Childhood Obesity is the Fuel That Fires Adult Metabolic Abnormalities and Cardiovascular Disease

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Childhood Obesity is the Fuel That Fires Adult Metabolic Abnormalities and Cardiovascular Disease Powered By Docstoc
October 2010 | Volume 6, Number 5
                                                                                                      REVIEW ARTICLE
© Mary Ann Liebert, Inc.
DOI: 10.1089/chi.2010.0504

          Childhood Obesity Is the Fuel That Fires
               Adult Metabolic Abnormalities
                and Cardiovascular Disease
                            Megan Moriarty-Kelsey, MD and Stephen R. Daniels, MD, PhD

  The prevalence of obesity has been increasing in both adults and children, in the U.S. and worldwide. Because obesity is associ-
ated with numerous complications such as heart disease, diabetes, and certain cancers, its burden on the healthcare system is enor-
mous. There is increasing evidence that obesity tracks over time from childhood to adulthood and, because the prevalence is rising
in children, this will have significant impact on the burden that its complications will carry in the future. Obese children already
demonstrate markers for cardiovascular disease, such as insulin resistance, hypertension, hypercholesterolemia and the metabolic
syndrome. Furthermore, diseases such as type 2 diabetes and fatty liver disease, which were previously thought to be diseases of
adulthood, have become increasingly prevalent in the pediatric population. Obesity also has implications which are unique to child-
hood, such as increased incidence of slipped capital-femoral epiphysis and disordered pubertal development. Not only is obesity
associated with higher rates of cardiovascular risk factors in childhood, but there is emerging evidence that obese children have
increased risk for cardiac events and early mortality as adults. The impact of this is that life expectancy could be reduced for the first
time. There is evidence that maintaining low risk for cardiovascular disease decreases morbidity and mortality from this common
disease. Therefore, early prevention of and early intervention for childhood obesity should be an important focus to minimize future
disease burden.

Introduction                                                               Complications of obesity are numerous and include:
                                                                        cardiovascular disease (CVD), type 2 diabetes (T2DM)

         s is well illustrated by the ever-changing obesity             and gestational diabetes, certain cancers, decreased fertil-
         prevalence maps published by the Center for Dis-               ity, osteoarthritis, sleep apnea, liver disease, and gallblad-
         ease Control (CDC), obesity—defined as BMI                     der disease.5 Furthermore, obesity can lead to a decreased
> 30 kg/m2—has been increasing in adults by alarming                    quality of life, social stigmatization and discrimination.
rates over the past several decades. 1 According to the                 The cost of obesity and its complications is enormous.
most recently published National Health and Nutrition                   According to a cost analysis based on expenditures from
Examination Survey (NHANES) data, 32.2.% of Ameri-                      1996–1998, 9.1% of U.S. medical expenditures (up to
can men and 35.5% of American women were obese in                       $78.5 billion) in 1998 were attributable to obesity. About
2007–2008 and 68% and 72.3%, respectively, were at                      half of these costs were paid for by Medicare and Med-
least overweight. 2 These rates were stable in women,                   icaid, demonstrating the economic burden on the U.S.
who have a higher overall obesity prevalence, compared                  population as a whole. This does not account for the asso-
with the last survey (1999–2000), but continue to rise in               ciated cost of lost work time and decreased productivity.6
men. The increase in obesity is not unique to the U.S.                     The prevalence of obesity in children has been rising in
The World Health Organization estimated that, in 2005,                  parallel with that of adults, with the prevalence of obesity
1.7 billion adults were overweight and 312 million were                 (defined as BMI > 95th percentile for age and sex) in the
obese worldwide.3 The prevalence of obesity tripled in                  U.S. more than doubling since the 1980s.7 According to
the past 20 years in countries that have adopted a Western              the most recent NHANES data (2007–2008), approxi-
lifestyle and, although the poorest countries still struggle            mately 17% of children and adolescents aged 2–19 are
with under-nutrition, being poor in a middle-income                     obese and 32% are overweight (BMI > 85th percentile for
country is actually associated with increased risk for obe-             age and sex).8 These prevalences differ by race/ethnicity:
sity.4                                                                  Hispanic boys are more likely to be obese than non-His-

