A Clinical Guide to Pediatric Weight Management and Obesity, 1st Edition

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Introduction: Medical Management of Obesity

Obesity

In ancient societies, obesity was traditionally seen as a sign of health and prosperity, because only prosperous individuals were assured of the ability to secure a stable, even abundant, supply of food in times of scarce resources. In addition, the ability to survive shifts in energy balance as a result of a variable food supply may have played a role in the selective survival of energy-efficient individuals. There has always been a crucial link between obesity and the individual's environment.

As the health of the population shifted, so did energy balance. In developing countries, improved nutrition, control of infectious diseases, and access to better living conditions have led to the ability to maintain increased energy stores as fat. In modern times, the rise of obesity in developing countries reflects this change in environmental conditions.

In the 1960s, for example, Chile experienced high maternal and infant mortality rates, along with a significant prevalence of infectious disease and malnutrition. In the succeeding 30 years, social programs were provided that increased the supply of food, improved educational systems and water and sanitation infrastructure, increased primary health care interventions, and lowered the unemployment rates. This meant that by the 1990s infant mortality had declined, mortality from communicable disease had decreased, and undernutrition was being replaced by obesity (1).

This pattern has been repeated in developing countries to such an extent that it, combined with the increase of obesity in more developed nations, has caused the World Health Organization to declare obesity a “worldwide epidemic” (2).

In developed countries, the trends driving the increase in obesity have not necessarily been the result of “positive” social and economic advancement. In the United

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States, for instance, Native Americans have experienced one of the fastest increases in obesity rates (3). In particular, the Pima Indian tribe has been among the most studied examples of the rapid rise of obesity secondary to shifts in the environment (4). The concept of the “thrifty genotype” has been advanced to explain the tendency of a population that has traditionally been exposed to cycles of food scarcity to become obese in the face of a stable and abundant food source (5). In the past one to two generations, as diets shifted toward increased fat intake and lifestyles became more sedentary, the rates of obesity rose alarmingly in the Pima population. By way of explanation, the composition of the Pima Indian diets of 100 years ago consisted of approximately 70% to 80% carbohydrate, 8% to 12% fat, and 12% to 18% protein; the current Pima diet consists of approximately 47% carbohydrate, 35% fat, 15% protein, and 3% alcohol (6). Factors affecting food choices on Indian reservations have been cost, availability, and shelf life. Higher fat foods available on reservations are cheaper, and lack of refrigeration makes purchase of perishable items such as fruits and vegetables less likely (7). At the same time dietary patterns were changing, physical activity was decreasing, with Pima children spending more time watching television and being less involved in sports than white children (8).

In more affluent environments where choices are possible, people make choices dictated by the “built environment” (9). The sociocultural desire to save time and decrease exertion may be driving the changes in the physical environment (9). “With our intelligence, we've acquired the knowledge to change our environment at speeds that our natural, evolutionary abilities cannot adapt to” (E. Zerhouni) (9). In light of the fact that “genetically, we are designed to eat when we can, and rest when we don't have to be physically active” (J. Hill) (9), these sociocultural environmental changes are not congruent with our genetic programming.

Childhood Growth

Poor growth has always been associated with poor health. In a pediatric medicine text from 1853, physicians were instructed to observe the child's size as an indicator of health or disease.

A child who has been healthy from its birth ought to have attained a certain average size and development at a certain age. If, on the contrary, it be much below the average size, if at three months it look like a newborn children, or at a year old like one of six months, it is very clear that something has acted to determine such slow and insufficient growth and it becomes the business of the practitioner to discover what the impeding cause has been (10).

Using growth charts to track the rate of weight and height gain has, until relatively recently, been focused on the child who is underweight or has slowing growth or “failure to thrive.” This type of growth pattern has been the impetus to closely examine the physical, psychosocial, and environmental influences that affect the child. Parents and families also have viewed the child's size and growth as an indicator of health, and in many cultures, parents prefer larger children. In 1999, a study of urban and rural Chinese families revealed that an increase in weight in young children was perceived as a sign of health and prosperity (11).

