Para compra cialis puede ser visto como un desafío. Aumenta Smomenta, y todos los que se poco a poco abrumado, como es lógico, cada vez más hombres están diagnosticados con disfunción eréctil.

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The Journal of Clinical Endocrinology & Metabolism 90(3):1871–1887 Copyright 2005 by The Endocrine Society CONSENSUS STATEMENT: Childhood Obesity
Phyllis W. Speiser, Mary C. J. Rudolf, Henry Anhalt, Cecilia Camacho-Hubner, Francesco Chiarelli,Alon Eliakim, Michael Freemark, Annette Gruters, Eli Hershkovitz, Lorenzo Iughetti, Heiko Krude,Yael Latzer, Robert H. Lustig, Ora Hirsch Pescovitz, Orit Pinhas-Hamiel, Alan D. Rogol,Shlomit Shalitin, Charles Sultan, Daniel Stein, Pnina Vardi, George A. Werther, Zvi Zadik,Nehama Zuckerman-Levin, and Zeev Hochberg, on behalf of the Obesity Consensus Working Group Schneider Children’s Hospital (P.W.S.), New Hyde Park, New York 11040, and New York University School of Medicine, NewYork, New York 10016; East Leeds Primary Care Trust (M.C.J.R.), University of Leeds, Leeds LS2 9DE, United Kingdom; St.
Barnabas Medical Center (H.A.), Livingston, New Jersey 07039, and State University of New York Downstate Medical School,Brooklyn, New York 11203; William Harvey Research Institute (C.C.-H.), University of London, London EC1A 7BE, UnitedKingdom; University of Chieti (F.C.), Chieti, Italy 66100; Meir General Hospital (A.E.) and Felsenstein Medical Research Center(P.V.), Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel 69978; Schneider Children’s Medical Center, Petah-Tikva49202, and Sackler Faculty of Medicine (S.S.) and Chaim Sheba Medical Center and Sackler Faculty of Medicine (D.S.), Tel AvivUniversity, Tel Aviv, Israel 69978; Duke University Medical Center (M.F.), Durham, North Carolina 27710; University Children’sHospital (A.G., H.K.), Charite, Humboldt-University, Berlin, Germany 10099; Soroka University Medical Center (E.H.), Beer-Sheva, Israel 84101; University of Modena and Reggio Emilia A (L.I.), Modena, Italy 41100; Meyer Children’s Hospital (Y.L.,N.Z.-L., Z.H.), Rambam Medical Center, Haifa, Israel 31096; University of California San Francisco (R.H.L.), San Francisco,California 94143; James Whitcomb Riley Hospital for Children (O.H.P.), Indiana University School of Medicine, Indianapolis,Indiana 46202; Safra Children’s Hospital (O.P.-H.), Sheba Medical Center, Tel Hashomer, Israel 52662; University of Virginia(A.D.R.), Charlottesville, Virginia 22911; Hopital Arnaud de Villeneuve (C.S.), Montpelier, France F-34295; Murdoch ChildrensResearch Institute (G.A.W.), University of Melbourne, Royal Children’s Hospital, Parkville, Victoria, Australia 3052; and KaplanMedical Center (Z.Z.), Rehovot, Israel 76100
In March 2004 a group of 65 physicians and other health pro-
electronic communication each group selected the key issues
fessionals representing nine countries on four continents con-
for their area, searched the literature, and developed a draft
vened in Israel to discuss the widespread public health crisis
document. Over the 3-d meeting, these papers were debated
in childhood obesity. Their aim was to explore the available
and finalized by each group before presenting to the full group
evidence and develop a consensus on the way forward.
for further discussion and agreement.
The process was rigorous, although time and resources did
In developing a consensus statement, this international
not permit the development of formal evidence-based guide-
group has presented the evidence, developed recommenda-
lines. In the months before meeting, participants were allo-
tions, and provided a platform aimed toward future corrective
cated to seven groups covering prevalence, causes, risks, pre-
action and ongoing debate in the international community.
vention, diagnosis, treatment, and psychology. Through
(J Clin Endocrinol Metab 90: 1871–1887, 2005)
Prevalence
ples, the prevalence of overweight doubled among chil- dren 6 –11 yr of age and tripled among those 12–17 yr ofage in the United States between the second National There has been a worldwide increase in obesity among Health and Nutrition Examination Survey, conducted be- people of all ages. The definition of obesity varies but is tween 1976 and 1980, and the most recent such survey, based on body mass index (BMI) cutoffs described below.
conducted in 1999 and 2000. Approximately 14 –15% of all As many as 250 million people, or about 7% of the current 15 yr olds in the United States can be classified as obese world population, are obese. Two to three times more (1). African-Americans, Hispanics (predominantly Mexi- people are overweight. In one of the most extreme exam- can and Puerto Rican), Pima Indians, and other NativeAmericans have a particularly high predisposition to obe- First Published Online December 14, 2004
sity. There are national differences in prevalence rates for Abbreviations: AHI, Apnea-hypopnea index; BBS, Bardet-Biedl syn- obesity (2). Comparison of cross-sectional data from drome; BIA, bioelectric impedance assay; BMI, body mass index; BWS, school-based surveys conducted in 1997 and 1998 describ- Beckwith-Wiedemann syndrome; DEXA, dual-energy x-ray absorpti- ing body size among adolescents in 13 European countries, ometry; GDM, gestational diabetes mellitus; HDL, high-density lipopro-tein; IOTF, International Obesity Task Force; LDL, low-density lipopro- Israel, and the United States showed that the United States, tein; MCR, melanocortin receptor; MS, metabolic syndrome; OGTT, oral Ireland, Greece, and Portugal had the highest prevalence glucose tolerance test; OSA, obstructive sleep apnea; POMC, proopio- of overweight (Table 1) (3). A review of 21 surveys con- melanocortin; PWS, Prader-Willi syndrome; RYGB, Roux-en-Y gastric ducted in various European countries indicated a higher bypass; SES, socioeconomic status; T2DM, type 2 diabetes mellitus.
prevalence of overweight in western and southern Europe.
JCEM is published monthly by The Endocrine Society (http://www.
The countries surrounding the Mediterranean showed endo-society.org), the foremost professional society serving the en-
docrine community.

prevalence rates for overweight children in the range of J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity TABLE 1. Prevalence of BMI Ն85th and Ն95th percentiles of
accurate, and reproducible method to measure fat mass in infants, children, or adolescents and the lack of cutoffs of fatmass for children to identify individuals at moderate or high cardiovascular and metabolic risk in childhood and adult- hood. Whitaker et al. (12) demonstrated that the prognostic importance of obesity in infancy and childhood depends on the presence or absence of obesity in one or both parents.
It is important to distinguish between primary or idiopathic obesity and the rarer situation of secondary obesity owing to genetic disorders, endocrine disease, central nervous system lesions, or iatrogenic causes. Detailed medical history, physical examination, and laboratory tests are helpful.
In the initial assessment of the overweight or obese child, nutritional history should include breast-feeding or formula; age at introducing solids; and assessment of caloric intake, including dietary quality in terms of the balance of nutrients and food groups. The clinician should ask about the child’slevel of physical activity; limitations due to weight; and respiratory difficulties including snoring and somnolence,potential signs of sleep apnea.
20 – 40%, whereas those in northern areas showed lower Physical examination should first be directed to overall rates, in the range of 10 –20% (4).
body proportions and the presence or absence of any dis- Evaluation of Australian children from surveys taken 10 yr tinctive or dysmorphic features that could guide the diag- apart also showed an increase of overweight and obesity. By nosis to rare obesity syndromes. Recording and graphical 1995 15% of boys and 15.8% of girls were overweight, and plotting of height, weight, BMI, and waist circumference 4.5% of boys and 5.3% of girls were classified as obese (5). In other Asian populations, Polynesians, Micronesians, An-urans, and Maoris are at high risk for obesity.
Quantitation of body fat in childhood and adolescence. Over- There has also been a trend toward increasing prevalence weight and obesity occur with excessive accumulation of of overweight and obesity as well as metabolic complications body fat. Because increasing body fat is associated with in- in developing countries. Regions with the highest prevalence creasing morbidity, the definition of overweight and obesity of overweight were: the Middle East, 7%; North Africa, 8%; should be linked to health risks. Due to difficulties in direct and Latin America and the Caribbean, 4.5–7% (6).
measurement of body fat, obesity can be simply and inex- Overweight children often become overweight adoles- pensively estimated using the BMI. BMI correlates with the cents and adults (7), and overweight in adulthood is a serious amount of body fat in both children and adults (13). The health risk (8). Obesity is associated with the development of World Health Organization (WHO) classification and U.S.
a number of serious medical complications and increased dietary guidelines for obesity in adults define overweight mortality in children and adults. Thus, monitoring trends in based on health risk as a BMI of 25–30 kg/m2 and obesity as the prevalence of obesity in populations worldwide is im- portant for epidemiological assessment.
Country-specific growth charts have been developed based on cross-sectional and longitudinal data. For example, the U.S.
