I. SUMMARY OF THE PROBLEM
Obesity is considered a global epidemic because its prevalence and severity in both adults and children is increasing worldwide at alarming rates (1–7). This increase has been related to an increasingly sedentary lifestyle with less physical activity as well as changing dietary habits, and it occurs not only in affluent countries, but also in developing countries and in countries in economic transition (6,8–11). One consequence is that overweight and obesity are becoming the most prevalent childhood nutritional disorders in many parts of the world. As a result, more children experience severe psychosocial burdens and health risks, and because most obese children grow into obese adults, this trend is expected to lead to huge economic costs to health and social security systems. This review explores the causes, risks, and current approaches to prevention and treatment of childhood obesity, and potential research directions are discussed.
Body Mass Index (BMI) as a Measure for Overweight and Obesity
Obesity is an excessive deposition of fat in the body that is associated with adverse consequences for metabolic parameters, and short- and long-term physical health, as well as with significant psychosocial problems (1). Body fat mass can be estimated from using anthropometry with determinations of skinfold thickness values, or using technical measures such as bioelectrical impedance or dual-energy X-ray scans (12). In primary pediatric practice, overweight and obesity have traditionally been defined based on the basis of an excessive body weight relative to height. In adult medicine and increasingly in pediatrics, the body mass index (BMI; weight [kg]/height [m]2) tends to be accepted as the standard measure for overweight and obesity, because it tends to correlate better with body fat mass than relative weight (3), and it is relatively easy to determine. In adults, the generally accepted, although somewhat arbitrary, cutoff points are a BMI > 25 as the criterion for overweight, and a BMI of > 30 for the definition of obesity (1). In children and adolescents, BMI distribution varies markedly with age and gender, and age- and gender-specific reference standards are required. Different BMI distributions have been reported for various childhood populations studied. Recently, a standard definition for overweight and obesity in children worldwide has been proposed based on BMI centile curves that pass through the adult cutoff points of 25 and 30, respectively, at the age of 18 years (13). Using this standard and other measures, research showed that the prevalence of obesity varies widely between different childhood populations and appears to be influenced by genetic variation, seasonal and environmental factors, as well as regional traditions and cultural habits (13–15).
The BMI increases after birth until about 6 to 12 months of age, then decreases to a minimum in early childhood (usually at about 4 to 6 years). Thereafter, the BMI curves inflect and steadily increase and reach a plateau in young adulthood (13). The BMI rebound age, whicb is the age at when the BMI curve inflects, correlates closely with the risk of obesity in adulthood and is currently considered as the best predictor, during preschool age, of obesity risk in young adulthood (16,17).
The use of BMI measures for clinical purposes still raises some questions. In clinical practice, the calculation of a BMI value and the comparison with age- and gender-specific reference values may require more time and effort than the conventional use of weight-for-height centiles. The advantage of using BMI in pediatric clinical practice to identify the population at risk has not been conclusively demonstrated, however (18). Also, it remains to be elucidated whether one and the same set of BMI reference values is adequate to define the metabolic and health risks associated with overweight and obesity in all children.
Genetic and Other Biologic Factors Predisposing to Obesity
In relatively few children, obesity develops as a secondary consequence of other disorders, such as hypothyroidism, human growth hormone deficiency, Cushing syndrome, and hypothalamic lesions caused by intracranial tumor, trauma, or infection. Pediatricians are well aware of genetic defects leading to syndromatic obesity, such as those found in patients with Laurence Moon Bardet Biedl syndrome, Prader Willi syndrome, trisomy 21, Wiedemann Beckwith syndrome, and others. Recently, other specific, monogenetic disorders have been identified that are rare causes of hyperphagia and obesity beginning in early childhood. Among these identified single-gene defects are mutations in the leptin gene (19), the leptin receptor gene (20), the prohormone convertase-I gene (21), the pro-opio-melanocortin gene (22), and the melanocortin-4-receptor gene (23). Moreover, mutations affecting the activity of the peroxisomal proliferator activated receptor γ (PPARγ), which regulates the differentiation of adipocytes, have been associated with an increased body fat mass (24).
Syndromatic and monogenetic forms of obesity are not the only forms linked to genetic factors. In the general population, genetic factors play a role in the risk for development of obesity. In an investigation of 540 adults that had been adopted during childhood, no relationship between body weight centiles of adoptees and those of their adoptive parents was found. In contrast, the body weigth centiles of the adoptees did closely correlate with those of their biologic parents, from whom they had been separated since early childhood (25). To better understand the underlying pathophysiologic mechanisms, ongoing studies aim to identify genetic markers associated with obesity risk.