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The Balance Shifts

The rising rates of obesity in all countries have been explained by a shift in energy balance caused by an increasingly sedentary lifestyle, greater consumption of non-nutritious high-calorie “junk food,” increased eating frequency and portion size, and the emergence of television and computer use. The change in these environmental factors has not been hard to track and correlate with rising obesity rates in children. Actual causal links have been harder to establish. It is valuable to study attempts to analyze the trends that gave rise to shifts in population from underweight to overweight in an effort to understand the environmental forces acting on the population, which may have the potential to be changed.

In Chile, determinants of obesity were analyzed using data from a two-decade period between 1980 and 2000, when obesity increased at a rapid rate, with prevalence almost tripling. Environmental indicators, which relate to energy balance, were analyzed. Over this period, the mean caloric intake per day per person increased by 200 kcal, but this more than tripled when expressed as kilocalories per day per person living in poverty (1).

Two points may be made here. The first is that the daily increase of each 100 kcal beyond what is required to balance energy expenditure may be responsible for an approximate 10 lb per year weight gain in a person genetically susceptible to obesity; so, small amounts of caloric imbalance that occur consistently can account for substantial increases in weight. The second point is that food supplementation programs targeted to impoverished populations may have resulted in greater caloric imbalances at the same time that the energy expenditures were decreasing, resulting in a disproportionate weight gain. This is illustrated by data from the same study (1), which indicate that the numbers of cars, phones, and televisions in the population increased along with trends in the rise of sedentary behavior.

The Intrauterine Environment

Additional aspects of the interaction between the environment and the individual indicate that there may be susceptible periods in growth that sensitize the individual to obesity-promoting environments.

Young men whose mothers were exposed to undernutrition in the first and second trimesters of pregnancy during the Dutch famine of World War II were more likely to be obese than those whose mothers were exposed during the third trimester and those adults whose mothers were not undernourished (12).

Intrauterine growth may affect later body composition and deposition of adipose tissue. British men born with evidence of intrauterine growth retardation had greater waist-to-hip ratios for body mass index (BMI) than men of normal birth weight, indicating increased visceral fat deposition. Mexican and white Americans in the

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lowest third of birth weight had greater truncal fat than the highest third, which raises the possibility of an effect of intrauterine growth on body composition (13).

Diabetes in women during pregnancy has also been associated, in many studies, with an increased risk of diabetes and obesity in their children independent of maternal weight or infant birth weight (14). One hypothesis offered to explain this finding is that chronic hyperinsulinemia as a result of a hyperglycemic intrauterine environment might downregulate insulin receptors or post–insulin receptor signaling, giving rise to increasing insulin resistance in the child (15). Data from the National Health and Nutrition Examination Survey (NHANES) II for a sample of U.S. children between 2 and 47 months showed that babies born small for gestational age (SGA, birth weight <10th percentile) had a persistent deficit in lean body mass. At any given weight in this group, percent body fat was relatively higher for children who were SGA at birth (16).

In 1992, Hales and Barker (17) raised the possibility of the intrauterine environment's importance in “programming” a response to the nutritional environment later in life. Relative undernutrition in the intrauterine environment that causes a smaller than expected birth weight is associated with the development of obesity, diabetes, and cardiovascular disease in midlife. The mechanism for this increased risk is not known, but it raises the issue of the existence of vulnerable periods in growth and development that have a long-lasting effect on the response of the individual to the environment.

Infancy may be another vulnerable time in which rapid growth may predispose to later obesity. In a study of infant and childhood growth in an African American population, children who were in the highest growth percentiles at 4 months of age had a greater chance of being overweight by age 8 (18).

Gene-Environment Interaction

The “thrifty genotype” proposes that the genetics most suitable for survival in an energy-scarce environment of recurrent food shortages will cause weight gain in an energy-rich environment (5). Pérusse and Bouchard (19) have noted that “genotype-environment interactions arise when the response of a phenotype (e.g., fat mass) to environmental changes (e.g., dietary intervention) is modulated by the genotype of the individual.” They further speculate that these effects may explain individual responses to dietary constituents and/or susceptibility to obesity-related comorbidity (19).