Centers for Disease Control and Prevention (CDC) 2000 growth Man has evolved under conditions of stress in which it was charts include gender-specific BMI for age growth charts for advantageous to be able to store fat (9). It is this genetic ages 2–19 yr (14). These charts were developed from five na- propensity to store fat in response to insulin, paired with our tional data sets in the United States. Overweight and obesity lifestyles with too much sedentary activity and processed among individuals 2–19 yr old are defined as the 95th percentile energy-dense foods, that has contributed to the problem of or greater of BMI for age; those with BMI between the 85th and overweight. Numerous genetic markers have been linked 95th percentiles are considered at risk for overweight. In a with obesity and its metabolic consequences (10), yet iden- separate report from the National Heart, Lung, and Blood In- tifiable hormonal, syndromic, or molecular genetic abnor- stitute, overweight is defined in adolescents as the 85th per- malities can presently account for less than 5% of obese centile or greater of BMI for age (15). A recent review concluded individuals (11). This is discussed in greater detail in Causes.
that the evidence for use of national BMI reference data issufficiently strong for its adoption in clinical practice and Diagnosis
screening (16). An advantage of these charts is that a child canbe followed up over time with graphical plotting of serial BMI Clinical evaluation: How do we evaluate overweight and measures. A disadvantage is that the charts are based on ar- bitrary statistical measures and not on biological data related to Basic evaluation: history and anthropometrics. The definition the risk of later morbidity. Moreover, the CDC reference data of overweight and obesity in childhood is still a matter of are based on American children and may not be applicable to debate for two main reasons: the lack of a simple, low-cost, other populations. Another problem with this approach is that Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 as the population becomes heavier, these percentiles define that has high precision and simplicity for the subject. X-ray changing thresholds for overweight and obesity.
exposure is minimal. DEXA also is limited by the inability to To have an absolute and internationally relevant definition distinguish between sc and visceral fat. The method is most of child overweight and obesity, Cole et al. (2) developed age- and sex-specific cutoff lines from data derived from six coun-tries across several continents using BMI. These charts ex- Imaging. Computed tomography and magnetic resonance trapolate risk from the adult experience to children. The imaging of the abdomen are accurate methods that can be International Obesity Task Force (IOTF) has recommended used to measure visceral fat (20). However, the disadvan- this approach for the comparison of populations (17). IOTF tages are high cost and radiation exposure with computed currently defines overweight as approximately 91% or tomography. These methods require more time to perform greater and obesity as approximately 99% or greater. The and specialists for interpretation. Therefore, these methods charts of Cole et al. are recommended for epidemiologic are also recommended only for research purposes.
purposes and may underestimate the prevalence of obesity Anthropometrics. Waist circumference or waist to hip ratios if applied to cross-sectional charts. Owing to the lack of are used as indirect markers of intraabdominal adipose tis- precise percentiles, these charts are not useful for longitu- sue. As with BMI, there is some controversy as to appropriate dinal follow-up of individual patients.
cutoffs for adults. Waist circumferences above 95 cm indicate Quantitation of body fat in infancy. Weight for length is elevated mortality rates (21). This parameter is also a pre- usually used in the under 2-yr age group. In the United dictor of cardiovascular and metabolic risk factors in obese States, overweight in this age group is defined as greater than children (22). Visceral or intraabdominal adiposity is also the 95th percentile of the weight for length. The definition is associated with the metabolic syndrome (see definitions inRisks purely statistical, and the percentile values are age and gen- ) in adults and children. Methodologies such as DEXA, der specific. It is important to measure head circumference skinfolds, and BIA do not assess visceral fat. Thus, waist because a very large head may alter weight-for-length ratio.
circumference should be included in clinical practice as theleast invasive and least costly tool to help identify obesechildren at higher metabolic risk. Currently there are limited pediatric reference values for waist circumference (24, 25), What are the most reliable methods of assessment of body fat and its distribution? As discussed, BMI, an indirect estimate oftotal adiposity, does not necessarily predict health risk for children. There are some situations in which BMI gives an Genetic: which genes are important determinants of obesity? inaccurate picture, e.g. in short muscular people. Further-more, BMI does not distinguish between sc and visceral fat.
Monogenic obesity. Leptin was the first specific gene recog- It is therefore useful to employ adjunctive measures of total nized as important in human body weight control. This adi- pocyte hormone is involved in a complex circuit of hormonesand neurotransmitters to control appetite (Table 2). To date, Skinfold thickness. This is a quick, simple, inexpensive several monogenic obesity syndromes have been identified, method, which is useful for community pediatrics and large and most involve the leptin-melanocortin regulation path- studies and gives information on fat distribution because it way (26, 27). The known genes include leptin, the leptin is done at several body sites. It does not require a high degree receptor proopiomelanocortin (POMC), prohormone con- of technical skill, although the technique requires a trained vertase 1, melanocortin receptors 3 and 4, and the transcrip- person to standardize the measurements; otherwise it is tion factor single-minded 1; the list will continue to expand.
poorly reproducible, especially at the highest BMIs. Triceps Severe and early-onset obesity, common findings in mono- skinfold is correlated with fat mass and, combined with BMI, genic cases, parallels the phenotype in the corresponding increases the sensitivity for the determination of percent knockout mice and supports the central role of these genes in body weight regulation. There have been conflicting re-ports about the association between obesity and human poly- Bioelectric impedance assay (BIA). BIA is a method of body morphisms in genes involved in the regulation of peripheral composition assessment that is simple, quick, relatively in- metabolic control, e.g. mitochondrial uncoupling genes, per- expensive, and noninvasive. However, BIA measurements haps attributable to ethnic or gender-specific variations (28).
are highly variable because they are affected by meals; phys- Homozygous mutations of the leptin-melanocortin genes ical activity; and other variables that change the subject’s are extremely rare causes of severe obesity and are often hydration state, such as menstrual phase, acute illness, kid- associated with other features, e.g. hypogonadotropic hypo- ney disease, and water and electrolyte disturbances (19).
gonadism in leptin deficiency (26) and red hair and hypo- Hydrodensitometry. Underwater weighing requires special cortisolism in POMC deficiency (29) resulting in phenotypes equipment and is used primarily for research purposes; it is that exclude these genes as likely candidates for common not available for routine clinical care. It is useful for valida- obesity. In the case of leptin, leptin receptor, and POMC tion of other methods of measuring body fat.
genes, heterozygous mutation carriers have a minimally ab-normal phenotype. Heterozygous mutations causing signif- Dual-energy x-ray absorptiometry (DEXA). This is a rela- icant obesity are found only in the melanocortin receptor tively expensive but safe method for assessing total body fat (MCR) 4 and are not associated with an otherwise distinctive J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity TABLE 2. Factors critical in the regulation of appetite and energy balance
Central nervous system-appetite regulation command: Ventro-medial-hypothalamus, paraventricular nucleus, lateral hypothalamus area Cocaine and amphetamine reg. transcript (CART) Opioids (␤-endorphin, dynorphin, met-enkephalin) Parasympathetic nervous system: vagus nerve Energy storage by glucose-stimulated insulin secretion Sympathetic nervous system: ␣-adrenergic activation Stress, cold (lipolysis, heat production, thyroid activation) phenotype. To date, MC4R mutations are the most frequent the presence of elevated ghrelin levels contrasting with de- known cause of monogenic human obesity, occurring in up creased levels in other forms of obesity. Ghrelin, an orexi- to 4% of early-onset and severe childhood obesity (30).
genic protein, may be responsible, at least in part, for thehyperphagia observed in PWS (34).
Other candidate genes involved in human obesity. Because in- Bardet-Biedl syndrome (BBS; OMIM no. 209900) is char- sulin plays a crucial role in energy metabolism, the insulin acterized by a variable degree of obesity; mental retardation; gene has been examined. There is an association between and pigmentary retinopathy, polydactyly, and renal abnor- variable nucleotide tandem repeat polymorphisms upstream malities (35). Based on several large pedigrees with mainly of the insulin gene, increased fasting insulin levels, and child- recessive inheritance of the BBS phenotype, several chromo- hood obesity in individuals of European descent (31).
somal regions, including genes involved in cilial and cent- The human obesity gene map continues to expand as more riole function, have been identified (36).
genes and chromosomal regions are linked with human obe- Beckwith-Wiedemann syndrome (BWS; OMIM no. 130650) sity. In the most recent published update, there were more is principally characterized as a syndrome of generalized fetal than 430 genes, markers, and chromosomal regions associ- overgrowth and visceromegaly with tall stature but not ated or linked with human obesity phenotypes. There are 35 genomic regions with quantitative trait loci that have beenreplicated in two or more studies of obesity phenotypes (32).