Early Metabolic Imprinting
In addition to genetic predisposition, metabolic programming (26) or metabolic imprinting (27) may also play a role in the risk of developing obesity: environmental factors that affect the organism during specific, critical periods of early development modulate the windows exogenous factors during early life appear to modulate the risk of obesity later. One study focused on a cohort study of 19-year-old men who had been exposed, in the prenatal or postnatal period, to the Dutch famine of 1944–45. Maternal exposure to famine during the last trimester of pregnancy and the first months of life was related to lower obesity prevalence rates, but exposure during the first half of pregnancy was associated with a higher obesity prevalence than in nonexposed controls (28). A later follow-up study of women and men aged 50 years, who were either exposed or not exposed to famine in late, mid, or early gestation, reported a higher BMI in exposed than in nonexposed women. However, there was no significant difference in men (29). Another study reported a higher risk of later obesity for children of Pima women with diabetes during pregnancy than for children of mothers who did not suffer from gestational diabetes. This difference persisted after correction for other influencing factors (30). These findings suggest that metabolic perturbations of regulatory systems established in early gestation contribute to the development of obesity in later life.
Postnatal feeding also appears to modulate the later risk of overweight and obesity. In a cross-sectional survey of 9,357 children entering school, BMI measurements were related to early feeding, diet, and lifestyle factors (31). The prevalence of obesity in children who had never been breast-fed was 1.6-fold higher than in previously breast-fed children. A clear dose–response effect of the duration of breast-feeding on the prevalence of later obesity emerged from this study. The protective effect of breast-feeding was not attributable to differences in social class or lifestyle. After adjustment for potential confounding factors, the study found that breast-feeding remained a protective factor against the development of overweight and obesity. Thus, in industrialized countries, promoting prolonged breast-feeding may help decrease the prevalence of obesity in childhood. The potential underlying mechanisms of this phenomenon remain to be elucidated. Together, these findings indicate that, in addition to genetic disposition, environmental factors strongly influence the risk of obesity development.
Current Lifestyle, Energy Balance, and Obesity Risk
Obesity is the consequence of an overall positive energy balance maintained over time, that is, the metabolizable energy intake exceeds the energy expenditure for basal metabolic requirements, thermoregulation, thermogenetic effects of feeding, physical activity, and growth (32). Several studies related basal energy expenditure to the metabolically active lean body mass and found no basal energy expenditure difference between obese children and children of normal weight (33–35). However, meal-induced thermogenesis may be slightly smaller in obese than in normal weight children (36,37). Thus, the major determinants of obesity development are energy expenditure induced by physical activity and energy intake from foods.
The degree of a person's physical activity markedly affects total energy expenditure and thus energy balance. Low physical activity levels are associated with obesity in children and adolescents and may be both cause and consequence of overweight (38–40). In addition to the direct effect of increasing energy expenditure, high physical activity also enhances muscle mass and thereby resting energy expenditure and muscular fat oxidation (41,42). The physical activity level of children is related to socioeconomic status and living conditions, peer pressure, and the degree of physical activity of their parents (43–45). As a consequence of an increasingly sedentary lifestyle, the level of physical activity of children and adolescents has declined in some countries during the past few decades (46–48). In some studies, the obesity risk of a child has been correlated to time spent viewing television, that is, times with a low level of physical activity and low energy expenditure (49–51). The apparent influence of such times on obesity risk might reflect combined effects of physical inactivity, snacking behavior, and specific personality and socioeconomic factors.
Diet and Obesity Risk
Dietary habits and food preferences, caloric content of the diet, and nutrient composition all appear to modulate the risk of obesity development. Dietary habits of children and adolescents are influenced by parents and other household members, peers, advertisements and media, the social context of eating, and possibly early feeding experience in infancy and genetic variation in taste preferences. However, the complexity of factors that influence food and feeding choices in children and adolescents is not well understood (52,53).
Theoretically, a relatively small excess of energy supplied would suffice to induce obesity, if maintained over a long period. The caloric content of 1 kg of body fat tissue is approximately 7,500 kcal (1.79 MJ) (whereas 1 kg fat equals 9,000 kcal). Thus, the deposition of 1 kg of additional adipose tissue over a period of 1 year would only require an average maintained energy excess of no more than 20.5 kcal/day or 2.3 g fat/day. In practice, however, the relationship is more complex because adaptive physiologic mechanisms on energy expenditure and feeding behavior modulate the effects of energy imbalances (54).
Because total energy intake is related to the energy density of the diet (55), diets with a high energy density (high energy content per food portion) are associated with a greater body fat deposition (53,56–60). The energy density of foods tends to correlate positively with fat contents and inversely with contents of complex carbohydrates, dietary fiber, and water. Moreover, each of the three major macronutrients proteins, carbohydrates, and fats has different effects on body weight gain. The body stores only limited amounts of excess proteins and carbohydrates, and high intakes of proteins and carbohydrates induce an enhanced oxidation of these two substrates (61). Only a small amount of carbohydrates is converted to fats in humans (62). Although human tissues have the general ability to synthesize fats from carbohydrates, net fat synthesis occurs only under extreme conditions after prolonged supplies of very high carbohydrate intake (63). However, the consumption of carbohydrates together with fats in excess of energy requirements can markedly influence body fat content because carbohydrates supplied in appreciable amounts suppress fat oxidation and thereby further enhance body fat deposition (64).
