mag-nitude of potential long-term consequences, with a 300% increase in the prevalence of diabetes amounting to an estimated 80 million cases by 2025. The contribution not only of nutritional factors, but also genetic background and epigenetic factors, to these outcomes were addressed. In this context, hypotheses such as the thrifty gene hypoth-esis were discussed as potential mechanisms to explain the increased susceptibility to obesity in emerging nations.
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Considerable research still lies ahead in order to address the ques-tion of which population segments and at what stage(s) of their life-cycle should be targeted in order to have the most impactful results.
We are deeply indebted to the three chairpersons of this work-shop: Prof. Satish Kalhan from the Case Western Reserve University in Cleveland; Prof. Andrew Prentice from the London School of Hygiene, and Prof. Chittaranjan Yajnik from the King Edward Memorial Hospi-tal in Pune, experts recognized worldwide in their respective fields in nutrition research. Our warm thanks go also to Dr. Natalia Wagemans and her team for their excellent logistic support of the workshop and for enabling the participants to enjoy the wonderful Indian culture.
Dr. Petra Klassen, PhDChairman Scientific AdvisorNestlé Nutrition Institute Nestlé Nutrition InstituteVevey, Switzerland Vevey, Switzeralnd
Prof. Ferdinand Haschke, MD, PhD
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Global Changes in Diet and Activity Patterns as Drivers of the Nutrition Transition
Barry M. Popkin
The Nutrition Transition
The nutrition transition covers the shifts in the way we eat and move and subsequent effects on our body composition over man’s history [1]. In the 20th century, in most poor and all middle and high income countries, the populations were dominated by the emergence of nutrition-related non-communicable diseases (NR-NCDs).
The Dietary Drivers: More Fats, More Added Caloric Sweeteners, More Animal-Source Foods
Edible oil has been a major source of dietary change in the lower and middle income countries in the last several decades. The recent shift in the pattern of the nutrition transition in developing countries typically begins with major increases in the domestic production and imports of oilseeds and vegetable oils, rather than meat and milk. The global availability of soybean, sunflower, rapeseed, and palm oil has approximately tripled between 1961 and 1990 and continued to increase since then, though at a slightly reduced global pace. See table 1 for the dietary and physical activity pattern data for China.
Caloric sweeteners in 2000 were consumed on a daily basis of 306 kcal/capita across the globe. Figures that underestimate the con-sumption based on much higher quality diet data. The shift to caloric beverages as the source of calories is particularly important because they do not sate us and there is an emerging consensus that calories from beverages are a potential source of energy imbalance globally. This is true whether the calories come from high fat, high protein or high carbohydrate beverages.
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Animal source foods (ASF): The revolution in ASF refers to the increase in demand and production of meat, poultry, fish, and milk in low-income developing countries. Most of the world’s growth in production and consumption of these foods comes from the developing countries.
Underlying Eating Behaviors
We have begun to see rapid shifts in the way people eat in terms of location, methods of cooking, and frequency of intake [2]. Frying is rapidly displacing more healthful cooking methods, snacking and away-from-home consumption are up significantly.
Physical Activity Dynamics: Changes in the Technology of Work and Movement and Leisure
Declines in physical activity are particularly profound across market work, but significant changes also have been shown in work at home, leisure, and transportation – each affecting significantly increases in obesity.
Market work: The proportion of individuals working in energy expenditure-intensive jobs such as farming, mining, and forestry is
Table 1. Dietary and physical activity trends of Chinese adults aged 20–45 years
1989 2006
Food consumption Plant oils, g/day 014.8 030.9 All calories per capita from edible oil, % 004.9 012.4 Beef and pork, g/day 052.1 070.6 Poultry, g/day 004.4 009.3 Fish + other aquatic products, g/day 014.4 018.3 Eggs, g/day 009.4 025.1 Dairy, g/day 001.6 011.6 Total animal source foods 102.4 140.5
Physical activity Adults in light level occupations, % 024.7 040.0 Households with color TV, % 020.5 095.7 Households with washing machine, % 036.8 072.8 Households with refrigerator, % 013.3 052.7
Source: China Health and Nutrition Survey.
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way down while manufacturing has increased slightly, but the major shift is toward lower activity service sector jobs. Equally important has been a major shift in the activity of each occupation [3].
Work at home: Time in food preparation has declined over the past half century from about 2 h/day to less than a 0.5 h in the US and variable amounts elsewhere. Time-saving home technologies affect cooking, cleaning, and shopping time [3].
Transport shifts from active to passive: In most countries the proportion of individuals walking to work or shopping and other activ-ities has declined drastically [4].
Leisure is a major global focus for obesity control but is it earned: There is little leisure time in most of our low and middle income devel-oping countries and a key issue will be how to expand this in a health-ful manner. For children, studying, computers, TV viewing and gaming are all important. For adults TV viewing is becoming more important, but its impact is poorly documented.
Figure 1 shows shifts in METS of physical activity changes for Chinese men. The changes in urban and rural areas are comparable.
References
1 Popkin BM: Global nutrition dynamics: the world is shifting rapidly toward a diet linked with noncommunicable diseases. Am J Clin Nutr 2006;84:289–298.
2 Wang Z, Zhai F, Du S, Popkin BM: Dynamic shifts in Chinese eating behaviors. Asia Pacific J Clin Nutr, in press.
200
250
300
350
400
450
500
ME
T,
h/w
eek
Leisure activity
Travel activity
Domestic activity
Occupational activity
1991 1993 1997 1997 2000 2004 2006
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Fig. 1. Shift in MET hours per week by activity among Chinese men (18–55 years old).
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3 Monda KL, Zhai F, Popkin BM: Longitudinal relationships between occupa-tional and domestic physical activity patterns and overweight status in China. Eur J Clin Nutr 2007 Jul 18 [Epub ahead of print].
4 Bell AC, Ge K, Popkin BM: The road to obesity or the path to prevention: motorized transportation and obesity in China. Obes Res 2002;10:277–283.
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Regional Case Studies – India
K. Srinath Reddy
As a proportion of all deaths in India by the year 2020, cardiovas-cular disease (CVD) will be the largest cause of disability and death [1]. At the present stage of India’s health transition, chronic diseases contribute to an estimated 53% of deaths and 44% of disability-adjusted life-years lost. India also has the highest number of people with diabe-tes in the world, with an estimated 19.3 million in 1995 and projected 57.2 million in 2025. On the basis of recent surveys, the Indian Coun-cil of Medical Research estimates the prevalence of diabetes in adults to be 3.8% in rural areas and 11.8% in urban areas. The prevalence of hypertension has been reported to range between 20 and 40% in urban adults and 12 and 17% among rural adults. The number of people with hypertension is expected to increase from 118.2 million in 2000 to 213.5 million in 2025, with nearly equal numbers of men and women. Over the coming decade, until 2015, CVD and diabetes will contribute to a cumulative loss of USD 237 billion for the Indian economy. Much of this enormous burden is already evident in urban as well as semi-urban and slum dwellings across India, where increasing lifespan and rapid acquisition of adverse lifestyles related to demographic transi-tion are contributing to the rising prevalence of CVDs and its risk fac-tors such as obesity, hypertension, and type 2 diabetes. The underlying determinants lie in socio-behavioral factors such as smoking, physical inactivity, improper diet and stress [2].
Unhealthy diets and physical inactivity are two of the main risk fac-tors for increased blood pressure, increased blood glucose, abnormal blood lipids, overweight/obesity, and for the major chronic diseases such as CVDs, cancer, and diabetes [3]. Globally it is estimated that approximately 2.7 million deaths are attributable to low fruit and veg-etable intake while 1.9 million deaths are attributable to physical inac-tivity. A large majority of these deaths occurs in low and middle income countries. The changes in diet and physical activity have resulted largely from epidemiological transition that is underway in most low income countries including India. The main driving forces of these
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epidemiological shifts are a globalized world, rapid and uneven urban-ization, demographic shifts and inter- and intra-country migrations – all of which result in alterations in dietary practices (a shift from high fiber, vegetable and fruit-rich diets to diets rich in saturated fats, trans fats and high salt-containing processed foods) and a decrease in physical activity (due to availability of mass transport systems and mechaniza-tion of daily activities). While these changes are global, India has sev-eral unique features. The transitions in India are uneven with several states in India still battling the ill effects of under nutrition and infec-tious diseases, while in other states with better indices of development, chronic diseases including diabetes are emerging as major areas of con-cern. Regional differences and urban-rural differences in the occurrence of CVD is the hallmark. There is marked heterogeneity in total energy intake in both rural and urban areas. Assam, Gujarat, Kerala, Maharash-tra and Tamil Nadu have the lowest rural average caloric intake as com-pared to mean intakes in Punjab or Haryana (tables 1, 2).
Figures 1 and 2 show comparisons between the rural and urban averages per capita fat and protein intakes, respectively.