A study of the effect of overfeeding on twin pairs showed that the difference in fat storage between pairs was sixfold greater than within pairs, indicating that genetic characteristics are modulating in response to energy surplus. In an exercise study, twins were more alike in their response to negative energy balance than were individuals of different genotypes (19). In the same way, carriers of a specific polymorphism in the lipoprotein lipase gene were shown to gain more weight and body fat in response to overfeeding than noncarriers (20).

Individual susceptibility to energy imbalance increases in importance as the environment becomes more obesity promoting, the interaction between the environment and the individual determining who will become obese in a given environment.

 

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Control of energy regulation has been proposed to reside within three distinct physiologic systems in the body: (a) the control of partitioning between protein and fat; (b) the nonspecific control of thermogenesis with afferent signals arising from food deprivation, nutrient deficiency, excess energy intake, and exposure to infection or cold stress; and (c) the adipose-specific control of thermogenesis, which is regulated by signals arising from the state of depletion of the adipose tissue fat stores (21).

The control of body energy partitioning operates during cycles of energy restriction (starvation) and energy abundance (refeeding). An individual's body composition dictates the proportion of protein and fat to be mobilized and used as fuel when starvation occurs and the proportion of deposition of protein and fat during refeeding (21). This explains why weight gain in obesity is due to an increase in both adipose tissue and lean body mass, the proportions of which vary in each individual (22). With the same excess caloric intake, then, an individual with a low partitioning characteristic will gain more fat and less protein than an individual with a high partitioning characteristic (21). This characteristic may be one of the major genetically determined physiologic variables in the development of obesity (21).

Nonspecific control of thermogenesis or diet-induced thermogenesis is regulated by the sympathetic nervous system and can be affected by energy supply, diet composition, nutrient deficiencies, ambient temperature, and psychological stress (21). This control system suppresses thermogenesis under conditions of energy scarcity, and the suppression is rapidly removed when food becomes available again. The system may have evolved as a mechanism for regulating the supply of essential nutrients rather than overall energy balance (23). For example, excess calories consumed from a poor diet in an effort to replace essential nutrients would trigger diet-induced thermogenesis to avoid excess weight gain. Individual differences in diet-induced thermogenesis are greater when high- or low-protein diets are overfed. Stock (23) maintains that this could provide a highly sensitive method for discriminating between those who are, in metabolic terms, resistant to obesity and those who are susceptible to it.

Adipose-specific thermogenesis is a process that causes a disproportionate deposition of fat relative to lean tissue in a cycle of weight recovery after energy scarcity (21). This mechanism is believed to have survival value because fat has a greater energy density and lower cost of maintenance than lean tissue and would enable an individual to rapidly build back an energy reserve for the next food shortage (21).

Health and Disease in Childhood: A Shifting Paradigm

In the early part of the 20th century, efforts to improve child health focused on vaccination, treatment of infectious disease and cancer, and improvement in nutrition. Obesity-related comorbidities were not in evidence. No physician in training 25 years ago expected to see a 12-year-old with type 2 diabetes or a teen with nonalcoholic hepatosteatosis. Obesity was just beginning to increase, and the obesity-related diseases hovered on the horizon. The obesity-related comorbidities that are discussed in this book represent “new morbidity” for children, which will require prevention efforts, intervention, and treatment strategies. Increased understanding of the

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pathophysiology, evolution, and treatment of these diseases can help physicians stem the rising tide of morbidity that threatens the health of children and adolescents.