In contrast to carbohydrates and proteins, fats can be stored in the body in almost unlimited amounts, and an enhanced fat intake does not induce fat oxidation (61). Fat consumption induces very little thermogenetic effects compared with carbohydrates and proteins (65). Furthermore, at the same caloric intake, dietary fat has less satiating effects than protein or carbohydrates (66). Dietary fats also tend to carry flavors and have positive effects on mouthfeel as well as other organoleptic properties. These considerations may explain why obese children tend to consume a higher proportion of dietary energy as fat than children with normal weight (67). In adolescents, body fat content is positively related to dietary fat intake but inversely to dietary carbohydrate intake (both expressed as percentage of energy intake) (68). In conclusion, the percentage content of fat in the diet and the ratio of fat to the other macronutrients appear to be relevant modulators of body fat deposition.
In addition to the quantity, the quality of dietary fats also may be of relevance for obesity development, because fatty acids of different chain lengths and degree of unsaturation vary with respect to their oxidation (69,70). Studies in animals suggest that conjugated linoleic acids (CLA), which originate from ruminant fats, may inhibit fat deposition (71,72), but there is no conclusive evidence of similar effects in humans.
It has also been proposed that dietary protein intake may modulate body fat content. The percentage of body fat in rats increases if they consume an increasing proportion of protein (73). A high protein intake in excess of metabolic requirements may enhance the secretion of insulin and insulin-like growth factor 1 (IGF-1), which can stimulate adipogenic activity and adipocyte differentiation (74). In observational studies, the BMI rebound age and later BMI has been correlated to protein intake during early childhood (75), but such a relationship has not been confirmed in another prospective cohort study (76,77). More studies are required to further elucidate the potential role of protein intake.
Other Causative Factors
The contributions of psychosocial, socioeconomic, and behavioral factors to the development of obesity are complex and only partly understood at present, and considerable differences exist between different populations. In some but not all studies in affluent countries, low socioeconomic status is associated with higher rates of childhood obesity (31,78–80). Variables associated with low socioeconomic status, such as poor housing conditions, were also significantly related to obesity risk, even after the studies were corrected for parental education and job level (81).
Consequences of Obesity in Childhood and Adolescence
Childhood obesity has short- and medium-term medical and psychosocial consequences in childhood and adolescence, as well as long-term effects that extend well into adulthood (80). Obese children often experience psychosocial distress and, in many cultures, considerable discrimination. Obese adolescents are at a clear disadvantage with respect to completion of advanced education, household income achieved in adulthood, and rates of marriage (82,83). Longitudinal growth is enhanced in overweight and obese children, and they experience earlier maturation and advanced bone ages (84). The resulting above average height, together with other aspects of different body appearance, such as pseudohypogenitalism in boys, may have pronounced psychological consequences and affect self-esteem (85).
Obesity during childhood and adolescence affects the cardiovascular risk factors dyslipidemia, glucose intolerance, arterial hypertension, and antioxidant vitamin status. Dyslipidemia, with increased concentrations of plasma triglycerides and low-density lipoportein (LDL) cholesterol, and reduced high-density lipoportein (HDL) cholesterol concentrations, is a common finding (80,86). The cardiovascular consequences of dyslipidemia may be aggravated by an accompanying depletion of antioxidants such as vitamin E (87,88). Obesity induces reduced insulin sensitivity, pathologic glucose tolerance, and increased fasting and postprandial blood glucose concentrations, and it plays a key role in the marked increase of non–insulin-dependant diabetes mellitus recently observed in some pediatric populations (89). Increased insulin resistance may disturb the metabolism of essential polyunsaturated fatty acids and therefore may influence membrane properties, eicosanoid metabolism, and functions of the cardiovascular system (90,91). In addition to BMI or body fat mass, the distribution of body fat modulates lipoprotein metabolism as well as overall adverse health consequences. Gluteofemoral body fat distribution, which is more prevalent in females from puberty onward, is associated with lower metabolic and cardiovascular risks than the abdominal fat deposition that is more frequently found in males (92–94). Other consequences of early obesity are nonalcoholic steatohepatitis, which sometimes results in cirrhosis (95,96), cholelithiasis, pseudotumor cerebri, sleep apnea that may be associated with neurocognitive deficits, disorders of the musculoskeletal system, and orthopedic complications with an increased long-term risk for arthrosis (80).
Persistence of childhood obesity into adulthood is common. It has been estimated that up to two thirds of all obese children become obese adults (97,98,99). The risk of persistent obesity increases in correlation with increasing age of the child, degree of obesity, and presence of parental obesity (C). Persistent obesity during adult life is associated with increased morbidity and mortality (100,101). Even independent of the effects of adolescent obesity on adult BMI, obesity in adolescence increased morbidity risk in adulthood (102,103)
The metabolic consequences and health risks associated with obesity cannot be explained by BMI alone. Rather, the relative health risk associated with particular BMI values appears to differ among populations in Western countries (104). Some studies have suggested that differences exist among populations of various ethnic origins with respect to the relative risks for type 2 diabetes mellitus and cardiovascular disease that are associated with high BMI values (105,106). Also, children born with a lower birthweight have a higher risk for insulin resistance at the same BMI than children born heavier (107). Thus, further characterization of metabolic and health risks associated with high BMI values in different childhood populations throughout the world is required.