All these differences result in a differing prevalence of CVD and its risk factors. For example even among industrial workers and their
Table 1. Change in average calorie consumption by states – rural (kcal/capita and day)
1972–1973 1983 1993–1994 1999–2000
Andhra Pradesh 2,103 2,204 1,052 2,021Assam 2,074 2,055 1,983 1,915Bihar 2,225 2,189 2,115 2,121Gujarat 2,142 2,113 1,994 1,986Haryana 3,215 2,554 2,491 2,455Karnataka 2,202 2,260 2,073 2,028Kerala 1,550 1,884 1,955 1,982Madhya Pradaan 2,423 2,323 2,164 2,062Maharashtra 1,895 2,144 1,938 2,012Orissa 1,995 2,103 2,199 2,119Punjab 3,493 2,577 2,418 2,381Rajasthan 2,730 2,433 2,470 2,425Tamil Nadu 1,955 1,861 1,884 1,826Uttar Pradesh 2,575 2,399 2,307 2,327West Bengal 1,921 2,027 2,211 2,095
Source: Chandrashekhar and Ghosh [5].
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families who are economically better off than the general community, there are wide-ranging differences in CVD risk factors. In industries located predominantly in urban localities, CVD risk factor levels are high as compared to those in peri-urban locations [4]. However local
Table 2. Change in average calorie consumption by states – urban (kcal/capita and day)
1972–1973 1983 1993–1994 1999–2000
Andhra Pradesh 2,143 2,009 1,992 2,052Assam 2,135 2,043 2,108 2,174Bihar 2,157 2,131 2,088 2,171Gujarat 2,172 2,000 2,027 2,058Haryana 2,404 2,242 2,140 2,172Karnataka 1,925 2,124 2,025 2,045Kerala 1,723 2,048 1,966 1,995Madhya Pradesh 2,229 2,137 2,082 2,132Maharashtra 1,971 2,028 1,989 2,039Orissa 2,275 2,219 2,251 2,298Punjab 2,783 2,100 2,089 2,197Rajasthan 2,357 2,255 2,184 2,335Tamil Nadu 1,841 2,140 1,922 2,030Uttar Pradesh 2,161 2,043 2,114 2,131West Bengal 2,080 2,048 2,131 2,134
Source: Chandrashekar and Ghosh [5].
1972–1973
10
20
30
40
50
60
1983 1993–1994 1999–2000
Urban
Rural
Fig. 1. Average all-India per capita fat consumption (g/day). Source: FAO [6].
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dietary practices may alter the prevalence. For example, tea garden workers of Assam receive extra salt as compensation for the putative loss of sodium due to their outdoor work. This has resulted in high prevalence of high blood pressure though other CVD risk factors are similar to other industrial populations which are predominantly located in peri-urban areas.
Therefore while studying nutrition and physical activity shifts in India, the marked heterogeneity and secular changes in dietary and physical activity practices should be taken into account. This princi-ple should also apply to strategies, policies and nutrition and physical activity guidelines so that they take regional differences into account.
References
1 Lopez AD, Mathers CD, Ezzati M, et al (eds): Global Burden of Risk Factors. Washington, Oxford University Press/World Bank, 2006.
2 Reddy KS, Shah B, Varghese C, Ramadoss A: Responding to the threat of chronic diseases in India. Lancet 2005;366:1744–1749.
3 WHO 20074 Reddy KS, Prabhakaran D, Jeemon P, et al: Educational status and cardiovas-
cular risk profile in Indians. Proc Natl Acad Sci USA 2007;104:16263–16268.5 Chandrashekhar CP, Ghosh J: The calorie consumption puzzle. The Hindu,
Feb 11, 2003.6 FAO 2003.
1972–1973
54
56
58
60
62
64
1983 1993–1994 1999–2000
Rural
Urban
Fig. 2. Average all-India per capita protein consumption (g/day). Source: FAO [6].
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Regional Case Studies – China
Shi-an Yin
The status of childhood malnutrition and obesity in China is reviewed according to the 2002 National Nutritional and Health Survey in China [1–3] and data from a national survey on the health and physi-cal fitness of Chinese students in 2005 [4]. Between 1979 and 2008 a rapid change in economic development has been seen in China, and characteristic of this transition period is the significant increase in the prevalence of chronic non-communicable diseases. Compared with the results in 1992, the body weight and height of preschool children in urban and rural areas were significantly improved; the prevalence of malnutrition (underweight and stunting) in urban and rural areas was significantly reduced; the national average prevalence of overweight and obesity for the children under 6 years was 3.4 and 2.0%, respec-tively, as estimated by the Chinese and WHO standards (fig. 1, 2) [1, 5]; a deficiency in micronutrients, including calcium, zinc, vitamin A, vita-min B1 and B2, is rather common in the preschool and school children. The current data show that the growth and development of Chinese
0 1 2 3
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4 5 6 7
Overweight (C)
Overweight (W)
Obesity (C)
Obesity (W)
OW/Ob (C)
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7–17 years
0–6 years
Fig. 1. The prevalence of overweight and obesity in children and adoles-cents (%). OW = Overweight; Ob = obesity; C = using the Chinese standard; W = using the WHO standard.
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children is far from ideal. We are now facing double challenges: malnu-trition and the increase in overweight and obesity in children.
References
1 Wang LD: The General Report in the Nutritional and Health Status of the Chinese Population – 2002 National Nutrition and Health Survey. Beijing, People’s Medical Publishing House, 2005.
2 Zhai FY, Yang XG: The status of dietary and nutrient intakes of the Chinese population – 2002 National Nutrition and Health Survey. Beijing, People’s Medical Publishing House, 2006.
3 Yang XG, Zhai FY: The body mass and nutrition status of the Chinese popula-tion – 2002 National Nutrition and Health Survey. Beijing, People’s Medical Publishing House, 2006.
4 Ji CY, Sun JL: Analyses of the epidemiological status of overweight and obesity in Chinese students and the prevalence. J Peking Univ Health Sci 2004;36:194–197.
5 Chen CM, He W, Fu ZY, et al: Ten-Year Tracking Nutritional Status in China. Beijing, People’s Medical Publishing House, 2004.
7–17 years
0–6 years
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%
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Rural (OW)
Total (Ob)
Urban (Ob)
Urban (OW)
Rural (Ob)
Fig. 2. The prevalence of overweight and obesity in children and adoles-cents estimated by the Chinese standard in different areas. OW = Overweight; Ob = obesity.
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Regional Case Studies – Africa
Andrew M. Prentice
Africa is the final continent to be affected by the nutrition transi-tion and, like others that have passed through this phase previously, is characterized by the paradoxical coexistence of malnutrition and obesity. This is vividly apparent by a visit to almost any major hospital in urban Africa where children’s wards are struggling to rehabilitate severely malnourished children whilst neighboring adult wards are dealing with amputations of diabetic feet and other consequences of obesity-related comorbidities.
In sub-Saharan Africa, progress towards meeting one of the key indicators of the first Millennium Development Goals – the proportion of underweight children – is slow and in several countries is in reverse. Current projections indicate that Africa will not meet its target by 2015. Africa is still the home of the most acute nutritional emergencies with unacceptably high levels of severe-acute malnutrition in many regions of conflict and in countries failed by their political leaders.
Proportions of the adult population with a body mass index of <18.5 (set as the definition of chronic energy deficiency) are sub-stantial, but less than in many South Asian countries, and are a lesser concern. Adult height is also greater than in many Asian countries. In mothers the larger adult stature than in the Indian sub-continent is accompanied by larger mean birthweights and a lower proportion of low birthweight babies. This may be significant in terms of the rate at which Africa can emerge from the nutrition transition. It is arguable that Africa will suffer a lesser burden of chronic disease than Asia in which the ‘Developmental Origins of Health and Disease’ thesis pre-dicts a major future burden of chronic disease based upon the mis-match between the fetal and adult nutritional environment.
Yet obesity rates in Africa are escalating fast. The increase is espe-cially rapid in urban areas, though the trends are by no means confined to Africa’s cities. There are several features of the obesity epidemic in Africa that mirror those in other emerging nations: it penetrates the richer nations first (in Africa these tend to be in North Africa); it
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penetrates urban areas first with a strong urban-rural gradient, but this diminishes with time; initially it affects the wealthy, but later there is a demographic switch and obesity becomes a condition more associ-ated with poverty (as in Western nations), and it shares many of the same drivers related to the increasing affordability of highly refined oils and carbohydrates, and a move away from subsistence farmwork and towards sedentary lifestyles.
Africa also has some characteristics of the obesity epidemic that stand out from other regions as follows. (1) Africa is probably the only region in which obesity (especially among women) is viewed cultur-ally as a positive and desirable trait. This leads to major gender dif-ferences in obesity rates in many countries, and fuels a syndrome of intentional weight gain in young women. (2) Most of Africa has very low rates of obesity in children. To date African obesity is mostly an adult syndrome. (3) Africans seem genetically prone to higher rates of diabetes and hypertension in association with obesity than Cauca-sians, but seem to be relatively protected from dyslipidemias. (4) The case-specific deaths and disabilities from diabetes and hypertension in Africa are very high due to the paucity of health services and the strain that the ‘double burden’ of disease places on health systems. (5) Recent data suggest that some non-African races may have evolved recently to select genetic traits that offer them some protection from obesity and diabetes, but that these traits have not been under positive selection in Africans.