Every chromosome, except the Y chromosome, has had loci Endocrine: are endocrine disorders a common cause of linked with the phenotype of obesity. Some genes have been identified that are specific to visceral obesity. Most of the Although rare among children and adolescents with obe- specific genes involved are as yet unknown. In view of these sity, GH deficiency, thyroid hormone deficiency, and cortisol data, it is highly probable that childhood obesity is polygenic excess are characterized by a combination of decreased en- with susceptibility conferred via complex genetic factors. It ergy expenditure and decreased growth resulting in prom- is estimated that 30 –50% of the tendency toward excess ad- inent central adiposity in a short, slowly growing child. GH iposity can be explained by genetic variations (33).
therapy in individuals with GH or IGF-I deficiency reverses Which syndromes are associated with early childhood obesity? these changes in body composition, reducing fat mass while Obesity is a component of several rare human genetic increasing muscle mass (37). Thyroid hormone replacement syndromes that present with characteristic phenotypes; two increases resting metabolic rate and improves impaired se- of these are described here. Prader-Willi syndrome (PWS; cretion of GH and IGF-I production that accompany thyroid OMIM no. 176270) is characterized by intrauterine hypoto- hormone deficiency. Patients with excessive cortisol levels nia, mental retardation, and hypogonadotropic hypogonad- often have hypertension, glucose intolerance, dyslipidemia, ism. The obesity of PWS that occurs in early childhood is moon facies, decreased muscle mass, and broad violaceous resistant to diet and associated with early mortality. PWS is striae in addition to visceral obesity and poor growth. Re- caused by the loss of paternally expressed genes, including moving the glucocorticoid source ameliorates these prob- small nuclear ribonucleoprotein, within the PWS critical re- lems (38). Insulin and leptin are produced in the periphery, gion on chromosome 15q; however, the precise metabolic circulate at levels proportional to body fat content, and enter functions of the missing gene products remain unknown.
the central nervous system in proportion to their plasma One major difference in the obesity associated with PWS is level. Receptors for leptin and insulin are expressed in brain Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 neurons involved in regulating energy intake; administra- newer antipsychotic drugs can cause a rapid increase in body tion of either peptide directly into the brain induces satiety weight. There is, however, considerable variability among (39). Hyperinsulinism, relative insulin resistance, and to a the various drugs in their effect on weight gain, lipid profile, lesser extent type 2 diabetes mellitus (T2DM) are recognized and risk of diabetes. The prevalence of both diabetes and comorbidities of obesity in the young (40). Insulinomas are hyperlipidemia among individuals with schizophrenia and rarely diagnosed in children. With hyperinsulinism and nor- affective disorders is 1.5–2 times higher than the general mal insulin sensitivity, symptoms of hypoglycemia would population (43). Among the second-generation drugs, which herald the diagnosis before the onset of obesity in most cases.
have generally replaced first generation, clozapine and olan- Most obese individuals have elevated circulating insulin and zapine, have a marked effect on weight gain, with increased leptin levels and are relatively resistant to the satiety-induc- risks for developing diabetes and hyperlipidemia. Risperi- done and quetiapine have a moderate effect on weight gain Pseudohypoparathyroidism is a rare cause of childhood and possible effects on development of diabetes and hyper- obesity, also associated with PTH resistance with hypocal- lipidemia. Aripiprazole and ziprasidone are associated with cemia and hyperphosphatemia, short stature, round face, less weight gain and better glucose: insulin and lipid profiles; short metacarpals, basal ganglia calcification, and develop- however, there is less long-term experience with the latter Laboratory investigations directed at identifying comor- bidities of obesity may include thyroid functions, lipid pro- Environment: how does environment contribute to the file, complete chemistries and hepatic profile, and fasting genetic predisposition to obesity? glucose and insulin. An oral glucose tolerance test (OGTT)should be considered to exclude impaired glucose tolerance Genes play a permissive role and interact with environ- or T2DM in individuals at high risk, e.g. family history of mental factors to promote obesity. Studies of energy balance T2DM and/or metabolic syndrome, after 10 yr of age. De- among pairs of monozygotic twins have shown that subjects termination of serum or urinary cortisol levels should be with the same genotype are more alike in response to energy reserved to exclude the presence of Cushing’s syndrome in surplus and deprivation than are subjects with different ge- obese individuals who have appropriate historical informa- notypes for changes in circulating lipid levels, sc fat, fat mass, and visceral fat in response to dietary changes. Advances in Infants who are hypoglycemic or require very frequent feed- the ability to generate genotypic information, in combination ings as well as infants with dysmorphic features require further with precise phenotypic markers, will improve our capacity evaluation. Examples include persistent hyperinsulinemic hy- to better determine gene-environment interactions (45).
poglycemia of infancy (OMIM no. 601820) and BWS with hy- Does the in utero milieu contribute to obesity? Epidemiological poglycemia, or PWS and BBS with dysmorphism.
studies of the impact of maternal gestational diabetes mel-litus (GDM) on adolescent obesity demonstrate conflicting Neurologic: how can central nervous system lesions results. Infants of Pima Indians with GDM had an increased risk of obesity, compared with siblings born before their Obesity is a frequent complication in children surviving mothers developed GDM. This study supports the role of in serious brain injury, brain tumors, and/or cranial irradiation.
utero exposure to hyperglycemia as a risk factor for subse- Significant increases in weight are noted to occur in the early quent obesity (36). Other studies (37, 38) demonstrated an postoperative period. These children often have reduced increased risk of adolescent overweight associated with in- physical activity more than increased energy intake. The creased birth weight and maternal GDM, yet the association pattern of decreased physical activity may be secondary to was attenuated or lost completely after adjustment for ma- suboptimal hormonal replacement and decreased sympa- ternal BMI. Thus, the effect of fetal hyperinsulinemia on body thetic nervous system function. The exact mechanisms re- composition and size at birth may set the stage for the future sponsible for this phenomenon are still unknown, although alterations in hypothalamic neuropeptides (41) and en-hanced activity of 11-␤ hydroxysteroid dehydrogenase, con- verting cortisone to cortisol (42), have been implicated. These What is the impact of socioeconomic status (SES), race, ethnicity, individuals often have autonomic dysregulation of the ␤-cell, and gender? Most of the data in this area are derived from the with insulin hypersecretion in response to oral glucose tol- adult population in the United States (46). In general, those with lower income and education levels are more likely tobecome obese than those with higher income levels and Medications: do medications cause obesity? higher education levels, who may have greater awareness of High-dose, chronic glucocorticoid treatment is well and access to health care, healthy foods, and fitness facilities.
known to be associated with a distinctive pattern of centrip- The prevalence of obesity is higher in racial and ethnic etal weight gain with visceral fat accumulation predisposing minorities, perhaps attributable to greater poverty among to cardiovascular risk. Other drugs used in children and these groups. Selective weight gain in certain populations adolescents that may predispose to weight gain include may also indicate that the interaction between people and cyproheptadine, valproate, and progestins.
their environment varies according to genetic background.
There is considerable evidence that treatment with some Clearly some populations are at greater risk of obesity- J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity related morbidity. Therefore, effective prevention and treat- What is the psychological profile of obese children and adolescents? ment may require racial and ethnic-specific strategies.
A causal relationship between obesity and psychological fac- Gender influences the impact of SES and ethnicity on the tors remains unclear. Adiposity is very visible, and children development of obesity in that a poor woman is twice as tend to rate disease and minor deformities as preferable to likely to become obese as a poor man. Conversely, a wealthy obesity at 6 yr of age. Children’s perceptions of obesity em- woman is less likely to become obese than a wealthy man.
phasize laziness, selfishness, lower intelligence, social isola- However, a wealthy man is significantly more likely to be tion, poor social functioning, and academic success as well overweight than a man with low SES. Overall, women are as low levels of perceived health, healthy eating, and activity more likely to be obese than men. In view of the influence of (62). Thus, children share the overall negative societal per- maternal BMI on their children, this is especially concerning.
ceptions toward those who are overweight or obese. This is According to the American Obesity Association, among regardless of the child’s own weight status or gender. Chil- women between the ages of 20 and 74 yr, 34% are obese dren as young as 5 yr are aware of their own fatness, which (BMI Ն 30) and 6.3% are severely obese (BMI Ն 40), com- impacts their perceptions of appearance, athletic ability, so- pared with 28 and 3.1%, respectively, for men (47).
cial competence, and self-worth. Quality of life is poor amongobese youngsters by parental and self-report (63). Self- What is the role of lifestyle and diet? Studies using motion esteem in obese children varies with gender and age. Females sensors have shown that children who spend less time in are at greater risk for self-esteem problems (64). Parental moderately vigorous activity are at higher risk to become acceptance or lack of concern may be a protective factor for obese during childhood and adolescence (48). In the United States, only about 25% of adolescents report regular exercise, Among severely obese adolescents, 48% have moderate to and an alarming 14% say they do not exercise at all. Tele- severe depressive symptoms and 35% report high levels of vision and video games have contributed to more sedentary anxiety. Obese girls are more likely to have attempted suicide leisure activities as well as increased snacking and inappro- than nonobese girls. Overweight adolescents reported en- priate food choices due to television advertising. There is a gaging in significantly more unhealthy behaviors and expe-riencing more psychosocial distress than their nonover- positive correlation between hours of television viewing and weight peers. Overweight adolescents were found to be more overweight, especially in older children and adolescents (49).
isolated and peripheral to social networks than were their Aside from these lifestyle issues, eating patterns of chil- dren and adolescents have changed dramatically in the pastfew decades (50). Dietary factors that place children at risk for obesity include high fat and excess calorie intake. Obesechildren tend to skip breakfast but consume a large amount Childhood obesity is now recognized as a major medical In terms of dietary content, there is an inverse relationship and public health problem. Obesity in adults is strongly between calcium intake and adiposity (52). The consumption associated with many serious medical complications that of high-carbohydrate soft drinks is a major contributing fac- impair quality of life and lead to increased morbidity. Obese tor to high calorie counts (53), especially because these fluids children are at high risk for adult obesity, but there are as yet tend to replace milk and calcium intake for adolescents.
insufficient data to assign specific risk levels in childhood.