Treatment and Prevention of Overweight and Obesity in Children and Adolescents
Obesity treatment should aim at long-term stabilization of body weight and body fat content within the normal range. Treatment should also take into consideration good quality of life, psychosocial and physical well-being, and the possibility of adverse effects of treatment. Most of the available treatment options focus on modification of dietary habits and composition, enhancement of physical activity, and other behavior changes. Long-term success of current obesity treatment programs over 5 to 10 years is not fully satisfactory, although long-term success appears to be better in the pediatric age-group than in adults (108). Compared with that for adults, obesity treatment has a greater effect for children because behavoir is less fixed and hence easier to modify in children and adolescents than adults. Other factors in the greater effect of childhood obesity treatment include greater support from family members and longitudinal growth and increase of lean body mass with age. Treatment of obesity in childhood most likely offers greater health preventive effects in view of the longer life expectancy (109). Thus, more efforts should be invested into further development and evaluation of treatment programs for overweight and obese children and adolescents.
The long-term success of dietary restrictions alone has been questioned (110). Very strict dietary limitations do not appear to have better long-term success than moderate dietary modifications (111). Moreover, these strict diets usually cannot be maintained for long periods, and considerable rebound effect is observed after they are discontinued (112). Very restrictive diets also carry the risk of adversely affecting growth risk because they may fail to meet basic nutrient requirements (110). Restrictive dietary recommendations might also increase the risk for later disturbances of eating patterns, eating disorders, and other adverse psychological effects (113,114). A combination of dietary intervention with exercise programs has better outcomes than either component alone. Combining the two enhances weight loss and better maintains weight changes (115–118). More study is needed to determine the types of exercise programs that would be most appropriate for use in obese children and adolescents.
Surgical interventions and drug treatments are not recommended for use in children and adolescents with common forms of obesity, because these treatments have not been sufficiently documented to be safe and effective in children and adolescents (108). However, future developments are likely to confer new options for useful pharmacologic treatment aids in young patients.
Behavioral and psychological forms of therapy that help to enhance physical activity and healthy eating habits, stabilize and reinforce health-promoting behavior, and strengthen-self confidence and independence are considered critical for the long-term success of treatment in obese children and adolescents (117,118). Simple measures, such as reducing children's television, videotape, and video game use, can contribute to decreasing overweight in children (119). Parental involvement in the child's behavioral treatment program has been shown to improve outcome after 1 year (108). A large variety of approaches exist with respect to behavioral treatment, and the choices of methods, types of programs, times and intensity of intervention, and degree of individualization of treatment need to be studied further.
Ambulatory treatment forms the basis of most intervention programs for obese children and adolescents. Stationary treatment in obesity camps, hospitals, or rehabilitation centers also has been used to a more limited extent (2,120). However, the cost–benefit ratios of group camps or inpatient therapy relative to outpatient treatment, in the absence or presence of specific complicating factors, have not been adequately evaluated.
Despite intensive efforts and considerable costs, most current obesity treatment programs enjoy limited success. Thus, approaches to effective primary prevention methods are particularly attractive and important. However, the appropriate measures, times of intervention, and selection of target populations that would translate into effective long-term prevention with adequate cost–benefit ratios and without adverse effects are unclear. More research is required in this area, along with further advances in understanding of underlying pathophysiologic mechanisms.
II. MAJOR ISSUES IN NEED OF INVESTIGATION OR IMPLEMENTATION
A number of areas require more research to improve our ability to prevent and treat obesity in children and adolescents. Priorities for further research include:
* Better characterization of the relevant genes and gene mutations involved in the regulation of body weight and body composition, the occurrence and severity of obesity, as well as characterization of the relevant gene products, the regulation of gene expression, and modulating effects of diet, physical activity, and other environmental factors.
* Better characterization of the role of environmental factors in the development of obesity, including the investigation of early programming of later obesity risk, potential critical and sensitive age periods for early programming, and the underlying mechanisms.
* Improvement of early identification of children at risk for obesity, and of the assessment of obesity severity and its associated risks. Better characterization among different age-groups and different populations of the relationship of BMI, or other measures of obesity, to metabolic complications such as dyslipidemia and glucose intolerance, and indicators of disease risk.
* Further delineation of the psychological and social consequences of overweight and obesity under different personal and environmental circumstances.
* Investigation of the development of physical activity and sedentary lifestyle patterns in childhood and adolescents and of approaches to modifications.
* Further characterization of the role of physical activity on energy metabolism, and metabolic activity of specific tissues on the regulation of regulation of appetite and food intake, and on dietary intake of energy and specific substrates.
* Research into the development of food habits, food patterns, and dietary choices in children and adolescents.
* Investigation of short- and long-term effects of dietary composition, energy density, macronutrient and micronutrient composition, and other components on food intake, energy balance, and body composition in children and adolescents.
* Further refinement and evaluation of programs for prevention and treatment of overweight and obesity in children and adolescents, including school- and community-based programs.
* Improvement and evaluation of programs for the further training of pediatricians and other health care workers, and enhancing awareness and competence among parents, teachers, and the general public.