University of Colorado School of Medicine, Department of Pediatrics

CHILDHOOD OBESITY October 2010                                                                                        251

panic white boys and non-Hispanic black girls are more         of 357 adolescents who had euglycemic clamps as a
likely to be obese than non-Hispanic white girls. Not only     measure of insulin sensitivity at multiple time points,
is obesity increasing in prevalence, but it is also increas-   insulin resistance at age 13 years was a strong predic-
ing in severity. In fact, among the 17% of children and        tor of higher systolic blood pressure and triglycerides,
adolescents who are obese in the U.S., more than 70%           which are both components of the metabolic syndrome,
fall into the highest BMI category of > 97%. Again, child-     at age 19 years.16 This demonstrates a similar relation-
hood obesity is not a problem that is unique to the U.S.;      ship of insulin resistance to metabolic syndrome in
it is estimated that approximately 110 million children        the pediatric population. The clustering of risk factors
worldwide are overweight or obese and that 20 million of       seen in metabolic syndrome has been demonstrated to
these children are under the age of 5 years.8                  affect up to 39% of moderately obese and up to 50% of
   Whereas it was previously thought that most over-           severely obese children and adolescents.17 Furthermore,
weight children would “grow into” their weight during          large epidemiological studies have demonstrated child-
puberty, there is now increasing evidence that overweight      hood obesity to be a strong predictor of adult metabolic
children become overweight adults. A review of the litera-     syndrome.18 The impact of early metabolic syndrome on
ture published in 1993 suggested that 42–63% of obese          future cardiac events has yet to be elucidated.
school children become obese adults, such that obese
school children have four times greater risk of becom-         Other markers for cardiovascular risk
ing obese adults compared with non-obese children.9 In            Autopsy studies of adolescents have demonstrated pres-
a study of Danish draftees born between 1930 and 1956,         ence of early atherosclerosis, and the degree of disease is
those with an adult BMI > 31 kg/m2 had a higher BMI            strongly associated with obesity.19,20 In adults, hyperten-
at age 7 years when compared with a random sample of           sion and elevated low-density lipoprotein (LDL) cho-
the adult population.10 Although these studies primarily       lesterol are associated with atherosclerosis, and there is
include populations of European descent, data from the         some evidence from autopsy studies that this also may be
Bogalusa Heart Study, a large cohort of non-Hispanic           the case in adolescents.19 Multiple studies have demon-
whites and blacks, suggests similar trends in other races.11   strated a relationship between obesity and hypertension in
Out of 783 adolescents (age 13–17 years) who were              children and adolescents and prevalence of hypertension
also studied as young adults (age 27–31 years) the risk        in children appears to be rising in parallel with increasing
of remaining overweight was 52% and 62% in African-            rates of obesity.21–23 One recent study of 2368 Caucasian
American males and females, respectively. Overall in           and African-American girls who were studied longitudi-
this cohort, there was a positive correlation between BMI      nally from age 9–10 years until 18–19 years, reported a
at age 9-11 years with BMI at age 19–35 years (r=0.66,         prevalence of hypertension of 1–2% in African-American
p<0.0005) and approximately 62% in the highest quartile        girls and 0.5% in Caucasian girls. The prevalence of
in childhood remained there as a young adult.
                                                               hypertension was 6 times as likely in obese girls as in
                                                               girls of normal weight.24 Furthermore, childhood hyper-
Immediate Impact of Childhood                                  tension has been shown to track into adulthood, similar
                                                               to other risk factors for CVD and to obesity itself. In a
Obesity: Markers of Cardiovascular Risk                        recent meta-analysis of 50 studies evaluating tracking of
Insulin resistance/metabolic syndrome                          hypertension from childhood to adulthood, the average
  Multiple studies have demonstrated that obese ado-           correlation coefficient for blood pressure tracking was
lescents are more insulin resistant than their lean peers,     0.38 for systolic and 0.28 for diastolic blood pressure.
using several different techniques for assessing insulin       The relationships strengthened with older age at initial
resistance, including the gold-standard hyperinsulinemic       assessment and with shorter follow-up time. There were
euglycemic clamp technique. 12–14 Insulin resistance is        no differences in tracking among race/ethnicity varia-
not only a marker of risk for development of T2DM, but         tion.25
is also associated with presence of the metabolic syn-            According to NHANES data based on the years 1999–
drome and increases the risk for CVD. The metabolic            2006, between 5.2% and 6.6% of children aged 6–17
syndrome is a cluster of risk factors that, in adults, is      years were estimated to have elevated LDL cholesterol26
known to increase risk for development of CVD. There           which, as noted previously, has been associated with
are several widely accepted definitions in adults, which       increased atherosclerosis in children in autopsy studies.
generally include a combination of elevated triglycer-         Furthermore, data from the Bogalusa Heart Study, which
ides, low high-density lipoprotein (HDL) cholesterol,          followed 1169 5–14 year-olds for a period of 15 years,
high blood pressure, increased waist circumference             show a strong correlation between childhood and adult-
and/or elevated fasting glucose.15 Multiple definitions        hood LDL cholesterol (r= 0.4–0.6). Additionally in this
of metabolic syndrome exist in pediatrics; however,            cohort, elevated childhood LDL cholesterol was a predic-
unlike in adults, they are based on percentiles for risk       tor of low HDL, high triglycerides, obesity and hyperten-
factors, not on disease outcomes. In a longitudinal study      sion in adulthood.27
252                                                                                MORIARTY-KELSEY AND DANIELS