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Evolutionary Origins and the Impact of a Rapid Nutrition Transition
Andrew M. Prentice
There are many obvious and plausible reasons (and some less obvious ones) that may account for the rapid increase in obesity rates in developing and emerging nations. Changes in diet and activity pat-terns brought about by the economic transition have been previously discussed in this symposium by Popkin. In later papers we will explore the possibility that undernutrition in fetal and early life can reset the metabolic phenotype in ways that make people especially vulnerable to the influences of an obesogenic environment if they escape from the frugality of a subsistence living.
This paper seeks to answer whether people from developing countries may have a genetic predisposition to obesity and its most common clinical outcome, type 2 diabetes mellitus (T2DM).
The concept of ‘thrifty genes’, first proposed by Neel [1] in the 1960s, has been prominent amongst the various theories proposed to explain the sudden rise in global obesity levels in the late 20th cen-tury. The basic premise of the thrifty gene hypothesis is that an ability to rapidly deposit energy as body fat in times of plenty would have assisted individuals to survive periods of starvation, and hence would have been under positive natural selection. Many of the earlier propo-nents of the theory used it to explain why certain populations had very high levels of obesity and diabetes. For instance, it was suggested that modern Polynesian Islanders are the product of a small founder group that had survived starvation during the long sea journeys across the Pacific as the islands were first colonized.
Contemporary interpretations of the thrifty gene story [2] propose that: (a) almost all ancient populations have been frequently subjected to selective pressure by famine, especially since the dawn of agricul-ture, and hence thriftiness is likely to affect all racial groups in some form; (b) that transmission is unlikely to have been strongly selected by mortality within famines (viability selection) and is much more likely to have been due to fertility selection mediated through the
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powerful effects of regular annual hungry seasons, or episodic starva-tion, on female fecundity, and (c) that the concept of thriftiness (which is generally interpreted in relation to saving of energy) should also encompass an element of the ‘greedy gene’ since disregulated appetite control systems are the most common cause of the genetically based human obesity syndromes so far identified.
It must be stressed that the thrifty gene concept lacks any experi-mental validation to date and that there are no data to suggest that racial and ethnic groups currently undergoing the nutrition transition (e.g. native Africans and Asians) have a particular genetic predisposi-tion to obesity. However the latest findings in relation to the FTO gene (the first of the multigenic contributors to human obesity to be iden-tified with certainty) strongly suggest that the variant that promotes leanness is only carried by Caucasians. This may be in line with Dia-mond’s [3] suggestion that Caucasians have been selected to have a lower susceptibility to T2DM, though the likely origins of such putative selection remain a mystery.
Exciting times lie ahead with respect to understanding whether or not evolution has endowed any of us with particular susceptibil-ity to obesity. New statistical methods for comparing genome-wide scans between different ethnic/racial groups are starting to pinpoint those genes that show evidence of recent differential selection. These will soon assist in interpreting whether past famines and food scarcity have created specially vulnerable populations.
Whether such knowledge would ever influence the public health messages and government initiatives required to combat obesity remains a moot point. We already have strong evidence that urban populations in developing countries do exhibit high levels of obesity, and this fact alone should drive the public health agenda.
References
1 Neel JV: Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘prog-ress’. Am J Hum Genet 1962;14:353–362.
2 Prentice AM, Rayco-Solon P, Moore SE: Insights from the developing world: thrifty genotypes and thrifty phenotypes. Proc Nutr Soc 2005;64:153–161.
3 Diamond J: The double puzzle of diabetes. Nature 2003;423:599–602.
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Prenatal Origins of Undernutrition
Parul Christian
Childhood undernutrition including stunting and wasting contin-ues to be high in many regions of the developing world. Overall, 178 million children under 5 years of age throughout the developing world are estimated to be stunted and 19 million are severely wasted. Birth-weight, a common proxy measure of intrauterine growth, is commonly low in the same regions of the world where childhood undernutrition exists. Low birthweight (<2.5 kg) caused either by preterm birth or intrauterine growth restriction affects immediate survival and func-tion and is a determinant of later life risk of chronic diseases including type 2 diabetes and cardiovascular diseases. Birth size is influenced by numerous prenatal factors including maternal nutritional, environ-mental and lifestyle exposures during pregnancy and infection. Mater-nal pre-pregnancy weight and height are independently and directly associated with birthweight and are also known to modify the effects of pregnancy weight gain and interventions during pregnancy on birth-weight and perinatal mortality. Few studies have examined nutritional interventions beginning in the pre-periconceptional phase for out-comes such as gestational duration and birthweight. Maternal diet dur-ing pregnancy, specifically of micronutrient-rich foods such as milk, and fruits and vegetables, may also enhance birth outcomes. Other prenatal factors commonly known to impact birthweight in develop-ing countries include maternal age, parity, sex, and birth interval. In many settings early marriage and pregnancy are a norm resulting in a substantial proportion of pregnancies occurring during adolescence when competition for nutrients for growth of the mother and the fetus is high, especially in environments where food availability is low. Life-style factors such as physical activity and maternal stress, as well as environmental toxicants have variable influences on birth outcomes. Tobacco and other substance use can reduce gestational duration and be deleterious to fetal growth. Infections, specifically ascending repro-ductive tract infections, malaria and, increasingly, HIV can cause pre-term and intrauterine growth restriction (IUGR) in many settings. Few
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studies have examined the contribution of birthweight and prenatal maternal nutritional status to childhood stunting and wasting. Studies have generally found adjusted odds ratios for low birthweight rang-ing between 2 and 5. In other words, after adjusting for determinants of childhood undernutrition including feeding practices and morbid-ity, being born low birthweight continues to carry a two- to fivefold increased risk of stunting in many developing country settings. Even fewer studies have examined birth length or maternal nutritional status as risk factors. More research is needed to determine the proportion of childhood undernutrition attributable to IUGR in different settings in order to better target interventions to appropriate life stages for com-bating childhood undernutrition.
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Postnatal Origins of Undernutrition
Marc-André Prost
Emerging countries are undergoing a rapid nutrition transition. Non-communicable diseases are the leading causes of death, but underweight together with iron, zinc and vitamin A deficiencies are still among the 15 biggest killers. Undernutrition impairs physical growth, increases morbidity and mortality, impairs cognitive develop-ment, reduces economic productivity, and, later, increases the risk of chronic diseases and impacts on offspring birthweight. In this chapter I review how inadequate nutrition, infection, and inappropriate mother–child interactions are the main drivers of undernutrition in childhood. Underlying socioeconomic, environmental and genetic factors are also explored. Some perspectives on how urbanization and globalization may affect undernutrition are discussed.
Globally, length starts to falter immediately after birth while weight starts faltering around 3–6 months, suggesting very different eti-ologies [1]. Breast milk provides enough energy and protein for growth during the first 6 months. In deficient populations, infants’ micronutri-ent stores at birth and intakes through breast milk may not suffice to cover the needs for optimal linear growth. Among the 2–5 months age group, early introduction of complementary foods affects both weight and length growth by reducing the quality and quantity of the diet, and increasing infection incidence. Beyond 6 months of age, complemen-tary foods fail to provide enough energy and other nutrients to meet the increasing needs for growth and activity. Poor energy intakes are associated with wasting while micronutrient imbalances affect linear growth. Iron and zinc have been consistently identified as ‘problem nutrients’ in the 6–23 months age group worldwide [2].
Infections are strongly associated with growth faltering. Diarrheal diseases show the strongest association with short-term weight defi-cit. Other acute and chronic infections impact differently on growth. Effects are greater in high prevalence settings as well as in nutrition-ally compromised children [3]. The severity, duration, frequency, and type of infection are key factors mediating the effect on growth by
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increasing nutrient requirements, losses, and impairing intakes and absorption.
Care provided to children, defined by maternal endogenous fac-tors and societal determinants, affects growth [4]. Maternal influences include education, health status, and self-confidence. Between mater-nal and societal determinants are maternal workload, time availability, and maternal autonomy and control of resources. The level of social support received by mothers also impacts on care quality.
Factors at the national level explain most of the undernutrition variability between countries, including lower energy availability, lower female literacy rates, lower gross domestic product, or lower vaccination coverage [5]. Other factors consistently correlated with undernutrition include access to safe water, healthcare, sanitation, but also parity, birth spacing, birth order, and marital status. Maternal size at birth has been shown to influence birth size in their offspring, suggesting a transgenerational effect of undernutrition [6]. Weight and length show marked seasonal variations in agro-pastoral communi-ties. Weight variations have been correlated with the timing of low-est food availability and periods of highest diarrhea incidence in many countries.
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0.5
0.75
1
�0.25
1.25
0
3 6 9 12 15 18 21 24 27 30 33
Age (months)
Z s
co
re (N
CH
S)
36 39 42 45 48 51 54 57 60
Weight for length
Weight for age
Length for age
Fig. 1. Worldwide timing of growth faltering. Mean anthropometric z scores by age relative to the NCHS reference (0–59 months) in 39 nationally representative surveys conducted in Latin America, Asia, and Africa from 1987 to 1997. Reproduced with permission from Shrimpton et al. [1].