III. PROPOSED PLANS TO ACHIEVE GOALS
Prevention of childhood obesity is an important goal, but our knowledge of the causes, modifiable risk factors, and effective forms of prevention and treatment of childhood obesity is still limited. In view of the major short- and long-term consequences of childhood obesity on health, well-being, and costs to health care and social security systems, as well as the better chances for intervention at young ages, public and private funding agencies should give a high priority to research on obesity in children and adolescents. Health care systems, as well as public and governmental institutions, should give the fight against obesity in children and adolescents a high priority. Practicing pediatricians and other health care workers with responsibility for children need to be further trained to enhance their awareness on overweight and obesity in childhood and adolescence, and to improve their competence in prevention and treatment. In addition, parents and the public at large need to be better informed about the problem and the possible contributions they can make to improve the health of children.
The authors thank Dr. William H. Dietz, Centers for Disease Control, Atlanta, USA, for fruitful discussions and constructive contributions. The writing of this paper was kindly supported in part by the charitable Child Health Foundation, Munich, Germany (http://www.kindergesundheit.de).
1. World Health Organisation. Obesity. Preventing and managing the global epidemic. Report of a WHO consultation on obesity.
Geneva: World Health Organisation; 1998.
2. Barth N, Ziegler A, Himmelmann GW, et al. Significant weight gains in a clinical sample of obese children and adolescents between 1985 and 1995. Int J Obes Relat Metab Disord 1997; 21( 2):122–6.
3. Troiano RP, Flegal KM. Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics 1998; 101:497–504.
4. Kopelman PG. Obesity as a medical problem. Nature 2000; 404( 6778):635–43.
5. Cernerud L. Height and body mass index of seven-year-old Stockholm schoolchildren from 1940 to 1990 Acta Paediatr 1993; 82( 3):304–5.
6. Popkin BM, Doak CM. The obesity epidemic is a worldwide phenomenon. Nutr Rev 1998; 56(4 Pt 1):106–14.
7. Freedman DS, Srinivasan SR, Valdez RA, et al. Secular increases in relative weight and adiposity among children over two decades: the Bogalusa Heart Study. Pediatrics 1997; 99( 3):420–6.
8. Popkin BM. The nutrition transition and its health implications in lower-income countries. Public Health Nutr 1998; 1( 1):5–21.
9. Drewnowski A, Popkin BM. The nutrition transition: new trends in the global diet. Nutr Rev 1997; 55( 2):31–43.
10. Schroeder DG, Martorell R, Flores R. Infant and child growth and fatness and fat distribution in Guatemalan adults. Am J Epidemiol 1999; 149( 2):177–85.
11. Martorell R, Khan LK, Hughes ML, et al. Obesity in women from developing countries. Eur J Clin Nutr 2000; 54( 3):247–52.
12. Brodie DA, Stewart AD. Body composition measurement: a hierarchy of methods. J Pediatr Endocrinol Metab 1999; 12( 6):801–16.
13. Cole TJ, Bellizzi MC, Flegal KM, et al. Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000; 320:1240–3.
14. Leung SS, Cole TJ, Tse LY, et al. Body mass index reference curves for Chinese children. Ann Hum Biol 1998; 25( 2):169–74.
15. Dietz-WH J, Gortmaker SL. Factors within the physical environment associated with childhood obesity. Am J Clin Nutr 1984; 39( 4):619–24.
16. Rolland CM, Deheeger M, Bellisle F, et al. Adiposity rebound in children: a simple indicator for predicting obesity. Am J Clin Nutr 1984; 39( 1):129–35.
17. Whitaker RC, Pepe MS, Wright JA, et al. Early adiposity rebound and the risk of adult obesity. Pediatrics 1998; 101( 3):E5.
18. Poskitt EM. Defining childhood obesity: the relative body mass index (BMI). European Childhood Obesity group. Acta Paediatr 1995; 84( 8):961–3.
19. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387( 6636):903–8.
20. Clement K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction [see comments]. Nature 1998; 392( 6674):398–401.
21. Jackson RS, Creemers JW, Ohagi S, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene [see comments]. Nat Genet 1997; 16( 3):303–6.
22. Durchschlag H, Biedermann G, Eggerer H. Large-scale purification and some properties of malate synthase from baker's yeast. Eur J Biochem 1981; 114( 2):255–62.
23. Vaisse C, Clement K, Guy GB, et al. A frameshift mutation in human MC4R is associated with a dominant form of obesity [letter]. Nat Genet 1998; 20( 2):113–4.
24. Ristow M, Muller WD, Pfeiffer A, et al. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 1998; 339( 14):953–9.
25. Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med 1986; 314( 4):193–8.
26. Barker DJ. In utero programming of chronic disease. Clin Sci Colch 1998; 95( 2):115–28.
27. Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr 1999; 69( 2):179–97.
28. Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy N Engl J Med 1976; 295( 7):349–53.
29. Ravelli AC, van-Der MJ, Osmond C, et al. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 1999; 70( 5):811–6.
30. Pettitt DJ, Baird HR, Aleck KA, et al. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983; 308( 5):242–5.
31. von Kries R., Koletzko B, Sauerwald T, et al. Breast feeding and obesity: cross sectional study. BMJ 1999; 319( 7203):147–50.