Additionally, fast food consumption now accounts for 10% However, obesity in childhood provides an independent of food intake in children in U.S. schools, compared with 2% contribution to the development of adult morbidity. Without in the 1970s. Children who frequently eat fast food consume proper intervention, adult morbidities will likely begin to more total energy, more energy per gram of food, more total appear in the young. There are strong epidemiologic and fat, more total carbohydrate, more added sugars, less fiber, causal links between obesity in the young and earlier-onset less milk (calcium), and fewer fruits and vegetables than children who eat fast food infrequently (50, 54). Those whoare overweight are particularly vulnerable to the adverse health effects of consuming fast foods (55).
Over the past decade, there has been an alarming increase It appears that neonatal nutrition has an impact on child- in the appearance of T2DM in children, a disease that for- hood and adolescent obesity. In particular, breast-feeding merly occurred almost exclusively in adults. T2DM in youth has been shown to have at least some protective effect in represents the most rapidly growing form of diabetes in some populations (56, 57), although this has been refuted in America, Europe, Japan, and Australasia, now responsible for up to about one fifth of new diagnoses of diabetes inpubertal children. Although universal screening is not rec- Is binge eating a major cause of obesity? Twenty to 40% of ommended, the American Academy of Pediatrics and Amer- severely obese adults (59) and adolescents (60) suffer from ican Diabetes Association recommend that all youngsters binge eating. Obese binge eaters show weight and shape who are overweight and have at least two other risk factors concern as well as symptoms of depression and anxiety with should be tested for T2DM beginning at age 10 yr or at the lower self-esteem when compared with nonbingeing obese onset of puberty and every 2 yr thereafter (66). The risk individuals. Apparently binge eating disorder in youngsters factors include family history of T2DM in first- or second- does not develop into bulimia nervosa in later life (61).
degree relatives; belonging to certain ethnic groups (i.e. Na- Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 tive American, African-American, Hispanic, Japanese, or be derived from fat in young women (75). There is also a other Asian/Pacific Islander); or having signs associated causal relationship between high androgen activity and hy- with insulin resistance (hypertension, dyslipidemia, acan- perinsulinemia in women. To complete the circle, insulin thosis nigricans, or polycystic ovarian syndrome). Fasting resistance correlates strongly with the abdominal fat in obese plasma glucose is the primary screen to test for T2DM in adolescent girls. Insulin resistance stimulates ovarian as well young people. The 2-h blood glucose concentration after a as adrenal androgen and estrogen production. Obese females standard OGTT is more sensitive than plasma glucose in also have lower concentrations of SHBG with consequent assessing impaired glucose tolerance in youngsters, but it is further increase in the (free) biologically active fraction of the also more invasive, inconvenient, and expensive. Insulin re- sex hormones. These hormonal perturbations place the obese sistance is considered the greatest risk factor for the devel- adolescent girl at a high risk of menstrual disorders and early opment of T2DM. The homeostatic model assessment, which onset of polycystic ovarian syndrome. Weight loss induces a estimates insulin resistance, and the quantitative insulin- decrease in insulin resistance and androgenic activity, par- sensitivity check index, based on solely on fasting insulin and ticularly in adolescent girls with the abdominal pattern (76).
glucose, provide a crude, and not always reproducible, mea-sure of indices that are most accurately derived from the more invasive euglycemic and hyperglycemic clamp studies(67).
Heart disease. Obesity produces a variety of cardiac structuralchanges and hemodynamic alterations. Excessive adipose accumulation induces increased blood volume and cardiacoutput. Sleep apnea and obesity-related hypoventilation Metabolic changes seen in obese adults have been sum- may contribute to pulmonary arterial hypertension. In mor- marized under the so-called MS. The MS is defined differ- bid obesity these abnormalities may lead to a cardiomyop- ently according to different authorities. The U.S. National athy. Studies involving obese children and cardiovascular Cholesterol Education Program’s Adult Treatment Panel III risk are limited. The Bogalusa Heart Study indicated that (68) requires three of five characteristics: 1) abdominal obe- increased insulin and glucose levels in heavier children and sity given as waist circumference greater than 102 cm in men adolescents might be risk factors for increased left ventricular and greater than 88 cm in women; 2) hypertriglyceridemia mass corrected for growth (77). Childhood obesity does pre- with triglyceride concentration (Ն150 mg/dl or 1.7 mmol/ dispose to endothelial dysfunction, carotid intimal medial liter); 3) abnormal cholesterol profile with high-density li- thickening, and the development of early aortic and coronary poprotein (HDL) cholesterol less than 40 mg/dl or 1 mmol/ arterial fatty streaks and fibrous plaques (78). Whether child- liter in men and less than 50 mg/dl or 1.3 mmol/liter in hood obesity, like adult obesity, increases the risks of myo- women; 4) blood pressure: 130/85 mm Hg or more; 5) im- cardial infarction, stroke, and certain malignancies is cur- paired glucose tolerance, i.e. elevated fasting plasma glucose 100 mg/dl or 5.5 mmol/liter or more (69). The NationalCholesterol Education Program guidelines for adults have Hypertension. Hypertension occurs more commonly in obese been modified for adolescents such that triglycerides 110 persons at every age. Childhood obesity is the leading cause mg/dl or 1.2 mmol/liter or more are considered abnormal, of pediatric hypertension. Genetic, metabolic, and hormonal and the HDL threshold is set at 40 or less. Waist circumfer- factors such as insulin resistance, increased serum aldoste- ences 90% or more (from National Health and Nutrition rone levels, salt sensitivity, and possibly elevated leptin lev- Examination Surveys III) are considered abnormal, as are els are linked to the hypertension of obesity. Systolic blood blood pressures 90% or more (70). There is as yet no defi- pressure correlates positively with BMI, skinfold thickness, nition of the MS for the pediatric age group, but using adult and waist to hip ratio in children and adolescents (79).
criteria, the overall prevalence of MS among 12- to 19-yr-oldsin the United States was found to be 4.2% (70). Using mod- ified criteria, Weiss et al. (71) found that the risk of MS wasnearly 50% in severely obese youngsters, and risk increased Asthma and other respiratory problems. The association between asthma and overweight or obesity is debatable. One possible The WHO (72) and American Association of Clinical En- explanation for the apparent association between asthma docrinologists (73) criteria overlap the above but differ by and obesity is that both asthma and obesity share coincident requiring impaired fasting glucose, impaired glucose toler- increased prevalence. In obese people symptoms of breath- ance, or frank T2DM as defined on an OGTT. An added lessness and wheezing may be due to the increased work of diagnostic criterion of urinary albumin excretion rate greater breathing. Alternatively, obesity may have a direct effect on than 20 ␮g/min has been included in the WHO/American the mechanical behavior of the respiratory system by altering Association of Clinical Endocrinologists criteria.
compliance or elastic recoil, resulting in reduced effectivelung volume, airway caliber, or respiratory muscle strength In adolescent girls and young women, excess central or Sleep disorders. There is a strong association between obesity abdominal body fat is associated with hyperandrogenemia and obstructive sleep apnea (OSA) according to several co- (74). Sex hormone-producing enzymes are expressed in ad- hort studies (81). Obese children are 4 – 6 times more likely ipose tissue, and up to 50% of circulating testosterone may to have OSA, compared with lean subjects (82). OSA is di- J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity agnosed by an overnight sleep study to measure the apnea- though the prevalence of intracranial hypertension increases hypopnea index (AHI). An AHI of 5/h or more establishes up to 15-fold with increasing BMI, the risk of intracranial the diagnosis of OSA. Weight reduction is the preferred hypertension is increased even in persons who are only 10% modality to minimize AHI. OSA in adults has been related to the development of hypertension, cardiovascular diseases,behavioral disorders, and poor quality of life (83).