Adult Diseases in Childhood                                    is based on histopathology from liver biopsy samples and
                                                               clinical non-invasive markers, such as elevated alanine
   Another immediate impact of the increasingly high           aminotransferase and ultrasound findings which have
prevalence of childhood obesity is that diseases that were     poor sensitivity and specificity; therefore, it is a difficult
previously limited to onset in adulthood are now affecting     diagnosis to make and likely is often missed. Many chil-
the pediatric population, including T2DM and nonalco-          dren with NASH display histopathology that is unique
holic steatohepatitis (NASH). The prevalence of T2DM           from typical adult NASH.35 One recent study of pediatric
in youth is difficult to ascertain, although it is certainly   patients with NASH reported that only 17% had features
on the rise. For example, data from Cincinnati indicate a      entirely consistent with adult, or Type 1, NASH.36 The
tenfold increase in T2DM from 0.7 per 100,000 to 7.2 per       remainder had histopathology that appears to be unique to
100,000 between 1982 and 1994, such that it accounted          the pediatric population (Type 2) or a mixture of the two
for 16% of all new cases of diabetes in 1994, compared         types of histopathology. The impact of Type 2 histopatho-
with 2–4% of new cases in the 12 preceding years.28 Per-       logical features on prognosis and treatment is still unclear.
haps the most accurate and compelling U.S. prevalence          In adults, suspected fatty liver disease (as estimated by
data for T2DM come from the SEARCH for Diabetes in             elevated ALT) is associated with increased mortality
Youth Study.29 SEARCH is a multi-center longitudinal           from cardiovascular disease and other causes.37 However,
observational study attempting to ascertain incidence of       because this is a new diagnosis in pediatrics, the long-term
diabetes in several geographic regions, healthcare plan        clinical implications are not known.
groups and American Indian reservation populations and            Like adults, obese children also have increased risk
covers over 10,031,888 person-years at risk. According         for respiratory problems, including sleep apnea and
to SEARCH, T2DM rarely affects children under the age          decreased exercise tolerance. Obstructive sleep apnea
of 10 years; with 96% of incident cases being reported         syndrome (OSAS) leads to hypoxemia and poor sleep
in youth aged 10–19. The highest rates were reported in        quality at night and, therefore, increased fatigue during
American Indians (49.4 per 100,000 person-years in ages        the day. Obesity is postulated to be the most common
15–19), followed by African American, Asian/Pacific            cause of OSAS in children.38 Like some non-obese chil-
Islander, and Hispanic youth; the lowest rates were
                                                               dren with OSAS, obese children with OSAS tend to have
reported in non-Hispanic whites (5.6 per 100,000 person-
                                                               tonsillar and adenoid hypertrophy.39 However, their OSAS
years in ages 15–19). It is more common in female than
                                                               is less likely to resolve after adenotonsillectomy. 38 In
in male youths (RR=1.63, p<0.001). Although type 1
                                                               adults, obesity-associated OSAS has been associated with
diabetes accounts for a much greater proportion of dia-
                                                               increased coronary artery disease, congestive heart failure
betes overall in youth aged 0–19, according to SEARCH
                                                               and stroke.40 Furthermore, there is increasing evidence
estimates, T2DM accounts for more than 50% of diabetes
                                                               that OSAS may be a causal factor in the development of
cases in African Americans, Asian/Pacific Islanders, and
                                                               insulin resistance and hypertension.41,42 Although obese
American Indians aged 10–19 years, and almost 50% of
                                                               children with OSAS are too young to develop CVD, they
diabetes in Hispanics of the same age group. Although the
                                                               still have increased risk factors for CVD and clinical
impact this will have on early-onset diabetes complica-
                                                               features of insulin resistance. Therefore, pediatric OSAS
tions is not yet known, emerging evidence suggests that it
                                                               may again be indicative of long-term adverse outcomes,
will be important. For example, in a recent study of Pima
Indians, the incidence of end-stage renal disease was 25       in addition to its immediate detrimental effects.
cases per 1000 person-years in those with onset of T2DM
at <20 years versus 5.4 cases per 1000 person-years in         Problems Unique to Childhood
those with older-onset diabetes.30 Furthermore, death rates
were three times higher in those with youth-onset T2DM           In addition to effects on early development of CVD risk
than those without diabetes.                                   factors and adult obesity-associated diseases, there are
   The spectrum of fatty liver diseases, which ranges from     aspects of obesity, such as increased risk of slipped capi-
simple steatosis to fulminant non-alcoholic steatohepa-        tal femoral epiphysis (SCFE) and alterations in pubertal
titis (NASH), is also becoming more common in obese            development, that are unique to the pediatric population.
children. It is estimated that anywhere between 10% and        SCFE involves displacement of the femoral epiphysis
77% of obese children have fatty liver.31–33 A recent study    and is the most common hip disorder of adolescence.
of 742 autopsy studies of children aged 2–19 revealed that     If left untreated, it has long-term consequences, includ-
13% of them had steatosis.34 The estimated population          ing degenerative joint disease and avascular necrosis. It
prevalence based on this study is 9.6%, making it the most     is known to be associated with overweight. One recent
common cause of liver disease in children. Furthermore,        case-control study of 106 subjects with radiographic dem-
23% of those with steatosis had NASH, which can prog-          onstration of SCFE and 46 subjects without, found that
ress to cirrhosis and hepatocellular carcinoma. It appears     81% of cases were obese, as opposed to 41% of controls
to be more common in older children (15–19 years),             (p<0.0001).43 Furthermore, as might be expected, multiple
males, and in Asians and Mexican Americans. Diagnosis          studies have confirmed a rising incidence of SCFE in
CHILDHOOD OBESITY October 2010                                                                                          253