19
In 2008 the proportion of the urban population will equal the rural population. In developing countries more than 30% of the urbanized live in shanty towns, meaning higher transmission rates of infections due to a lack of water, poor housing conditions, overcrowding, poor hygiene, and environmental pollution. Urbanization also affects behav-ior. For instance the duration of breastfeeding is lower in urban than rural settings. Although trade globalization has meant greater food availability, it has also increased the vulnerability to global price fluc-tuations. Nowadays a booming demand for oil and food commodities from emerging countries drives global prices up. How it will affect the poorest countries is unknown, but they surely are ill equipped to face a global competition for dwindling resources.
The burden of child undernutrition remains so great that there is a renewed moral urgency to find integrated solutions to tackle the prob-lem. Over- and undernutrition are now seen as different manifestations of a global phenomenon. Since they are linked, fighting undernutrition should impact positively on both outcomes.
References
1 Shrimpton R, Victora CG, de Onis M, et al: Worldwide timing of growth falter-ing: implications for nutritional interventions. Pediatrics 2001;107:e75.
2 Dewey K, Brown K: Update on technical issues concerning complementary feeding of young children in developing countries and implications for inter-vention programs. Food Nutr Bull 2003;24:5–28.
3 Bhan MK, Bahl R, Bhandari N: Infection: How important are its effects on child nutrition and growth?; in Martorell R, Haschke F (eds): Nutrition and Growth. Nestlé Nutr Workshop Ser Pediatr Program. Philadelphia, Lippincott Williams & Wilkins, 2001, vol 47, pp 197–221.
4 Engle PL, Menon P, Haddad LJ: Care and Nutrition: Concepts and Measurements. Washington, IFPRI, 1997.
5 Frongillo EA, de Onis M, Hanson KMP: Socioeconomic and demographic fac-tors are associated with worldwide patterns of stunting and wasting of chil-dren. J Nutr 1997;127:2302–2309.
6 Ramakrishnan U, Martorell R, Shroeder DG, et al: Role of intergenerational effects on linear growth. J Nutr 1999;129(suppl):544S–549S.
20
Malnutrition, Long-Term Health and the Effect of Nutritional Recovery
Ana Lydia Sawaya
Worldwide malnutrition is responsible for 50% of deaths in child-hood. The prevailing type of malnutrition is stunting, which stands out as an indicator not only of malnutrition, but also of poverty. The causes for stunting are: insufficient nutrition of the mother; intrauter-ine malnutrition; lack of breastfeeding until the child is 6 months old; late introduction of complementary foods; inadequate quantity and quality of complementary foods, and nutrient absorption impaired by infections and intestinal parasitic diseases. The data on malnourished children being treated at a center for recovery from malnutrition in São Paulo, Brazil (CREN), showed that over 70% were born with low or insufficient weight. CREN is a center that offers treatment to slum children with mild to severe malnutrition. Pediatricians, nutrition-ists, social workers and psychologists participate in the treatment. The pediatrician monitors the clinical status, laboratory findings and anthropometric progress of each child. The nutritionist follows the child’s diet and corrects the problems identified during treatment. Laboratory tests (blood and stools) are done in each semester. The children also receive Fe and vitamin (A, B, C and D) supplements in prophylactic doses. The children are either treated in an outpatient clinic or in a day-hospital. The children treated in the day-hospital are more severely malnourished. Data from CREN showed that, among the moderately malnourished children under treatment, about 80% had at least one infectious episode in the previous month and, among the severely malnourished ones, that prevalence rose to about 90%. The difference in the severity of malnutrition referred mainly to the rate of infections. 60% of these children also had parasites. Another very com-mon occurrence was anemia, which was verified in 62% of them.
It was estimated that 51.7 million people lived in slums in Bra-zil in 2003. This population is growing faster than the urban one. This condition is associated with poor sanitation, bad food habits, lower birthweight and stunting. Longitudinal and cross-sectional studies in
21
stunted adolescents have shown the high susceptibility to gain cen-tral fat, lower fat oxidation and lower resting and postprandial energy expenditure. In addition, higher blood pressure, higher plasma uric acid and impaired flow-mediated vascular dilation were all associated with a higher level of hypertension in low birthweight and stunted children. Stunted boys and girls also showed lower insulin production by pancreatic � cells. All these factors are linked with a higher risk of chronic diseases later in life. Among stunted adults alterations in plasma lipids, glucose and insulin were also present.
Combining all these findings we can say that insufficient con-sumption during growth causes stress in the organism, leading to an increase in the cortisol-to-insulin ratio. As is well known, malnutrition is a powerful stress stimulator and causes an increase in the cortisol levels and its catabolic action, to direct energy as glucose to brain. Besides, food deficiency reduces the anabolic action of tissue synthe-sis that depends on insulin, causing wasting. That hormonal balance leads to a reduction in the hormone responsible for growth, insulin-like growth factor-1 (IGF-1). The high cortisol-to-insulin ratio and low IGF-1 also reduce muscle mass gain and linear growth, besides increas-ing the waist-to-hip ratio and reducing body fat oxidation. If a child in that condition starts to ingest a ‘modern’ diet and presents physical inactivity due to urban living conditions, an excessive fat gain will take
f Energy intake
during growth �
Short stature
Obesity
Hypertension
Diabetes
F Fat gainF Waist:hip
ratio
f Linear
growth
f Muscle
gain
f Fat
oxidation
F Cortisol:insulin
f IGF-1
Kidney/
vascular
changes
Western diet
and/or
physical inactivity
Fig. 1. Association between short stature, obesity, hypertension and diabetes.
22
place, which can result in an association between stunting, obesity, hypertension and diabetes (fig. 1).
Recent studies in children who had an adequate nutritional recov-ery with linear catch-up growth, after treatment in the nutritional rehabilitation center, CREN, showed that the alterations in body com-position, bone density and insulin production (found in non-treated stunted children) were no longer apparent.
23
Epigenetic Inheritance and the Environment
Suyinn Chong, Alyson Ashe, Nathan Oates, Marnie Blewitt , Nicola Vickaryous and Emma Whitelaw
Hypothesized as a possible interface between the genetic and environmental factors that give rise to phenotype, the field of epigenet-ics is being heralded as the explanation for hitherto poorly understood instances of non-Mendelian inheritance. There exists a small group of genes, known as metastable epialleles, which are sensitive to envi-ronmental influences, such as diet, and undergo molecular changes that remain for the life of the individual. These modifications are called epigenetic and in some cases they survive across generations, that is, through meiosis. This is termed transgenerational epigenetic inheritance. These findings have led to the temptation to infer similar processes in humans. Although it seems clear that the lifestyle of one generation can significantly influence the health of the next generation in humans, in the absence of supporting molecular data, it is hard to justify the idea that this is the result of transgenerational epigenetic inheritance in the light of other, more plausible explanations. What is required first is to identify genes that are sensitive to the epigenetic state, that is, metastable epialleles, in humans. Methods are emerg-ing by which we can do this. In light of the paucity of evidence, when extrapolating results seen in mice to humans, we should proceed with caution.
24
Fig. 1. Chromatin proteins and epigenetic modifications attached to the double-stranded DNA.
25
Methionine in Development, Protein Restriction, and in Fatty Liver Disease
Satish C. Kalhan
The coexistence of intrauterine and neonatal malnutrition, and the development of obesity and type 2 diabetes in adults, has been con-firmed in a number of studies in humans and animal models. Although the exact mechanism of such imprinting has not been understood, data from animal studies suggesting hypermethylation of the genomic DNA suggest that epigenetic changes may be responsible for such pattern-ing [1]. Since DNA methylation is affected by the availability of the methyl groups, derangements in one carbon (methyl) metabolism and of methionine induced by nutritional and environmental perturbations can impact the expression of certain genes at vital moments during development.
Methionine, an essential amino acid, plays a critical role in the one-carbon metabolism in vivo. Methionine is metabolized first by the ubiquitous transmethylation (‘methionine’) cycle, wherein the methyl groups from methionine and from folate-dependent one-carbon pool participate in methyltransferase reactions [2]. The catabolic pathway of methionine involves the transsulfuration sequence, resulting in the synthesis of cysteine, which then participates in the formation of gluta-thione – a major intracellular antioxidant. Metabolism of methionine is regulated by nutrients, folate, cobalamine, pyridoxine, protein intake, and by insulin and glucagon.
Methionine metabolism has not been examined in detail during pregnancy and in the fetus. Data from studies in human pregnancy show a progressive decline in plasma homocysteine concentration dur-ing pregnancy and an increase in plasma choline concentration [3]. In addition, the umbilical arteriovenous concentration gradient suggests fetal uptake and utilization of homocysteine. Finally, it is significant to note that hepatic transsulfuration is not active in the human fetus and appears for the first time after birth. Preliminary data from our studies
26
in the rat, using the commonly employed model of intrauterine growth restriction, show that as a result of dietary protein restriction, major changes in the plasma amino acid pattern are accompanied by down-regulation of the methionine transsulfuration pathway [4]. Gene-array studies showed a marked increase in the pathway of serine synthesis. The impact of these changes on fetal growth and specific epigenetic changes remains to be determined.