Prevention
Perinatal life: is there a need for preventive strategies in Nonalcoholic fatty liver disease. Obesity is associated with a Birth weight, postnatal weight gain, and subsequent obesity. Hu- spectrum of liver abnormalities, referred to as nonalcoholic man and animal data link the intrauterine environment to fatty liver disease. Characteristic biochemical findings in- postnatal health, with the underlying mechanisms still un- clude 4- to 5-fold elevations in hepatic transaminases, and 2- known. A U-shaped relationship exists between birth weight to 3-fold elevations in alkaline phosphatase and ␥ glutamyl and obesity in young adult life. Low birth weight owing to transpeptidase. Bilirubin, albumin, and prothrombin may maternal undernutrition, smoking, or placental insuffi- rise in later stages. The natural history varies according to ciency, or alternatively large size at birth attributable most histology: hepatic steatosis is frequently characterized by a often to GDM, may both be associated with obesity (89, 90).
benign clinical course without histological progression; how- Furthermore, the timing of prenatal nutritional deprivation ever, nonalcoholic steatohepatitis may become associated is apparently important in the future development of obesity, with increasing fibrosis and eventual rare cirrhosis (84).
as discerned in the study of Dutch men exposed to wartime Most children and adults are relatively asymptomatic.
famine (91). Obesity and ensuing metabolic complications Some individuals may have right upper quadrant pain, ab- often persist into middle age. Restricted prenatal growth dominal discomfort, weakness, fatigue, or malaise. Hepato- with rapid postnatal growth may be key to the early patho- megaly and stigmata of liver disease, such as palmar ery- genesis of adulthood disease. It is likely that genetic factors thema, vascular spiders, muscle wasting, jaundice, and in combination with intrauterine programming influence hepatic encephalopathy, may sometimes be present.
outcomes (92). As discussed above, breast-feeding is not Gallbladder disease. Obesity, MS, and hyperinsulinemia, or unconditionally protective for future obesity, although there alternatively rapid and significant weight loss are important risk factors for gallstone development (85). The mechanisms Proposed suggestions for preventing childhood obesity involved are not entirely clear. Early recognition of the se- beginning in prenatal life and throughout the life cycle at all verity of gall bladder disease is necessary for successful man- levels of society are shown in Table 3.
agement. Thus, gall bladder disease should be considered inthe differential diagnosis of persistent abdominal pain in How can we promote a healthy eating environment for children?Public health strategies to prevent obesity should begin with schools and extend to the entire community (93). Schools Overweight children are susceptible to developing bony must review their policies and procedures to promote deformities that can predispose them to other orthopedic healthy eating. This should include review of vending ma- problems later in life. Excess weight may cause injury to the chine offerings, food available in school cafeterias, and types growth plate and result in slipped capital femoral epiphysis, of food allowed for classroom events. A curriculum for nu- genu valga, tibia vara (Blount’s disease), flat kneecap pres- trition education to promote healthy eating habits, healthy sure/pain, flat foot, spondylolisthesis (low back pain), sco- body image, and weight management is essential from pre- school through high school. Healthy eating opportunitiesinclude affordable, palatable fresh fruits and vegetables and lower-fat food choices in school cafeterias and vending ma- Acanthosis nigricans, frequently found in young obese chines (94, 95). Regulatory agencies should ban advertising individuals, is characterized by hyperpigmented, hyperker- of fast foods directed at preschool children and restrict ad- atotic, velvety plaques on the dorsal surface of the neck, in the axillae, in body folds, and over joints. Severe skin changes How can we encourage physical activity? Lack of physical ac- correlate with elevated serum insulin levels and can be ame- tivity is not limited to inner-city populations but cuts across liorated by weight loss and consequent reduction in insulin socioeconomic, gender, and racial lines (96). A first step resistance. Other skin problems commonly encountered in- toward increasing activity is to restrict sedentary activities.
clude skin tags and keratosis pilaris (87).
Another crucial element for children is to make exercisereadily accessible at all ages in schools and residential areas.
Age-appropriate exercises should be fun, not punitive.
Obesity is associated with idiopathic intracranial hyper- Schools should mandate minimum standards for physical tension, or pseudotumor cerebri, manifested by headache, education, including 30 – 45 min of strenuous exercise two to vision abnormalities, tinnitus, and sixth nerve paresis. Al- Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 TABLE 3. Proposed suggestions for the prevention of obesity
Are screening programs indicated? The justification of any screening program is to improve important health outcomes 1. Normalize BMI prior to pregnancy.
with benefits that will outweigh inconvenience and cost and direct risks to the subjects. Screening programs for obesity 3. Maintain moderate exercise as tolerated.
and its complications would be justified if earlier interven- 4. In gestational diabetics, meticulous glucose control.
tion were shown to reduce morbidity and mortality. Several 1. Breast-feeding is preferred for a minimum of 3 months.
systematic reviews have examined the evidence regarding 2. Postpone introduction of solid foods and sweet liquids.
the benefits, limitations, and cost-effectiveness of a broad range of clinical preventive services for obesity (97). None of 1. Eat meals as a family in a fixed place and time.
the published trials has evaluated mass screening, but sur- 2. Do not skip meals, especially breakfast.
3. No TV during meals.
rogate measures, i.e. preventive strategies, have been exam- 4. Use small plates and keep serving dishes away from the ined. Firm evidence for the long-term effectiveness of any single preventive strategy in children is lacking (98). None- 5. Avoid unnecessary sweet or fatty foods and soft drinks.
theless, in the opinion of this group, primary care physicians 6. Remove televisions from children’s bedrooms; restrict times should screen all children for overweight and obesity. Ide- ally, where resources permit, children with BMI indicative of 1. Eliminate fundraisers with candy and cookie sales.
overweight status (i.e. Ͼ85th percentile by the U.S. CDC 2. Review contents of vending machines for healthier choices.
graphs or Ͼϳ91% by the European-Cole graphs) should receive weight management counseling, and those with obe- 4. Educate teachers, especially physical education and science faculty, about basic nutrition and benefits of physical activity.
sity, i.e. BMI at or above the 95th or 99% percentile in the 5. Educate children from preschool through high school on respective population graphs, should be screened for comor- bidities discussed above under Causes and Risks and referred 6. Mandate minimum standards for physical education, to appropriate specialists if these problems are detected.
including 30 – 45 min of strenuous exercise two to three timesweekly.
Treatment
7. Encourage “the walking schoolbus.” 1. Increase family-friendly exercise/play facilities for all age What is the rationale for early intervention? Obese children and 2. Discourage the use of elevators and moving walkways.
adolescents, like obese adults, are prone to develop many of 3. Provide information on how to shop and prepare healthier the comorbidities outlined above; they also suffer emotional versions of cultural-specific foods.
distress. The vulnerability of the obese child to serious com- 1. Explain biological and genetic noncontrollable contributions plications makes the case for prevention and treatment ir- refutable. Still there are some obese children and adults who 2. Give age-appropriate expectations for body weight in appear to suffer few or no metabolic complications (99); the factors that differentiate such subjects from other obese pa- 3. Work toward classifying obesity as a disease to promote recognition, reimbursement for care, and willingness and tients are currently unknown, and this is a fertile area for 1. Mandate age-appropriate nutrition labeling for products At what point does excess weight gain justify intervention? Recent aimed at children (e.g., red-light/green-light foods, with studies of American children and adolescents demonstrate that fasting serum glucose, insulin, triglycerides, C-reactive 2. Encourage marketing of interactive video games in which protein, and IL-6 concentrations and the prevalence of im- children must exercise in order to play.
paired glucose tolerance and systolic hypertension increase 3. Use celebrity advertising directed at children for healthful foods to promote breakfast and regular meals.
significantly with increasing obesity (BMI z score Ն 2), whereas HDL-cholesterol and adiponectin levels decline 1. Classify obesity as a legitimate disease.
(71). Even overweight children (BMI 85–95th percentile) are 2. Find novel ways to fund healthy lifestyle programs, i.e. with at increased risk for dyslipidemia and insulin resistance. In 3. Subsidize government-sponsored programs to promote contrast, rates of dyslipidemia, hypertension, and glucose consumption of fresh fruits and vegetables.
intolerance are low among children with BMI less than the 4. Provide financial incentives to industry to develop more 85th percentile for age. Thus, modified diets with decreased healthful products and to educate the consumer on product sedentary activities can be justified for children with BMI between the 85th and 95th percentiles, and more aggressive 5. Provide financial incentives to schools that initiate innovative physical activity and nutrition programs.
treatment should be directed toward children and adoles- 6. Allow tax deductions for the cost of weight loss and exercise cents with BMI at or above the 95th percentile (or z score Ն 2) or in less obese children who suffer metabolic, orthopedic, 7. Provide urban planners with funding to establish bicycle, or cardiopulmonary complications and/or psychological 8. Ban advertising of fast foods directed at preschool children, distress.
and restrict advertising to school-age children.
At what age should treatment begin? Most of the metaboliccomplications of childhood obesity emerge in adolescence J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity and young adulthood. However, five lines of evidence re- stigma of obesity treatment per se may be counterproductive viewed above suggest that intervention is warranted, even in obese children. First, severe obesity in toddlers and youngchildren is frequently accompanied by sleep apnea (82) and Dietary approaches. Mild caloric restriction is safe and can orthopedic anomalies (Blount’s disease) (86). Second, some be effective when obese children and their families are mo- obese children develop glucose intolerance, T2DM, dyslip- tivated and encouraged to change longstanding feeding be- idemia, and hypertension even before the onset of puberty haviors. An example of such a program aimed at families (71). Third, excessive weight gain between the ages of 2 and with children is the traffic light diet (105). Significant reduc- 10 yr increases the risks of adult obesity and glucose intol- tions in weight are unusual and often transient unless caloric erance, especially when the parents are obese and/or have restriction is accompanied by increased energy expenditure.
diabetes (12). Fourth, early vascular lesions have been de- Diets severely restricted in calories, including high-protein, tected in obese children as young as 3– 8 yr of age, suggesting very low-calorie diets, can facilitate more dramatic short- strongly that obesity-related atherogenesis begins in child- term weight loss. However, such diets cannot be sustained hood (78). Finally, intervention to prevent or reverse obesity under free-living conditions (106) and are potentially dan- in its early stages perhaps may be more successful and ben- gerous. Severe caloric restriction may cause deficiencies of eficial than treatment of established, severe obesity in ado- vitamins, minerals, and critical micronutrients; limit bone accretion and mineralization; reduce rates of linear growth;and disrupt menstrual cycles (107).