References

  1. Kain J, Burrows R, Uauy R. Obesity trends in Chilean children and adolescents; basic determinants. In: Chen C, Dietz W, eds. Obesity in childhood and adolescence, Nutrition Workshop Series. Pediatric Program, Vol. 49. Nestec Ltd. Philadelphia: Vevey/Lippincott Williams & Wilkins; 2002:45–64.
  2. World Health Organization. Global Strategy on Diet, Physical Activity and Health. http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/
  3. Story M, Evans M, Fabsitz RR, Clay TE, Holy Rock B, Broussard B. The epidemic of obesity in American Indian communities and the need for childhood obesity prevention programs. Am J Clin Nutr.1999;69(4):747S–754S.
  4. Tataranni PA, Harper IT, Snitker S, Del Parigi A, Vozarova B, Bunt J, Bogardus C, Ravussin E. Body weight gain in free-living Pima Indians: effect of energy intake vs. expenditure. Int J Obes Relat Metab Disord.2003;27(12):1578–1584.
  5. Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by progress. Am J Hum Genet.1962;14:353–362.
  6. Boyce VL, Swinburn BA. The traditional Pima diet: composition and adaptation for use in a dietary intervention study. Diabetes Care.1993;16(1):369–371.
  7. Ballew C, White L, Strauss K, Benson L, Mendlein J, Mokdad A. Intake of nutrients and food sources of nutrients among the Navajo: findings from the Navajo Health and Nutrition Survey. J Nutr.1997;127(10 suppl):2085S–2093S.
  8. Fontvieille A, Kriska A, Ravussin E. Decreased physical activity in Pima Indians compared with Caucasian children. Int J Obes Relat Metab Disord.1993;17(8):445–452.
  9. Spotswood S. NIH highlights link between obesity and environment. US Medicine, July 2004. Available at: http://www.usmedicine.com/article.cfm?articleID=902&issueID=64 (accessed July 14, 2006).
  10. Forsyth Meigs J. Practical treatise on the diseases of children, 3rd ed., carefully revised. Philadelphia: Lindsay and Blankiston; 1858.
  11. Ma G. Environmental factors leading to pediatric obesity in the developing world. In: Chen C, Dietz W, eds. Obesity in childhood and adolescence.Nestle Nutrition Workshop Series. Pediatric Program, Vol. 49. Nestec Ltd. Philadelphia: Vevey/Lippincott Williams & Wilkins; 2002:195–206.
  12. 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):349–353.
  13. Jackson AA, Langley-Evans SC, McCarthy HD. Nutritional influences in early life upon obesity and body proportions. Ciba Found Symp.1996;201:118–137, 188–193.
  14. Whitaker RC, Dietz WH. Role of prenatal environment in the development of obesity. J Pediatr.1998;132(5):768–776.
  15. Singhal A, Lanigan J, Lucas A. Early origins of obesity. In: Chen C, Dietz W, eds. Obesity in childhood and adolescence.Nestle Nutrition Workshop Series. Pediatric Program. Vol. 49. Nestec Ltd. Philadelphia: Vevey/Lippincott Williams & Wilkins; 2002:83–97.
  16. Hediger ML, Overpeck MD, Kuczmarski RJ, McGlynn A, Maurer KR, Davis WW. Muscularity and fatness of infants and young children born small or large for gestational age. Pediatrics.1998; 102(5):E60.
  17. Hales CN, Barker DJ. Type 2 (non-insulin dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia.1992;35(7):595–601.
  18. Stettler N, Kumanyika SK, Katz SH, Zemel BS, Stallings VA. Rapid weight gain during infancy and obesity in young adulthood in a cohort of African Americans. Am J Clin Nutr.2003;77(6): 1374–1378.
  19. Pérusse L, Bouchard C. Gene-diet interaction in obesity. Am Clin Nutr.2000;72(5 suppl): 1285S–1290S.
  20. Bouchard C, Dionne FT, Chagnon M, Moreel JF, Pérusse L. DNA sequence variation in the lipoprotein lipase (LPL) gene and obesity.FASEB J.1994;8:923(abst).
  21. Dulloo AG, Jacquet J. Toward understanding the genetic basis of human susceptibility to obesity: a systemic approach. In: Chen C, Dietz W, eds. Obesity in childhood and adolescence.Nestle Nutrition Workshop Series. Pediatric Program, Vol. 49. Nestec Ltd. Philadelphia: Vevey/Lippincott Williams & Wilkins; 2002:143–161.
  22. Forbes GB. Lean body mass-body fat interrelationship in humans. Nutr Rev.1987;45(8):225–231.
  23. Stock MJ. Gluttony and thermogenesis revisited. Int J Obes Relat Metab Disord.1999;23:1105–1117.