In human adults, obesity and fatty liver disease are also accompa-nied by changes in methionine metabolism, resulting in a lower plasma concentration of glutathione and an increase in the plasma concentra-tion of homocysteine and cysteine. A significant correlation between insulin resistance and plasma glutathione and cysteine was observed. A significant association between MTHFR 677CT homozygosity, which may impact folate metabolism, and non alcoholic fatty liver dis-ease was observed [5].
Perturbations in methionine metabolism, as a result of nutrient/environment interactions early in life or as a result of hepatic dysfunc-tion in adult life, may play a key role in metabolic patterning during development and propagation of the disease process in adults.
References
1 Jones PA, Takai D: The role of DNA methylation in mammalian epigenetics. Science 2001;293:1068–1070.
2 Stipanuk MH: Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 2004;24:539–577.
3 Velzing-Aarts FC, Holm PI, Fokkema MR, et al: Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr 2005;81:1383–1389.
4 Kalhan SC, Parimi PS, Hanson RW: Impact of dietary protein restriction on one carbon metabolism in the rat. Pediatric Academic Societies Annual Meeting, 2006.
5 Edmison JM, Dasarathy S, Kalhan SC, McCullough AJ: Severity of non-alco-holic fatty liver disease is related to MTHFR 677CT homozygosity, lower glutathione and insulin resistance. Hepatology 2007;46:749A.
27
Adiposity and Comorbidities: Favorable Impact of Caloric Restriction
Eric Ravussin
The focus of my presentation will be on research involving long-term calorie restriction (CR) to prevent or delay the incidence of the metabolic syndrome with age. The current societal environment is marked by overabundant accessibility of food coupled with a strong trend to reduced physical activity, both leading to the development of a constellation of disorders including central obesity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome).
Prolonged CR has been shown to extend median and maximal lifespan in a variety of lower species (yeast, worms, fish, rats, and mice). Mechanisms of this lifespan extension by CR are not fully eluci-dated, but possibly involve alterations in energy metabolism, oxidative damage, insulin sensitivity, and functional changes in neuroendocrine systems. Ongoing studies of CR in humans now makes it possible to identify changes in ‘biomarkers of aging’ to unravel some of the mech-anisms of its anti-aging phenomenon.
Analyses from controlled human trials involving long-term CR will allow investigators to link observed alterations from body com-position down to changes in molecular pathways and gene expression, with their possible effects on the metabolic syndrome and aging.
A summary of the physiological and psychological/behavioral responses to 6 months of CR in humans from the Pennington CAL-ERIE randomized clinical trial are summarized in table 1.
28
Table 1.
Physiological responses Psychological/behavioral responses
Body composition Fat mass Fat-free mass Abdominal fat (visceral and
subcutaneous) Abdominal fat cell size Intra-hepatic lipid content Intra-myocellular lipid content
Development of eating disorder symptoms Disinhibition Binge eating Concern about body size and
shape Fear of fatness Purgative behavior
Diabetes risk factors Insulin sensitivity (not
significant) Acute insulin response to
glucose
Depressed mood MAEDS Depression scale Beck Depression Inventory II
Cardiovascular disease risk 10-year risk Blood pressure HDL-C Triacylglycerol Factor VIIc Fibrinogen, homocysteine,
endothelial function
Subjective feelings of hunger Eating Inventory, Perceived
Hunger Scale
Biomarkers of longevity Fasting insulin Core body temperature DHEA-S
Quality of life Physical functioning Vitality
Energy expenditure 24-hour sedentary energy
expenditure Metabolic adaptation for 24-hour
energy expenditure Sleeping metabolic rate (SMR) Metabolic adaptation for SMR
Cognitive performance Verbal memory Short-term memory and
retention Visual perception and memory Attention/concentration
Endocrinology T3 T4 GH IGF-1 Ghrelin
Physical activity Physical activity level (TDEE
adjusted for SMR) Spontaneous physical activity
29
Obesity, Inflammation, and Macrophages
Vidya Subramanian and Anthony W. Ferrante, Jr.
The incidence of obesity has dramatically increased worldwide and is associated with numerous clinical pathologies. Particularly con-cerning is the rapid increase in obesity and associated comorbidities in children. White adipose tissue not only stores excess calories as energy but is an active endocrine organ that regulates metabolic and immunological processes in the body. In recent years it has become clear that obesity is associated with chronic low grade inflammation that involves activation of inflammatory signaling pathways, increased production of cytokines and acute-phase proteins. This state of sys-temic inflammation is thought to be a common denominator for the development of many metabolic complications of obesity. The inflam-matory response in obesity seems to originate predominantly from adi-pose tissue though other organs like liver may also be involved during progression of the disease. In both obese humans and rodents, adipose tissue expression and secretion of numerous inflammatory cytokines and acute phase proteins including tumor necrosis factor-� (TNF-�), monocyte chemoattractant proteins (MCPs), interleukin-6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1) are significantly increased [1]. Studies show that elevated circulating concentrations of proin-flammatory factors predict the development of insulin resistance and other metabolic complications of obesity.
Adipose tissue is a heterogeneous organ consisting of adipocytes and the non-adipocyte stromal vascular cells. Numerous studies have shown an unexpected role for immune cells, particularly macrophages within the stromal vascular fraction of adipose tissue in the develop-ment and progression of systemic inflammation. Gene expression analyses revealed that most of the proinflammatory factors secreted by adipose tissue are predominantly expressed by macrophages in the adipose tissue [2]. Furthermore, in obesity not only is the number of macrophages increased but the character of macrophages from adipose tissue of obese subjects is more inflammatory. These macrophages are
30
Lean adipose tissue
Obese adipose tissue
Monocytes
Monocytes
Adipocytes
Adipocytes
ICAM-1/
VCAM
ICAM-1/
VCAM
Adipose tissue
macrophages
(ATM)
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macrophages
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IL-10
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IL-6
IL-10
Adiponectin
Resistin
Resistin
Adiponectin
End
oth
eliu
mE
nd
oth
eliu
m
a
b
Fig. 1. Adipose tissue macrophages in obesity-induced inflammation. a In lean animals the macrophage content is low in adipose tissue. These mac-rophages express low amounts of inflammatory factors including tumor necro-sis factor alpha (TNF-�), interleukin 6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1) and high levels of anti-inflammatory factors including inter-leukin-10 (IL-10). b Obesity increases monocyte adhesion and recruitment to adipose tissue consequently increasing macrophage number in adipose tissue. The macrophages in obese adipose tissue express increased amounts of inflammatory factors including TNF-�, IL-6, and PAI-1 and decreased amounts of IL-10. The inflammatory molecules act locally in a paracrine fashion to alter adipocyte function and adipokine production.
31
bone marrow derived and their number in adipose tissue is strongly correlated with body weight, body mass index and total body fat [3]. Macrophages actively recruited during weight gain are phenotypically different from resident adipose tissue macrophages. Resident mac-rophages in the adipose tissue of lean individuals produce relatively low levels of inflammatory molecules including TNF-�, PAI-1, and IL-6 (fig. 1a). In contrast, the recruited macrophages in adipose tissue express high levels of inflammatory molecules that contribute to sys-temic inflammation and insulin resistance (fig. 1b).
The recruitment of bone marrow-derived circulating monocytes to adipose tissue is a complex process under the control of various chemokines, cytokines, and other local factors [2]. In obesity, among the inflammatory molecules whose expression is increased is the MCPs family that binds a common receptor C-C chemokine receptor-2 (CCR2). CCR2 is expressed on circulating monocytes, and is important in many forms of inflammation that involve macrophage accumula-tion, including bacterial infections, autoimmune diseases and athero-sclerosis. In obese rodents, the genetic deletion or pharmacological antagonism of CCR2 decreases macrophage accumulation in adipose tissue and improves obesity induced inflammation and insulin resis-tance [3]. In obesity, adipocytes also increase secretion of factors that enhance the adhesion and transmigration of monocytes into adipose tissue as well as their survival. Macrophage colony-stimulating factor (CSF-1), a key factor for the proliferation, differentiation, and survival of monocytes and macrophages, is significantly increased in obese adi-pose tissue. Additionally, obesity-induced increase in adipocyte death secondary to hypertrophy is also thought to play a role in recruiting macrophages [4]. However, further studies are required to identify the exact signals that turn on macrophage recruitment and inflammation in obese adipose tissue.
Macrophage accumulation and adipose tissue inflammation are dynamic process under the control of multiple mechanisms. Interven-tions aimed at either reducing macrophage numbers or decreasing their inflammatory characteristics improve insulin sensitivity and decrease inflammation. Investigating the role of macrophages in adipose tissue biology and the mechanisms involved in their recruitment and activa-tion in obesity will provide useful insights for developing new thera-peutic options to treat obesity-induced complications.