What are the goals of treatment? Goal setting and treatment of The role of specific dietary macronutrients in the patho- pediatric patients, many of whom are still growing, must be genesis and treatment of obesity is highly controversial. A individualized. The first goal is to restore the balance be- low-fat diet in combination with exercise and weight loss can tween energy intake and energy expenditure; in cases in reduce significantly the risks of T2DM and cardiovascular which intake is clearly excessive, it will be necessary to re- disease in adults with impaired glucose tolerance. Yet recent strict calories while increasing energy expenditure.
investigations showed that obese men and women lost more Stabilization of weight in growing children decreases BMI weight and had more significant reductions in plasma tri- z score slowly. Nevertheless, studies in adults suggest that glyceride concentrations on low-carbohydrate diets than on a 5–10% reduction in body weight at a rate of 0.5 kg/wk and conventional low-fat diets (108). A 3-month study in over- maintained over a period of 2–5 yr may increase insulin weight adolescents found similar effects (mean decrease in sensitivity and improve glucose tolerance (100) among other weight 9.9 kg in the low-carbohydrate group vs. 4.9 kg in the salutary changes. Thus, obese children (and their physicians) low-fat group); low-density lipoprotein (LDL) levels de- should be encouraged by any reduction in BMI z score. The clined with the low-fat diet but not with the low-carbohy- long-term objectives of treatment of childhood obesity are to drate diet (109). A review of adult studies suggests that the reduce BMI z score to less than 2 and reverse and prevent efficacy of low-carbohydrate diets may be related to overall caloric restriction rather than reduction in carbohydrate in-take per se. Moreover, the benefits of low-carbohydrate dietsmay diminish with time (110).
Limited evidence suggests that the nature or quality of Which treatment approach should be used first? ingested carbohydrate may modulate childhood weightgain. The insulin secretory response to foods containing rap- General considerations. The benefits of lifestyle intervention idly absorbed, concentrated carbohydrates (high glycemic are most likely to be achieved when diet and exercise pro- index) exceeds the response to foods containing high con- grams are coordinated with individual and family counsel- centrations of protein, fat, and fiber. Studies of the effects of ing and behavior modification (101). Long-term success re- glycemic index on weight gain in children are inconclusive.
quires continuous implementation; experience in adults Still, observations among adolescents have found that con- indicates that discontinuation of any therapeutic approach sumption of sugar-sweetened drinks is an independent vari- leads to rebound weight gain in the great majority of subjects.
able associated with increasing BMI (53, 111). In a separate Eating disorders and other psychiatric disorders are common study, a modified low-glycemic diet (45–50% carbohydrate, in obese subjects and must be addressed; otherwise, thera- 30 –35% fat) reduced BMI (Ϫ1.3 vs. 0.7 with a low-fat diet) and fat mass in obese adolescents (112). Thus, it appears that Parents provide a child’s contextual environment and thus elimination of carbonated drinks or other sugary drinks should be considered key players in interventions aimed at (juice and sports drinks) from the diet can significantly re- preventing or treating weight-related problems. Parenting duce caloric intake and obesity (113).
style and feeding style are crucial factors in fostering healthy Other macronutrients, vitamins, and trace elements may lifestyle and awareness of internal hunger and satiety cues modulate the risk of metabolic complications. For example, and deemphasizing thinness (102). In most family-based be- intake of fiber (particularly whole grains and cereal) corre- havioral weight-loss programs for children, the obese child lates inversely with the risks of T2DM and cardiovascular is the main target of change with varying degrees of parental disease (114). Insoluble and soluble fibers limit macronutri- involvement (103). Interestingly, recent reports suggest ent absorption and thereby increase fat oxidation and im- greater weight loss in obese children when parents alone are prove glucose tolerance. The intake of magnesium (from targeted for intervention (104). These data suggest that the whole grains, nuts, and green leafy vegetables) and dairy Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 products containing vitamin D and calcium may also cor- success of lifestyle intervention alone has been disappoint- relate inversely with the risks of obesity and T2DM in chil- ing. For example, in an Italian multicenter study of nutri- tional intervention in 1383 obese pediatric patients, drop-outrates ranged from 30 –34% after 3 months to 90 –94% after 2 Exercise. A sedentary lifestyle increases the risks of child- yr (120). Noncompliance was highest in the most obese chil- hood obesity and predisposes to diabetes and cardiovascular dren. A Cochrane review of randomized, controlled trials of disease, whereas exercise, in combination with caloric and fat duration 6 months or more (n ϭ 18 studies, 975 participants) restriction, reduces the rate of progression to diabetes in concluded that most studies are too small to detect effects of adults with impaired glucose tolerance and limits cardio- treatment, and few trials use the same comparisons and vascular morbidity and mortality. The benefits of exercise are outcomes (103). Thus, the data are of limited quality.
mediated, at least in part, by reductions in total and visceralfat stores and increases in lean body mass, which augmentresting energy expenditure (116). Exercise enhances adipose tissue sensitivity to insulin; reduces fasting and postprandial If supervised lifestyle intervention fails, the patient should free fatty acid, LDL, and triglyceride concentrations; and be referred to a subspecialist for evaluation. The subspecialist increases plasma HDL levels. The heightened sensitivity to should assess the extent and magnitude of comorbidities and insulin and induction of fatty acid oxidation enhance vas- may consider more intensive therapeutic approaches includ- ing pharmacotherapy. Current pharmacologic interventions Available evidence, albeit limited, suggests that exercise are designed to increase energy expenditure (stimulants), can benefit obese children and reduce the risks of metabolic suppress caloric intake (anorectic agents), limit nutrient ab- and cardiovascular complications. A randomized, modified sorption and/or modulate insulin production and/or action.
cross-over study of 79 obese children (aged 7–11 yr) dem-onstrated that 4 months of exercise training (40 min of ac- Stimulants. The use of metabolic stimulants for the treatment tivity 5 d/wk) reduced percent body fat (5%) and decreased of obesity has a checkered history. Many antiobesity drugs fasting insulin (10%) and triglyceride (17%) concentrations, once considered safe and effective, i.e. thyroid hormone, even in the absence of dietary intervention (118). Additional dinitrophenol, amphetamine, fenfluramine, dexfenflura- uncontrolled trials suggest that aerobic exercise can also im- mine, phenylpropanolamine, and ephedra, have been aban- prove vascular endothelial function (119). The benefits of doned because they caused dangerous and in some cases exercise are quenched or reversed rapidly if activity is not A single short-term trial compared caffeine plus ephedrine The capacity for voluntary exercise declines as BMI rises.
with placebo in adolescents taking a mildly hypocaloric diet.
It is therefore critical to begin regular exercise before the child Although the drug-treated subjects lost more weight, ad- becomes morbidly obese and functionally immobile. A sum- verse effects were more frequent (121). These agents cannot mary of proposed suggestions for basic lifestyle intervention in children is provided in Table 4. The Cochrane study con- Anorectic agents. The only anorectic agent currently approved cluded that “there are limited high-quality data on the ef- for use in obese adolescents (older than 16 yr) is sibutramine, fectiveness of obesity prevention programs, and no gener- a nonselective inhibitor of neuronal reuptake of serotonin, alizable conclusions can be drawn. However, concentration norepinephrine, and dopamine. In combination with caloric on strategies that encourage reduction in sedentary behav- restriction and a comprehensive family-based behavioral iors and increase in physical activity may be fruitful” (98).
program, sibutramine reduced BMI 8.5 Ϯ 6.8% in 43 obese Thus, lack of formal evidence does not preclude action.
adolescents during an initial 6-month period; a 4.0 Ϯ 5.4% Diet and exercise regimens may prove effective for short- reduction in BMI was achieved in 39 placebo-treated subjects term treatment of pediatric obesity. However, the long-term (122). No additional weight loss occurred during a subse-quent 6 months of therapy. Fasting insulin concentrations TABLE 4. Basic treatment interventions: lifestyle changes
declined and HDL levels increased. However, 19 of 43 sub-jects treated with sibutramine developed mild hypertension and tachycardia, necessitating reduction in drug dose, and 1. Eliminate all sugary drinks (including juice), and replace with water, noncaloric beverages, and lowfat or skim milk.
five had sustained elevations in blood pressure that required 2. Restrict calories enough to produce mild negative energy discontinuation of the drug. Other potentially serious com- plications include insomnia, anxiety, headache, and depres- 3. Reduce intake of saturated fats, salty snacks, and high sion. There is a heightened risk of the serotonin syndrome if glycemic foods including candy, white bread, white rice, sibutramine is used in combination with monoamine oxidase 4. Create a balanced diet containing vegetables, fruits, whole inhibitors, buspirone, lithium, or meperidine, or selective grains, nuts, fiber, lean meat, fish and low-fat dairy products.
serotonin reuptake inhibitors, such as fluoxetine, triptans, dextromethorphan, ergot alkaloids, or fentanyl.