32. Rosenbaum M, Leibel RL, Hirsch J. Obesity [see comments] [published erratum appears in N Engl J Med 1998 Feb 19;338(3):555]. N Engl J Med 1997; 337( 6):396–407.
33. Sothern MS, Loftin M, Suskind RM, et al. The impact of significant weight loss on resting energy expenditure in obese youth. J Invest Med 1999; 47( 5):222–6.
34. Schutz Y, Rueda MC, Zaffanello M, et al. Whole-body protein turnover and resting energy expenditure in obese, prepubertal children. Am J Clin Nutr 1999; 69( 5):857–62.
35. Goran MI, Shewchuk R, Gower BA, et al. Longitudinal changes in fatness in white children: no effect of childhood energy expenditure [see comments]. Am J Clin Nutr 1998; 67( 2):309–16.
36. Maffeis C, Schutz Y, Zoccante L, et al. Meal-induced thermogenesis in lean and obese prepubertal children Am J Clin Nutr 1993; 57( 4):481–5.
37. Molnar D, Varga P, Rubecz I, et al. Food-induced thermogenesis in obese children. Eur J Pediatr 1985; 144( 1):27–31.
38. Klesges RC, Klesges LM, Eck LH, et al. A longitudinal analysis of accelerated weight gain in preschool children [see comments]. Pediatrics 1995; 95( 1):126–30.
39. Moore LL, Nguyen US, Rothman KJ, et al. Preschool physical activity level and change in body fatness in young children. The Framingham Children's Study. Am J Epidemiol 1995; 142( 9):982–8.
40. Maffeis C, Talamini G, Tato L. Influence of diet, physical activity and parents' obesity on children's adiposity: a four-year longitudinal study. Int J Obes Relat Metab Disord 1998; 22( 8):758–64.
41. Goldberg GR, Prentice AM, Davies HL, et al. Residual effect of graded levels of exercise on metabolic rate. Eur J Clin Nutr 1990; 44( 2):99–105.
42. Bingham SA, Goldberg GR, Coward WA, et al. The effect of exercise and improved physical fitness on basal metabolic rate. Br J Nutr 1989; 61( 2):155–73.
43. Johnson WG, Hinkle LK, Carr RE, et al. Dietary and exercise interventions for juvenile obesity: long-term effect of behavioral and public health models. Obes Res 1997; 5( 3):257–61.
44. Terre L, Drabman RS, Meydrech EF. Relationships among children's health-related behaviors: a multivariate, developmental perspective. Prev Med 1990; 19( 2):134–46.
45. Perusse L, Tremblay A, Leblanc C, et al. Genetic and environmental influences on level of habitual physical activity and exercise participation. Am J Epidemiol 1989; 129( 5):1012–22.
46. Hillman M, Adams J, Whitelegg J. One false move.
London: Institute for Policy Studies, 1990.
47. Durnin JV, Lonergan ME, Good J, et al. A cross-sectional nutritional and anthropometric study, with an interval of 7 years, on 611 young adolescent schoolchildren. Br J Nutr 1974; 32:169–79.
48. Harsha DW. The benefits of physical activity in childhood. Am J Med Sci 1995; 310(Suppl 1):S109–13.
49. Dietz-WH J, Gortmaker SL. Do we fatten our children at the television set? Obesity and television viewing in children and adolescents. Pediatrics 1985; 75( 5):807–12.
50. Deheeger M, Rolland CM, Fontvieille AM. Physical activity and body composition in 10 year old French children: linkages with nutritional intake? Int J Obes Relat Metab Disord 1997; 21( 5):372–9.
51. Klesges RC, Shelton ML, Klesges LM. Effects of television on metabolic rate: potential implications for childhood obesity. Pediatrics 1993; 91( 2):281–6.
52. Klesges RC, Stein RJ, Eck LH, et al. Parental influence on food selection in young children and its relationships to childhood obesity [published erratum appears in Am J Clin Nutr 1991 Dec;54(6):iv]. Am J Clin Nutr 1991; 53( 4):859–64.
53. Birch LL, Fisher JO. Development of eating behaviors among children and adolescents. Pediatrics 1998; 101( 539):549
54. Rosenbaum M, Leibel RL. The physiology of body weight regulation: relevance to the etiology of obesity in children. Pediatrics 1998; 101:525–39.
55. Koletzko B. Response to and range of acceptable fat intakes in infants and children. Eur J Clin Nutr 1999; 53(Suppl 1):S78–S83.
56. Michaelsen KF, Jorgensen MH. Dietary fat content and energy density during infancy and childhood: the effect on energy intake and growth. Eur J Clin Nutr 1995; 49( 7):467–83.
57. McCrory MA, Fuss PJ, Saltzman E, et al. Dietary determinants of energy intake and weight regulation in healthy adults. J Nutr 2000; 130(2S Suppl):276S–9S.
58. Rolls BJ. The role of energy density in the overconsumption of fat. J Nutr 2000; 130(2S Suppl):268S–71S.
59. Cox DN, Mela DJ. Determination of energy density of freely selected diets: methodological issues and implications. Int J Obes Relat Metab Disord 2000; 24( 1):49–54.