References
1 Wellen KE, Hotamisligil GS: Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111–1119.
32
2 Charo IF, Ransohoff RM: The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354:610–621.
3 Weisberg SP, Hunter D, Huber R, et al: CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006;116:115–124.
4 Cinti S, Mitchell G, Barbatelli G, et al: Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005;46:2347–2355.
33
Obesity, Hepatic Metabolism and Disease
John M. Edmison, Satish C. Kalhan and Arthur J. McCullough
Nonalcoholic steatohepatitis (NASH), the most severe form of nonalcoholic fatty liver disease (NAFLD), is emerging as a common and clinically important type of chronic liver disease in industrialized countries. Rates are rapidly increasing in developing countries as well [1]. NAFLD and obesity should be regarded as a global health problem of increasing dimensions (table 1).
The prevalence of NAFLD and its most severe form, NASH, are estimated to be 30 and 7–8%, respectively, in the Western world [2] (table 2).
NASH is a progressive fibrotic disease in which cirrhosis and liver-related death occur in up to 20 and 12%, respectively, over a 10-year period [3]. NASH-associated cirrhosis can also decompensate into subacute liver failure, progress to hepatocellular carcinoma and recur post-transplantation. In contrast, steatosis alone has a more benign course [1, 3].
Table 1. Prevalence of obesity (%) in Asia using WHO criteria for Asians
Country Men Women
China 12 14Japan 24 20Malaysia 24 18Philippines 13 15Taiwan 18 16Thailand 17 20
34
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35
There is a strong link between NAFLD/NASH and the metabolic syndrome and, in particular, obesity. It should be emphasized that obesity (defined by BMI) differs between Western and Asian societ-ies, being >30 and >25, respectively. Assessment of central adiposity is extremely important in ‘lean’ people. Although there are a number of potential pharmacological therapies being developed, diet and exer-cise should be the initial options for the management.
Public health initiatives are imperative to halt or reverse the ‘diabesity’ epidemic, which is the underlying cause of NAFLD. A num-ber of important and unresolved issues must be clarified before the true epidemiology and natural history of NAFLD/NASH can be fully understood; this is particularly so in developing countries [4, 5].
References
1 McCullough AJ: The epidemiology and risk factors of NASH; in Fatty Liver Disease: NASH and Related Disorders. Oxford, Blackwell, 2005, pp 23–37.
2 Browning JD, Szczepaniak LS, Dobbins R, et al: Prevalence of hepatic steato-sis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.
3 Matteoni CA, Younossi ZM, Gramlich T, et al: Nonalcoholic fatty liver dis-ease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413–1419.
4 Vikram NK, Misra A, Pandey RM, et al: Heterogeneous phenotypes of insu-lin resistance and its implications for defining metabolic syndrome in Asian Indian adolescents. Atherosclerosis 2006;186:193–199.
5 Misra A, Misra R, Wijesuriya M, Banerjee D: The metabolic syndrome in South Asians: continuing escalation and possible solutions. Indian J Med Res 2007;125:345–354.
6 Ford ES: The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis 2004;173:309–314.
36
The Imperative of Preventive Measures Addressing Lifecycle
Chittaranjan S. Yajnik
The epidemiological characteristics of chronic non-communicable diseases (NCDs) are changing fast. The prevalence has risen to unprec-edented levels, and the young and the underprivileged are increasingly affected. The classic view of the etiology of NCDs consists of a genetic susceptibility which is precipitated by aging and modern lifestyle. In a virtual absence of any methods to tackle genetic susceptibility, the pre-ventive approach has so far focused on control of lifestyle factors in those at high risk (the elderly and those with a positive family history and elevated risk factors). Thus diet and physical activity modification have been claimed to ‘prevent diabetes’, while some trials have used pharmacological agents. Such an approach might help high risk indi-viduals but is unlikely to curtail the burgeoning epidemic of obesity and diabetes which is rapidly spreading to the young.
Recent research has suggested that susceptibility to NCDs origi-nates in early life through non-genetic mechanisms (fetal program-ming), and tackling these may offer a unique opportunity to curtail this epidemic. Size at birth and childhood growth characteristics are strong risk factors for NCDs. Both low and high birthweight and rapid child-hood growth (including early adiposity rebound) predict adult diabe-tes and related disorders. Children born small but having grown big have the highest levels of risk factors (fig. 1). This has led to the new paradigm of ‘Developmental Origins of Health and Disease’ (DOHaD), applicable to a number of conditions which make up the modern day NCD epidemic (diabetes, hypertension, coronary artery disease, can-cer, etc.). This new paradigm shifts our attention to the intrauterine and childhood environment, in addition to regulating lifestyle factors in adults. This philosophy is part of the ‘life course’ model of NCD (fig. 2). It is easy to appreciate the importance of the intrauterine period in the life cycle if we remember that over three fourths of cell divisions are over before we are born, and that a newborn human is almost a min-iature adult.
37
There has been intense research in humans and animal models of the factors which regulate growth and which might contribute to the DOHaD. The mechanisms involved in fetal programming are only beginning to be understood. Maternal nutrition and metabolism, and placental function are all involved. Periconceptional maternal nutri-tion (for example, vitamin B12 and folate) is an important determinant of not only neural tube growth but also of body composition and the metabolic characteristics of the offspring. Thus, there are windows of opportunity in the early life to improve the health of the individual. Research has also pointed towards genetic factors which affect growth
0.5
1
1.5
2
3 2 1 32
1
8-year weight
HOMA
resistance
Birthweight
Fetal
life
Infancy
and
childhood
Adolescence Adult life
Develo
pm
ent
of
NC
D
Accumulated
NCD risk
Age
1 3 42
Fig. 1. Insulin resistance. Source: Bavdekar et al. [5].
Fig. 2. The WHO life course model suggests that non-communicable dis-eases have their origins in early life. The risk progressively accumulates throughout the life course and disease manifests in later life. According to WHO/NMH/NPH 2001.
38
and disease susceptibility (fetal insulin hypothesis). The focus is likely to be on the environmental regulation of the expression of such genes during crucial phases of development (epigenetics). One such mecha-nism is methylation of regulatory portions of the genome which may be modified by the availability of methyl groups in the diet (nutritional programming), so elegantly shown in Agouti mice. Intergenerational transmission of such epigenetic changes explains some of the observa-tions on transmission of phenotypes which otherwise could be mis-taken for ‘genetic’ effects.
Thus, improving the early life environment offers a new and excit-ing opportunity to control the NCD epidemic by influencing the sus-ceptibility in a more durable manner than only controlling lifestyle factors in adult life. The imperative is to address the life cycle rather than concentrate on the end stages.
References
1 Barker DJP: Mothers, Babies and Health in Later Life. London, Churchill Livingstone, 1998.
2 Yajnik CS: Early life origins of insulin resistance and type 2 diabetes in India and other Asian countries. J Nutr 2004;134:205–210.
3 Yajnik CS, Deshpande SS, Jackson AA, et al: Vitamin B12 and folate concen-trations during pregnancy and insulin resistance in the offspring: The Pune Maternal Nutrition Study. Diabetologia 2008;51:29–38.
4 Eriksson JG, Forsén T, Tuomilehto J, et al: Early adiposity rebound in child-hood and risk of type 2 diabetes in adult life. Diabetologia 2003;46:190–194.
5 Bavdekar A, Yajnik CS, Fall CH, et al: Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 1999;48:2422–2429.
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New Approaches to Optimizing Early Diets
Staffan Polberger
The increasing number of surviving extremely preterm infants with gestational age of 23 weeks and birthweights from 400 g yields a new challenge to neonatal nutrition. The vast majority of extremely low birthweight (ELBW; <1,000 g) infants will survive if they are born and taken care of at a hospital with a tertiary neonatal intensive care unit. Preterm infants should be given optimal nutrition for brain growth and development. Nutrition during the vulnerable preterm period, prefer-ably based on human milk, leads to adequate growth, at least corre-sponding to the intrauterine growth rate.
In Sweden, an individualized feeding system has been developed during the last 10–15 years. Most ELBW infants are fed according to the scheme: (1) mother’s own milk (preferred); (2) banked milk (if mother’s milk is not available); (3) preterm infant formula (if human milk is not available), and (4) supplementary parenteral nutrition (starting at birth).
There is a trend to a more ‘aggressive’ nutrition of preterm infants, i.e. initiating nutrition early after birth including administration of not only intravenous glucose but also amino acids and lipids immediately after birth or during the first day of life. Enteral feeding, preferably with human milk, is also started during the first few hours of life.
There is growing evidence that human milk is superior to infant formula for all newborn infants including the ELBW infants. Human milk confers nutritional and non-nutritional advantages, and there is now a worldwide trend using more human milk for feeding of preterm infants than infant formula. Outcome data support improved neuro-logical development with human milk, even if the human milk intake has been limited to only a few weeks.
Unfortunately, but still in widespread use over the world, is the misconception that human milk has a predictable and uniform compo-sition. However, several studies have underlined the enormous varia-tion in the nutrient composition of human milk, particularly fat and to a less extent protein. There is a variation between mothers during the
40
course of lactation, during individual meals and also as a consequence of varying pumping techniques.