1. Exercise should be fun, age-specific, and tailored to the child’s Anorectic agents should complement, never replace, a diet 2. Involve large muscle groups to increase energy expenditure.
and exercise program. The drugs have modest effects on total 3. Increase frequency, intensity, and duration with time.
body weight (typically an additional 2–10 kg in obese adults), 4. Restrict sedentary behaviors: television viewing, video games, and responses vary considerably among individuals. Most of the weight loss from anorectic agents is achieved within the J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity first 4 – 6 months of treatment due to the achievement of a second trial (n ϭ 24), in conjunction with a low-calorie diet, negative plateau; regain of weight is the norm unless drug metformin reduced weight 2.7% relative to controls and de- therapy is maintained. Administration of this drug is not creased plasma leptin, insulin, glucose, cholesterol, and tri- recommended for more than 2 yr duration.
Leptin treatment has been given to children with genetic Metformin is generally well tolerated, although many pa- leptin deficiency resulting in dramatic weight reduction (26), tients have transient abdominal discomfort, avoidable by taking but it is doubtful that individuals with nonleptin-deficient the medication with food. Lactic acidosis is extraordinarily rare forms of obesity will benefit from similar treatment.
in pediatric patients, but metformin should not be administeredto children with underlying cardiac, hepatic, renal, or gastro- Drugs that limit nutrient absorption. The drug orlistat inhibits intestinal disease. Obese subjects with mild elevations in he- pancreatic lipase and thereby increases fecal losses of tri- patic enzymes (less than 3-fold higher than established norms) glyceride. Orlistat decreases body weight and total and LDL may receive the drug; indeed, some studies suggest that met- cholesterol levels and reduces the risk of T2DM in adults formin may be useful in treatment of hepatic steatosis. Con- with impaired glucose tolerance. In the United States, orlistat current use of a multivitamin is warranted because metformin is currently approved by the Food and Drug Administration increases urinary excretion of vitamins B in children older than 12 yr. In obese adolescents, the com- approved by the Food and Drug Administration for treatment bination of orlistat with lifestyle intervention reduced weight of T2DM but not currently for treatment of childhood obesity (Ϫ4.4 Ϯ 4.6 kg), BMI (Ϫ1.9 Ϯ 2.5 kg/m2), total cholesterol (Ϫ21.3 Ϯ 24.7 mg/dl or 0.55 Ϯ 0.64 mmol/liter), LDL(Ϫ17.3 Ϯ 15.8 mg/dl or 0.45 Ϯ 0.41 mmol/liter), fasting Octreotide. Octreotide binds to the somatostatin-5 receptor insulin (Ϫ13.7 Ϯ 19.0 ␮U/ml or 95.1 Ϯ 132.0 pmol/liter), and and thereby impairs closure of the ␤-cell calcium channel, fasting glucose (Ϫ15.4 Ϯ 7.4 mg/dl or 0.85 Ϯ 0.41 mmol/ reducing glucose-dependent insulin secretion. In a double- liter) concentrations and increased insulin sensitivity during blind, placebo-controlled trial in children with hypothalamic a 3-month trial period (123). There was considerable vari- obesity, octreotide reduced insulin secretory responses and ability in response to the drug. Variable reductions in body rates of weight gain (ϩ1.6 Ϯ 0.6 vs. ϩ9.2 Ϯ 1.5 kg) and BMI weight (Ϫ12.7 Ϯ 2.5 kg) and fat mass were also noted in a (Ϫ0.2 Ϯ 0.2 vs. ϩ2.3 Ϯ 0.5 kg/m2) (126). The cost of the study of 11 morbidly obese children aged 7–12 yr. Side effects medication, the need for parenteral administration, and the are tolerable as long as subjects reduce fat intake, but vitamin drug’s side effects, which may include transient gastrointes- A, D, and E levels may decline despite multivitamin sup- tinal distress, gallstones, suppression of GH and TSH secre- plementation. High study dropout rates (25% or more) sug- tion, and cardiac dysfunction, limit its current applicability gest that long-term fat restriction is problematic in teenagers; to patients with intractable obesity from hypothalamic dietary noncompliance results in flatulence and diarrhea that Insulin sensitizers and suppressors. The synthesis and storageof triglyceride in adipose tissue are stimulated by insulin.
The long-term success of lifestyle intervention and pharma- Thus, increases in nutrient-dependent insulin production cotherapy in subjects with severe obesity has in general been and/or fasting hyperinsulinemia may contribute to fat stor- disappointing. Marked weight loss is highly unusual and rarely age and limit fat mobilization. By reducing fasting or post- sustained, and metabolic and vascular complications are com- prandial insulin concentrations, certain pharmacologic mon, albeit not universal. More aggressive approaches such as agents may prove beneficial in the treatment of obese chil- bariatric surgery may be indicated in selected subjects with dren and adults. In this drug class, only metformin treatment extreme obesity and serious comorbidities. The surgical ap- proaches now used most commonly are the laparoscopic gastricbanding procedure and the Roux-en-Y gastric bypass (RYGB).
Metformin. Metformin is a bisubstituted, short-chain hydro- Gastric banding may cause esophageal dilatation and philic guanidine derivative that activates AMP protein ki- achalasia and may exacerbate gastroesophageal reflux. Other nase. Its major site of action is the liver: the drug increases potential complications include port site malposition or mal- hepatic glucose uptake, decreases gluconeogenesis, and re- function, balloon rupture, and infection. Complications of duces hepatic glucose production. Major advantages of the RYGB include iron-deficiency anemia (50%); folate, thia- drug include decreased food intake, weight loss, decreased mine, or calcium deficiencies (at least 30%); cholecystitis fat stores (sc more than visceral), improved lipid profiles, and (20%); wound infections and dehiscence (10%); small bowel a reduction in conversion to T2DM among adults with im- or stomach obstruction (5–10%); atelectasis and pneumonia (12%); and incisional hernia (10%). Prophylactic tracheos- There have been two randomized, double-blind, placebo- tomy may be required to maintain airway patency and cor- controlled studies of metformin in obese adolescents with rect preoperative hypercapnia. Other possible complications insulin resistance, normal glucose tolerance, and a positive include leaks at the anastomotic junction, gastric dilatation, family history of type 2 diabetes. In the first trial (n ϭ 29), and dumping syndrome. Among the most serious compli- metformin reduced BMI z score (3.6% relative to placebo cations are potentially fatal pulmonary emboli. Mortality controls), plasma leptin, and fasting glucose (Ϫ9.8 mg/dl or rates for RYGB range from 1 to 5%. Complication rates may 0.54 mmol/liter) and insulin (Ϫ12 ␮U/ml or 83.3 pmol/ be reduced if bariatric procedures are performed through liter), even in the absence of dietary intervention (124). In the laparoscopy by an experienced surgeon. There have been Speiser et al. • Childhood Obesity J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 relatively few published surgical trials pertaining to adoles- Who should receive intensive evaluation and treatment? In most cents (127, 128); however, the outcomes seem to parallel cases, the primary care physician will be responsible for bariatric surgery performed in adults (129) and warrant fur- management of overweight infants and children. Clearly the burden is too large to be borne by specialty physicians. It isvery important for primary care physicians to recognize in-dividual overweight patients and intervene before they be- come obese (132). Basic dietary advice should be provided in How should the clinician balance lifestyle intervention, pharma- the primary care setting. This should include elimination of cotherapy, and surgery in the treatment of obesity? Lifestyle all sweetened beverages, including juices, caloric carbonated intervention is indicated for all overweight and obese chil- drinks, iced tea, and lemonade; use of low-fat or fat-free milk dren and should be maintained, even if more aggressive/ in children over the age of 2 yr; portion control; increased fruit and vegetable intake; reduction in fast food consump- Pharmacotherapy may be considered for complicated obe- tion; and counseling about the need for daily vigorous ex- sity in peripubertal children or adolescents who fail to re- ercise. Weekly office weigh-ins can monitor home progress, spond to at least a 6-month trial of supervised lifestyle in- and if this is deemed insufficient, the child should be seen by tervention despite good faith effort. The term complicated a registered dietitian or enrolled in a formal weight-man- obesity implies the presence of major comorbidities includ- agement program. Patients who have unusual distinguish- ing glucose intolerance, hypertension, dyslipidemia, sleep ing characteristics may require a specialist’s consultation.
apnea, or other comorbidities discussed above. Failure to There are several examples of these characteristics. First, respond means that the comorbidities persist or worsen de- infants who have rapid weight gain and abnormally low spite lifestyle intervention. Good faith effort means the pa- linear growth are likely to have an underlying disease. In tient has attempted to follow dietary recommendations and addition, infants with syndromic features, neurological def- has increased energy expenditure through regular exercise.
icits, or abnormal fat distribution associated with obesity Given its efficacy in treating obese, insulin-resistant ado- lescents, its track record of safety, and its ability to limit food In addition, children and adolescents who meet the criteria intake and weight gain, the authors consider metformin the for obesity (BMI Ͼ 95%) and those with eating disorders drug of choice for treating the obese adolescent with severe should be referred for expert evaluation and intervention.
insulin resistance or glucose intolerance.