60. Prentice AM. Manipulation of dietary fat and energy density and subsequent effects on substrate flux and food intake. Am J Clin Nutr 1998; 67(3 Suppl):535S–41S.
61. Flatt JP. Use and storage of carbohydrate and fat. Am J Clin Nutr 1995; 61(4 Suppl):952S–9S.
62. Hellerstein M. De novo lipogenesis in humans: metabolic and regulatory aspects. Eur J Clin Nutr 1999; 53:S53–S65
63. Acheson KJ, Schutz Y, Bessard T, et al. Carbohydrate metabolism and de novo lipogenesis in human obesity Am J Clin Nutr 1987; 45( 1):78–85.
64. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty acid-cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; 1:785–9.
65. Jequier E, Schutz Y. Energy expenditure in obesity and diabetes. Diabetes Metab Rev 1988; 4( 6):583–93.
66. Blundell JE, Stubbs RJ. High and low carbohydrate and fat intakes: limits imposed by appetite and palatability and their implications for energy balance. Eur J Clin Nutr
1999;53 Suppl 1:S148–65.
67. Tucker LA, Seljaas GT, Hager RL. Body fat percentage of children varies according to their diet composition. J Am Diet.Assoc 1997; 97( 9):981–6.
68. Ortega AR, Andres CP, Requejo MA, et al. [The food habits and energy and nutrient intake in overweight adolescents compared to those with normal weight]. An Esp Pediatr 1996; 44( 3):203–8.
69. Papamandjaris AA, MacDougall DE, Jones PJ. Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications. Life Sci 1998; 62( 14):1203–15.
70. Jones PJ, Ridgen JE, Phang PT, et al. Influence of dietary fat polyunsaturated to saturated ratio on energy substrate utilization in obesity. Metabolism 1992; 41( 4):396–401.
71. West DB, Delany JP, Camet PM, et al. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol 1998; 275(3 Pt 2):R667–72.
72. Park Y, Albright KJ, Liu W, et al. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997; 32( 8):853–8.
73. Kim SH, Mauron J, Gleason R, et al. Selection of carbohydrate to protein ratio and correlations with weight gain and body fat in rats allowed three dietary choices. Int J Vitam Nutr Res 1991; 61( 2):166–79.
74. Hauner H, Wabitsch M, Zwiauer K, et al. Adipogenic activity in sera from obese children before and after weight reduction. Am J Clin Nutr 1989; 50( 1):63–7.
75. Rolland CM, Deheeger M, Akrout M, et al. Influence of macronutrients on adiposity development: a follow up study of nutrition and growth from 10 months to 8 years of age. Int J Obes Relat Metab Disord 1995; 19( 8):573–8.
76. Dorosty AR, Emmett PM, Cowin IS, et al. Factors associated with early adiposity rebound. Pediatrics 2000; 105:1115–8.
77. Parizkova J, Rolland CM. High proteins early in life as a predisposition for later obesity and further health risks [editorial]. Nutrition 1997; 13( 9):818–9.
78. Lissau I, Sorensen TI. Parental neglect during childhood and increased risk of obesity in young adulthood. Lancet 1994; 343( 8893):324–7.
79. Kromeyer K, Hauspie RC, Susanne C. Socioeconomic factors and growth during childhood and early adolescence in Jena children. Ann Hum Biol 1997; 24( 4):343–53.
80. Dietz WH. Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 1998; 101:518–25.
81. Lissau-Lund SI, Sorensen TI. Prospective study of the influence of social factors in childhood on risk of overweight in young adulthood. Int J Obes Relat Metab Disord 1992; 16( 3):169–75.
82. Gortmaker SL, Must A, Perrin JM, et al. Social and economic consequences of overweight in adolescence and young adulthood [see comments]. N Engl J Med 1993; 329( 14):1008–12.
83. Sargent JD, Blanchflower DG. Obesity and stature in adolescence and earnings in young adulthood: analysis of a British birth cohort [see comments]. Arch Pediatr Adolesc Med 1994; 148( 7):681–7.
84. Garn SM, Clark DC. Nutrition, growth, development, and maturation: findings from the ten-state nutrition survey of 1968-1970. Pediatrics 1975; 56( 2):306–19.
85. Phillips RG, Hill AJ. Fat, plain, but not friendless: self-esteem and peer acceptance of obese pre-adolescent girls. Int J Obes Relat Metab Disord 1998; 22( 4):287–93.
86. Vanhala M, Vanhala P, Kumpusalo E, et al. Relation between obesity from childhood to adulthood and the metabolic syndrome: population based study. BMJ 1998; 317( 7154):319.
87. Decsi T, Molnar D, Koletzko B. Lipid corrected plasma alpha-tocopherol values are inversely related to fasting insulinaemia in obese children. Int J Obes Relat Metab Disord 1996; 20( 10):970–2.
88. Decsi T, Molnar D, Koletzko B. Reduced plasma concentrations of alpha-tocopherol and beta-carotene in obese boys. J Pediatr 1997; 130( 4):653–5.
89. Pinhas HO, Dolan LM, Daniels SR, et al. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents [see comments]. J Pediatr 1996; 128(5 Pt 1):608–15.