To account for this fact, a system with routine macronutrient anal-yses of the milk based on an infrared technique is used once a week, allowing optimal intakes of protein and energy. Analyses are always performed on 24-hour collections as spot samples cannot be used due to the enormous meal-to-meal-variation. Also, all banked milk is ana-lyzed, and the most protein-rich milk is chosen for a newborn ELBW infant.
To further reduce the variation in nutrient intake of ELBW infants, mother’s own milk is given in chronological order, i.e. in the order it was pumped. Also, all milk is mixed in 24-hour collections before being given or frozen. This will substantially reduce the day-to-day and meal-to-meal-variation in nutrient content, which is likely to increase the gut tolerance.
After a few weeks when the volumes cannot be further increased, the milk is fortified when a computerized calculation has shown that the protein and, secondly, energy intakes need to be further increased. Parenteral nutrition is discontinued when the enteral intake consti-tutes 75–80% of the total volume intake. The goal is to reach daily pro-tein and energy intakes of 3.5–4 g/kg and 110–120 kcal/kg, respectively. To further assess the metabolic capacity to utilize the protein given, markers, e.g. serum urea and transthyretin, are evaluated. Growth is monitored by regular measurements of weight, crown-heel length and head circumference, preferably by the same person each time, and for-tification is continued throughout the tube-feeding period until breast-feeding is initiated before discharge.
References
1 Ziegler EE: Breast-milk fortification. Acta Paediatr 2001;90:720–723.2 Heiman H, Schanler RJ: Enteral nutrition for premature infants: the role of
human milk. Semin Fetal Neonatal Med 2007;12:26–34.3 Michaelsen KF, Skafte L, Badsberg JH, Jørgensen M: Variation in macronutri-
ents in human bank milk: Influencing factors and implications for human milk banking. J Pediatr Gastroenterol Nutr 1990;11:229–239.
4 Polberger S, Räihä NCR, Juvonen P, et al: Individualized protein fortifica-tion of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier. J Pediatr Gastroenterol Nutr 1999;29:332–338.
5 Omarsdottir S, Casper C, Åkerman A, et al: Breast milk handling routines for preterm infants in Sweden: a national cross-sectional study. Breastfeed Med 2008, in press.
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Prevention of Low Birthweight
Dewan S. Alam
Globally an estimated 20 million or 15.5% of babies are born with low birthweight (LBW) defined as less than 2,500 g at birth with wide variations over different geographic locations [1]. However, over 90% of all LBW infants are born in developing countries and a half of the total global burden of LBW infants is distributed in South Central Asian countries. LBW may result from suboptimal fetal growth rela-tive to gestational age, called intrauterine growth retardation (IUGR) or small for gestational age (SGA), or too early delivery called preterm delivery (<37 weeks of gestation). The distinction of these two entities has important programmatic implications as the determinants are dif-ferent and so are the interventions.
LBW infants are at increased risk of mortality, morbidity, impaired growth and cognitive function, decreased motor and psychomotor development. In the longer term they are at increased risk of type 2 diabetes, hypertension, and cardiovascular disease [2]. These chronic diseases are emerging as epidemic in many developing countries. This high prevalence of non-communicable diseases in developing coun-tries is consistent with the very high prevalence of LBW. The economic cost of LBW is also enormous due to its immediate and long-term con-sequences on health and economic productivity [3].
Major determinants included low caloric intake during pregnancy or low gestational weight gain, low prepregnancy weight, short stat-ure, morbidity and cigarette smoking with different attributable risks for LBW in developed and developing countries [4]. In some settings, particularly in African countries where HIV and malaria coexist with maternal malnutrition HIV status, malaria and intestinal parasitic infestations are also important determinants. Micronutrient deficien-cies are also likely to influence birth outcome.
Major interventions aimed to prevent LBW include balanced energy protein supplementation, micronutrient supplementation, fish oil, treatment of infection, cessation of smoking, and social inter-ventions. The summary result of the systematic review of balanced
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protein-energy supplementation show a positive effect of supplement on birthweight (+32 g) and a one-third reduction in LBW but no effect on gestational age [5]. High protein supplementation during pregnancy is reported to be harmful.
Intervention with micronutrient supplementation includes either single or a combination or more recently a mix of 15 micronutrients recommended by UNICEF and WHO. Among single micronutrient supplementation trials only calcium and magnesium supplementa-tion during pregnancy was found to reduce LBW. A recent study in the United States reported that iron supplementation during preg-nancy in iron-replete women improved birthweight and reduced the incidence of LBW [6]. Results of multiple micronutrient supplementa-tion on birthweight and the incidence of LBW have been mixed. Some studies showed no additional benefits on birthweight over traditional iron folate supplementation, and some studies reported the superior efficacy of multiple micronutrients on birthweight and lowering the incidence of LBW [7–9]. Noticeably, the positive effect of multiple micronutrients shown in Nepal worked selectively on normal BMI women and female infants. One study reported multiple micronutri-ents to be associated with increased perinatal mortality [10].
While absolute prevention of LBW is unrealistic, bringing the incidence to a more acceptable level requires a very comprehensive approach based on the need and feasibility of combined interventions, as single interventions often showed either no or very little effect. There is no single strategy that seems to be universally applicable or efficacious. While IUGR seem to respond well to intervention, preterm delivery is more complex and resilient to intervention, and further investigation on the mechanistic aspect of this problem is required to identify effective interventions. The global epidemic of diabetes, car-diovascular diseases and hypertension which is linked to size at birth can only be effectively prevented with a healthy start to life by prevent-ing LBW.
References
1 United Nation Children’s Fund and World Health Organization: Low Birthweight: Country, Regional and Global Estimates. New York, UNICEF, 2004.
2 Barker DJ: The fetal origins of diseases of old age. Eur J Clin Nutr 1992;46(suppl 3):S3–S9.
3 Alderman H, Berhman JR: Reducing the incidence of low birth weight in low-income countries has substantial economic benefits. World Bank Res Observ 2006;21:25–48.
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4 Kramer MS: Intrauterine growth and gestational duration determinants. Pediatrics 1987;80:502–511.
5 Kramer MS: Balanced protein/energy supplementation in pregnancy. Cochrane Database Syst Rev 2001;3.
6 Cogswell ME, Parvanta I, Ickes L, et al: Iron supplementation during preg-nancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 2003;78:773–781.
7 Christian P, Khatry SK, Katz J, et al: Effects of alternative maternal micronutri-ent supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ 2003;326:571.
8 Osrin D, Vaidya A, Shrestha Y, et al: Effects of antenatal multiple micronutri-ent supplementation on birthweight and gestational duration in Nepal: dou-ble-blind, randomised controlled trial. Lancet 2005;365:955–962.
9 Ramakrishnan U, Gonzalez-Cossio T, Neufeld LM, et al: Multiple micronutri-ent supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation: a randomized controlled trial in a semirural community in Mexico. Am J Clin Nutr 2003;77:720–725.
10 Christian P, West KP, Khatry SK, et al: Effects of maternal micronutrient sup-plementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Am J Clin Nutr 2003;78:1194–1202.
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Community-Based Approaches to Address Childhood Undernutrition and Obesity in Developing Countries
Prakash Shetty
Community-based approaches have been the mainstay of inter-ventions to address the problem of child malnutrition in developing societies. The conceptual frameworks that have underpinned commu-nity-based approaches to improve child health and nutrition include the food-care-health triad and the triple A process [1] and the life cycle approach to undernutrition [2]. Many programs have been in opera-tion in several countries for decades and originated largely as social welfare, food security and poverty eradication programs, although the evaluation of the evidence of what intervention works and hence should be central to the community-based program is of more recent occurrence [3, 4]. Conceptual frameworks were developed to guide this activity as our understanding of the complex nature of the deter-minants of undernutrition and its links to the risk of overnutrition and chronic disease emerged. Alongside this evolution is the accumulation of the evidence of the types of interventions in the community that are effective, practical and also sustainable.
Critical evaluation of the evidence base of intervention studies in developing countries provides key insights [3, 4]. Strategies that aim to improve maternal nutrition and health appear to be the most sig-nificant interventions that have the best possible pregnancy outcomes. An adequate and diversified diet promotes weight gain in pregnancy and hence food supplements or balanced energy-protein supplementa-tion may be used to target vulnerable groups such as undernourished pregnant women and adolescent mothers. Multivitamin supplements have shown to be effective not only in improving maternal health and birth outcomes but also have an impact on subsequent infant growth and health. Promotion of exclusive breastfeeding for early infancy fol-lowed by optimum complementary feeding in the presence of good hygienic practices diminishes risk of infections, promotes infant
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growth and prevents child undernutrition. The success, effectiveness and the impact of large scale nutrition interventions, on the other hand, depend both on the contextual success factors, i.e. the macro-environ-ment in which the program operates, and the program success factors, i.e. the components, features and structure of the program itself [4, 5]. In addition the sustainability of the program depends on political will, availability of resources, both monetary and human, community par-ticipation and involvement and the level of institutionalization of the program that takes place over time.