Children with an early age of adiposity rebound (the period Anorectic agents such as sibutramine should not be ad- when the BMI begins to increase after reaching a nadir in ministered to prepubertal children. Use of this drug in any- early childhood) are at highest risk for overweight, later one under age 16 yr remains experimental and should be glucose intolerance, and diabetes (133). These children also undertaken only in specialized pediatric treatment centers in need a thorough clinical evaluation.
the context of clinical trials approved by institutional review As genotype-phenotype knowledge increases, lifestyle, boards. Neuropsychologic testing before and during therapy pharmacologic, and surgical therapies may be applied more may be warranted. Inhibitors of nutrient absorption such as orlistat are not tolerated by many obese children but mightbe applied successfully in selected, highly motivated pa- Where should delivery of advanced care be centered? Obese pa- tients. The use of octreotide for treatment of hypothalamic tients with comorbidities such as sleep apnea, glucose intoler- obesity, although promising, remains experimental. Other ance, hypertension, nonalcoholic steatohepatitis, polycystic medications are in phase III studies in obese adults (reviewed ovarian syndrome, and dyslipidemia will require the expertise in Ref. 131) but will not be available for children for several of subspecialists in pediatric endocrinology, gastroenterology, nutrition, cardiology, exercise and sports medicine, pulmonary Firm or uniform guidelines regarding duration of phar- medicine, orthopedics, and behavioral medicine; their efforts macologic treatment are not feasible at this time. A trial off must be coordinated within the setting of specialized obesity medication may be warranted if comorbidities are reversed, clinics. Until a safe and effective treatment can be recommended particularly if there has been a significant decline in BMI z for severely obese children, intensive inpatient treatment ap- score. In all cases, pharmacotherapy should be discontinued proaches should remain an option in specialized centers for if the patient fails to respond to the drug.
limited durations in the context of a comprehensive, long-term Bariatric surgery should be reserved for treatment of ad- management program. The intensive therapies that have been olescents with extreme obesity (usually defined as BMI Ͼ 40 used to treat pediatric and adolescent obesity include very or Ͼ 35 with established comorbidities) who have failed low-calorie diets, pharmacotherapy, and bariatric surgery. Psy- other treatment approaches. Surgery should be performed chosomatic units specializing in the treatment of eating disor- only under the rubric of clinical trials in medical centers that ders are the logical choice by providing a milieu for the obese have expertise in bariatric surgical techniques and are sup- children and adolescents with life-threatening medical compli- ported by multidisciplinary teams with long-standing expe- cations. Such programs adhere to recommendations of the Ex- rience in the evaluation and management of obese children.
pert Committee on Obesity Evaluation and Treatment for an Contraindications to bariatric surgery include substance effective behavioral and nutritional approach for child obesity abuse or psychiatric disabilities (including severe eating dis- (134). These include a group format with individualized be- orders) that prevent lifelong compliance with nutritional havioral counseling, intensive family involvement and training, recommendations or medical surveillance (127, 128).
behavior modification targeted at changing home and family J Clin Endocrinol Metab, March 2005, 90(3):1871–1887 Speiser et al. • Childhood Obesity TABLE 5. Summary of proposals
Clinical overweight: BMI at or above 85th centileClinical obesity: BMI Ͼ 95th centile on national charts (99th centile on UK charts)Epidemiological or international studies: IOTF cutoffs Action is required antenatally, in schools, community facilities, marketing, government and regulatory Population screening is required to identify overweight children with BMI Ͼ 85th centile Laboratory assessment of children above 95th centile should include: a) Thyroid and liver function tests, fasting glucose, insulin and lipid profile.
b) Children at increased risk for the metabolic syndrome require periodic oral glucose tolerance tests from c) Screening for other comorbidities: e.g., hypertension, sleep apnea, orthopedic problems, etc.
Children with BMI at or above 85th centile should receive regular lifestyle counseling.
Children with BMI Ͼ 95th centile require specialist pediatric care.
Children with comorbidity or severe obesity should receive their care in a multidisciplinary specialist lifestyle, moderated caloric restriction targeted at inducing phasized as the safest means for primary care physicians to modest (5–10%) weight reduction associated with improve- manage patients. The decision of when to intervene with ment of medical complications, a physical activity program pharmacotherapy or bariatric surgery must be made for chil- emphasizing choice and reinforcing reduced sedentary behav- dren and adolescents on a case-by-case basis, according to the iors, skills for managing high-risk situations, and skills for guidelines presented above. To date, although somewhat encouraging, only limited and short-term evidence is avail-able to support the use of selected drugs or surgical proce- Conclusions
dures to alleviate morbid obesity in this population. Longer- In the foregoing pages, we have described the problems term clinical trials with larger numbers of children and associated with childhood obesity, providing strong evi- adolescents will be required before drug treatment or sur- dence that adult morbidities may begin in early life. Perhaps gical intervention can be routinely employed.
because of the rapid evolution of these problems, publicpolicy makers have not yet taken action to address existing Acknowledgments
and future repercussions. Obesity is now a major contribut- The following participants convened in Ein Bokek, Dead Sea, Israel, ing factor to increasing rates of disability among adults (135).
March 24 –27, 2004, and contributed to this manuscript: R. Bahar-Einav, Health care costs of patients with a BMI greater than 35 are D. Bass-Rotenstein (Pittsburgh, PA); Z. Bistrizer (Zerifin, Israel); G. Brill, approximately 44% more than those of nonobese patients.
E. Leiberman, Y. Limoni (Beersheva, Israel); S. Chalew (New Orleans, Furthermore, it is well established that the health care costs LA); J. Dahlgren (Gotheburg, Sweden); M. Golan, A. Hanukoglu, A.
of treating patients with T2DM, a common sequel of obesity, Zung (Rehovot, Israel); A. Golander, E. Gur, A. Kochli, Z. Laron, D.
Levin, Y. Meirovitch, D. Modan-Mozes, N. Leventhal, Zohar Landau, E.
are substantially higher than treatment for patients without Zubery (Tel Aviv, Israel); H. Guttman, I. Koren, Y. Levy, D. Tiosano diabetes. This should provide incentive for the private and (Haifa, Israel); H. Hirsch, H. Landau, D. Zangen (Jerusalem, Israel); L.
public sectors to: 1) mobilize all available resources to stem Karaviti (Houston, TX); A. Kurtev (Sofia, Bulgaria); M. Lampit (Zefat, the tide of increasing body mass in children and adults, 2) Israel); I. Poraz (Petah Tikva, Israel); Y. Rakover (Afula, Israel); T. J.
Rozenberg (Jerusalem, Israel); J. Popovic (Kansas City, MO); C. Silver- classify obesity as a disease, paving the way for public fund- stein, S. Ten (Brooklyn, NY); R. Weiss (New Haven, CT); and O. Yogev ing and ensurers’ reimbursement for obesity treatment pro- grams, and 3) spur further research to more effectively pre- The working group also acknowledges the contributions of: N. Dixit vent and treat obesity. Precedents for successful public (Tucson, AZ); L. Edmunds (Bristol, UK); C. Maffeis and L. Tato` (Verona, health campaigns include those designed to stem tobacco Italy); and A. Vargas (New Orleans, LA).
use, prevent the spread of HIV, and promote the use seat Received July 15, 2004. Accepted December 1, 2004.
belts in motor vehicles and bicycle helmets in children. Pro- Address all correspondence and requests for reprints to: Phyllis W.
fessional societies (especially those dedicated to primary care Speiser, M.D., Division of Pediatric Endocrinology, Schneider Children’s and endocrinology), health care providers, and educators Hospital, 269-01 76th Avenue, New Hyde Park, New York 11040. E-mail: should assume leadership roles in achieving these goals (23).
The work for the Consensus Conference was supported by Aventis, The WHO has formulated a plan to tackle obesity, and the Ben Gurion University, Ferring Pharmaceuticals, Israel Society for Pe- IOTF has created a credentialing system for obesity special- diatric Endocrinology, Eli Lilly Co., Novo Nordisk, Pfizer, Roche, and ists and treatment centers. In the United States, the Depart- ment of Health and Human Services recently convened anObesity Summit to discuss the best means of addressing this References
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Document is provided for sample purposes only. Content is not updated and should not be used for traveler counseling. LEPTOSPIROSIS INTRODUCTION Leptospirosis is an acute zoonotic illness caused by spirochetes belonging to the genus Leptospira and which occursthroughout the world. A vast range of animals, including amphibians, reptiles, and mammals, can become infected andbecome reservoir

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1 IDENTIFICATION OF THE SUBSTANCE/PREPARATION AND OF THE COMPANY/UNDERTAKINGAgropharm LimitedBuckingham Place,Church Road, Penn,High WycombeBucksHP10 8LNTel: +44 (0) 1494 816575Factory: +44 (0)1952 740333Fax: +44 (0) 1494 816578sales@agropharm.co.ukVery toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment. CLASSIFICATIONThe Full Text for all R-Phrases are

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