90. Decsi T, Molnar D, Koletzko B. Long-chain polyunsaturated fatty acids in plasma lipids of obese children. Lipids 1996; 31( 3):305–11.
91. Decsi T, Molnar D, Koletzko B. The effect of under- and overnutrition on essential fatty acid metabolism in childhood. Eur J Clin Nutr 1998; 52( 8):541–8.
92. Asayama K, Hayashi K, Hayashibe H, et al. Relationships between an index of body fat distribution (based on waist and hip circumferences) and stature, and biochemical complications in obese children. Int J Obes Relat Metab Disord 1998; 22( 12):1209–16.
93. Lurbe E, Alvarez V, Liao Y, et al. The impact of obesity and body fat distribution on ambulatory blood pressure in children and adolescents. Am J Hypertens 1998; 11(4 Pt 1):418–24.
94. Kratzsch J, Dehmel B, Pulzer F, et al. Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances. Int J Obes Relat Metab Disord 1997; 21:1130–6.
95. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000; 30:48–53.
96. Kinugasa A, Tsunamoto K, Furukawa N, et al. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gastroenterol. Nutr 1984; 3( 3):408–14.
97. Serdula MK, Ivery D, Coates RJ, et al. Do obese children become obese adults? A review of the literature. Prev Med 1993; 22( 2):167–77.
98. Power C, Lake JK, Cole TJ. Body mass index and height from childhood to adulthood in the 1958 British born cohort. Am J Clin Nutr 1997; 66( 5):1094–101.
99. He Q, Karlberg J. Prediction of adult overweight during the pediatric years. Pediatr Res 1999; 46( 6):697–703.
100. Blair SN, Brodney S. Effects of physical inactivity and obesity on morbidity and mortality: current evidence and research issues. Med Sci Sports Exerc 1999; 31(11 Suppl):S646–62.
101. Jung RT. Obesity as a disease. Br Med Bull 1997; 53( 2):307–21.
102. Must A, Jacques PF, Dallal GE, et al. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935 [see comments]. N Engl J Med 1992; 327( 19):1350–5.
103. Gunnell DJ, Frankel SJ, Nanchahal K, et al. Childhood obesity and adult cardiovascular mortality: a 57-y follow-up study based on the Boyd Orr cohort. Am J Clin Nutr 1998; 67( 6):1111–8.
104. Seidell JC, Visscher TL, Hoogeveen RT. Overweight and obesity in the mortality rate data: current evidence and research issues. Med Sci Sports Exerc 1999; 31(11 Suppl):S597–601.
105. Banerji MA, Faridi N, Atluri R, et al. Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. J Clin Endocrinol Metab 1999; 84:137–44.
106. Hughes K, Aw TC, Kuperan P, et al. Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore [see comments]. J Epidemiol Commun Health 1997; 51( 4):394–9.
107. 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( 12):2422–9.
108. Epstein LH, Myers MD, Raynor HA, et al. Treatment of pediatric obesity. Pediatrics 1998; 101:554–70.
109. Jeffery RW, Drewnowski A, Epstein LH, et al. Long-term maintenance of weight loss: current status. Health Psychol 2000; 19(1 Suppl):5–16.
110. Amador M, Ramos LT, Morono M, et al. Growth rate reduction during energy restriction in obese adolescents. Exp Clin Endocrinol 1990; 96( 1):73–82.
111. Figueroa CR, von AT, Franklin FA, et al. Comparison of two hypocaloric diets in obese children. Am J DisChild 1993; 147( 2):160–6.
112. Toubro S, Astrup A. Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake. BMJ 1997; 314( 7073):29–34.
113. Patton GC, Johnson SE, Wood K, et al. Abnormal eating attitudes in London schoolgirls–a prospective epidemiological study: outcome at twelve month follow-up. Psychol Med 1990; 20( 2):383–94.
114. Thompson JK, Coovert MD, Richards KJ, et al. Development of body image, eating disturbance, and general psychological functioning in female adolescents: covariance structure modeling and longitudinal investigations Int J Eat Disord 1995; 18( 3):221–36.
115. Becque MD, Katch VL, Rocchini AP, et al. Coronary risk incidence of obese adolescents: reduction by exercise plus diet intervention. Pediatrics 1988; 81( 5):605–12.
116. Rocchini AP, Katch V, Anderson J, et al. Blood pressure in obese adolescents: effect of weight loss. Pediatrics 1988; 82( 1):16–23.
117. Brownell KD, Wadden TA. Etiology and treatment of obesity: understanding a serious, prevalent, and refractory disorder. J Consult Clin Psychol 1992; 60( 4):505–17.
118. Epstein LH, Paluch RA, Gordy CC, et al. Decreasing sedentary behaviors in treating pediatric obesity Arch Pediatr Adolesc Med 2000; 154( 3):220–6.
119. Robinson TN. Reducing children's television viewing to prevent obesity: a randomized controlled trial. JAMA 1999; 282( 16):1561–7.
120. Holub M, Zwiauer K, Winkler C, et al. Relation of plasma leptin to lipoproteins in overweight children undergoing weight reduction. Int J Obes Relat Metab Disord 1999; 23( 1):60–6.