The changing environment in developing societies with rapid developmental transition and urbanization is probably determining the changing scenario of child nutrition and is responsible for the emerging problems of obesity and other metabolic disorders in child-hood and in later adult life. This dramatic transition in developing societies is contributing to the double burden of malnutrition where the existing unfinished agenda of undernutrition is complicated and overwhelmed by the shift towards the emerging epidemic of obesity and increasing risk of chronic diseases. Community interventions hence need to be integrated and joined up to reduce both aspects of this malnutrition in societies and the interventions have to begin early in life. Because maternal and child undernutrition is the result of many factors, multiple sectors and strategies will have to bear on the objec-tive of eradicating this problem. Community-based approaches can work if established as broad-ranging, multi-sectored and integrated food and nutrition programs. With child undernutrition and obesity and adult chronic disease apparently linked, tackling the double bur-den of malnutrition is a priority. The evidence that community-based nutrition interventions can have a positive impact on this emerging problem needs to be evaluated to enable programs to prioritize and incorporate those interventions that work in the community. Com-munity-based approaches have to ensure a minimum package which addresses the ‘food-health-care’ triad of child malnutrition recogniz-ing the documented synergies in these approaches. Programs that are operational and successful need to be evaluated and disseminated in order to enable countries to generate their own programs tailored to tackle the changing nutritional problems of the children in their society.
References
1 UNICEF: Strategy for Improved Nutrition of Children and Women in Developing Countries. New York, UNICEF, 1990.
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2 Commission on the Nutrition Challenges of the 21st Century: Ending Malnutrition by 2020:An Agenda for Change in the Millennium. Geneva, UN Standing Committee on Nutrition, 2000.
3 Bhutta ZA, Darmstadt GL, Hasan BS, Haws RA: Community-based interven-tions for improving perinatal and neonatal health outcomes in developing countries: a review of the evidence. Pediatrics 2005;115(suppl):519–617.
4 Allen L, Gillespie S: What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions. Geneva, ACC/SCN; Manila, ADB, 2001.
5 FAO: Community-Based Food and Nutrition Programmes – What Makes Them Successful: A Review and Analysis of Experience. Rome, Food & Agriculture Organization, 2003.
List of Speakers
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Prof. Dewan Shamsul AlamPublic Health Sciences Division ICDDR,B68 Shaheed Tajuddin Ahmed SharaniMohakhali, Dhaka – 1212BangladeshE-Mail [email protected]
Prof. Parul ChristianDepartment of International HealthProgram in Human NutritionJohns Hopkins BloombergSchool of Public Health615 N. Wolfe Street, Rm E2541Baltimore, MD 21205USAE-Mail [email protected]
Prof. Satish C. KalhanDepartment of PathobiologyCleveland Clinic Lerner College of MedicineCase Western Reserve UniversityCleveland, OH 44195USAE-Mail [email protected]
Prof. Arthur McCulloughDepartment of Gastroenterology & HepatologyCleveland Clinic Lerner College of Medicine9500 Euclid Avenue, A-30Cleveland, OH 44195USAE-Mail [email protected]
Prof. Staffan PolbergerNeonatal Intensive Care UnitDepartment of PaediatricsUniversity HospitalSE–221 85 LundSwedenE-Mail [email protected]
Prof. B.M. PopkinInterdisciplinary Obesity CenterDepartment of Nutrition, School of Public HealthUniversity of North CarolinaCarolina Population Center123 West Franklin StreetChapel Hill, NC 27516-3997USAE-Mail [email protected]
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Prof. Andrew M. PrenticeMRC International Nutrition GroupLondon School of Hygiene and Tropical MedicineKeppel StreetLondon WC1E 7HT, UKE-Mail [email protected]
Prof. Marc-André ProstMRC International Nutrition GroupNutrition & Public Health InterventionResearch UnitEpidemiology and Population Health DepartmentLondon School of Hygiene & Tropical MedicineKeppel StreetLondon WC1E 7HTUK
Prof. Eric RavussinPennington Biomedical Research Center6400 Perkins RoadBaton Rouge, LA 70808USAE-Mail [email protected]
Prof. K. Srinath ReddyPublic Health Foundation of IndiaPHD House, Second Floor4/2, Sirifort Institutional AreaAugust Kranti Marg, New DelhiIndiaE-Mail [email protected]
Prof. Ana Lydia SawayaDepartment of PhysiologyFederal University of São PauloRua Botucatu 862, 2o andarSão Paulo, SPBrazilE-Mail [email protected]/[email protected]
Prof. Prakash ShettyInstitute of Human NutritionUniversity of SouthamptonMedical SchoolTremona RoadSouthampton SO16 6YDUKE-Mail [email protected]
Dr. Vidya SubramanianNaomi Berrie Diabetes CenterDepartment of MedicineColumbia University1150 St. Nicholas AvenueNew York, NY 10032USAE-Mail [email protected]
Prof. Emma WhitelawDivision of Population Studies and Human GeneticsQueensland Institute of Medical Research300 Herston RoadHerston, Brisbane 4006AustraliaE-Mail [email protected]
E-Mail [email protected]
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Prof. Chittaranjan S. YajnikKing Edward Memorial HospitalDiabetes UnitSardar Moodliar RoadPune 411011IndiaE-Mail [email protected]
Prof. Shi-an YinNational Institute for Nutrition and Food SafetyChinese Center for Disease Control and Prevention29 Nan Wei Road, Xuanwu DistrictBeijing 100050ChinaE-Mail [email protected]
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NOTA IMPORTANTE: AS GESTANTES E NUTRIZES PRECISAM SER INFORMADAS QUE O LEITE MATERNO É O IDEAL PARA O LACTENTE, CONSTITUINDO-SE A MELHOR NUTRIÇÃO E PROTEÇÃO PARA ESTAS CRIANÇAS. A MÃE DEVE SER ORIENTADA QUAN-TO À IMPORTÂNCIA DE UMA DIETA EQUILIBRADA NESTE PERÍODO E QUANTO À MANEIRA DE SE PREPARAR PARA O ALEITAMENTO AO SEIO ATÉ OS DOIS ANOS DE IDADE DA CRIANÇA OU MAIS. O USO DE MAMADEIRAS, BICOS E CHUPETAS DEVE SER DESENCORAJADO, POIS PODE TRAZER EFEITOS NEGATIVOS SOBRE O ALEITAMENTO NA-TURAL. A MÃE DEVE SER PREVENIDA QUANTO À DIFICULDADE DE VOLTAR À AMAMENTAR SEU FI-LHO UMA VEZ ABANDONADO O ALEITAMENTO AO SEIO. ANTES DE SER RECOMENDADO O USO DE UM SUBSTITUTO DO LEITE MATERNO, DEVEM SER CONSIDERADAS AS CIRCUNSTÂNCIAS FAMILIARES E O CUSTO ENVOLVIDO. A MÃE DEVE ESTAR CIENTE DAS IMPLICAÇÕES ECONÔMICAS E SOCIAIS DO NÃO ALEITAMENTO AO SEIO – PARA UM RECÉM-NASCIDO ALIMENTADO EXCLUSIVAMENTE COM MAMADEIRA SERÁ NECESSÁRIA MAIS DE UMA LATA POR SEMANA. DEVE-SE LEMBRAR À MÃE QUE O LEITE MATERNO NÃO É SOMENTE O MELHOR, MAS TAMBÉM O MAIS ECONÔMICO ALIMENTO PARA O LACTENTE. CASO VENHA A SER TOMADA A DECISÃO DE INTRODUZIR A ALIMENTAÇÃO POR MAMADEIRA É IMPORTANTE QUE SEJAM FORNECIDAS INSTRUÇÕES SOBRE OS MÉTODOS CORRETOS DE PREPARO COM HIGIENE RESSALTANDO-SE QUE O USO DE MAMADEIRA E ÁGUA NÃO FERVIDAS E DILUIÇÃO INCORRETA PO-DEM CAUSAR DOENÇAS. OMS – CÓDIGO INTERNA-CIONAL DE COMERCIALIZAÇÃO DE SUBSTITUTOS DO LEITE MATERNO. WHA 34:22, MAIO DE 1981. PORTARIA Nº 2.051 – MS, DE 08 DE NOVEMBRO DE 2001, RESOLUÇÃO Nº 222 – ANVISA – MS, DE 05 DE AGOSTO DE 2002 E LEI 11.265/06 – PRESIDÊNCIA DA REPÚBLICA, DE 04.01.2006 – REGULAMENTAM A CO-MERCIALIZAÇÃO DE ALIMENTOS PARA LACTENTES E CRIANÇAS DE PRIMEIRA INFÂNCIA E TAMBÉM A DE PRODUTOS DE PUERICULTURA CORRELATOS.
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Nestlé Nutrition Institute Workshop SeriesPediatric Program Volume 63
Emerging Societies -Coexistence ofChildhoodMalnutrition andObesity
Informação destinada exclusivamente ao profi ssional de saúdeImpresso no BrasilEO.OA/OL
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