parallel with the rising rates of obesity in children.44,45 Not     These large cohort studies have also evaluated the
only does SCFE contribute to both short- and long-term            effects of childhood obesity on noninvasive markers of
costs of obesity treatment, but also further impairs exer-        CVD in adulthood, such as coronary artery calcification
cise capacity in affected obese children.                         and carotid intimal medial thickness (IMT). In a total
   The observation that pubertal onset is occurring at            of 384 subjects from the Muscatine Study evaluated for
younger ages in females in the past several decades was           coronary calcification (CAC) in their late 20s/early 30s,
reported as early as 1997.46 The earlier age of pubertal          high BMI at an average age of 15 years was strongly
onset appears to coincide with the increasing prevalence          associated with CAC. The odds ratio for CAC for those
of obesity.47 Girls from the NHANES cohort who matured            in the highest childhood BMI decile was 6.4 for men and
earlier had a greater BMI than late-onset girls. 48 The           13.4 for women.58 In a larger representative cohort from
PROS study, which was specifically designed to assess             the same study, higher childhood BMI was predictive of
pubertal timing in females, similarly found a correlation         higher carotid IMT in women but not in men at age 33–42
between breast Tanner stage and BMI z-score in a given            years.59 Adult carotid IMT, measured in 2,283 subjects
age group. 46 Furthermore, premature adrenarche (as               aged 24–39 years, was also found to be strongly associ-
opposed to central precocious puberty), is also more com-         ated with childhood BMI in the Cardiovascular Risk in
mon in obese females and is associated with increased             Young Finns Study. 60 Finally, in a 4-year longitudinal
risk for Polycystic Ovary Syndrome (PCOS).49                      follow-up study of 160 children from the Bogalusa heart
   Data on effects of obesity on male pubertal develop-           study, baseline ponderal index (at an average age of 13.3
ment are limited. Several recent studies have suggested           years) was a strong predictor of growth in left ventricular
that pubertal onset and/or development may be delayed             mass at follow up.61
in obese boys.48,50,51 Whereas obese adult females with             Results from large retrospective cohort studies regard-
PCOS have increased androgen production, obesity and              ing outcomes, such as cardiac events and mortality, are
insulin resistance have been associated with hypogo-              somewhat mixed. Fifty-seven year follow up of the Boyd
nadism in adult males.52,53 One recent study of adoles-           Orr cohort, which consisted of 2,399 children aged 2 to
cent males suggests that boys who are obese and those             14 years 9 months, suggested that those with a BMI >75th
who have T2DM have lower testosterone concentra-                  percentile had a hazard ratio of 1.5 for all-cause mortality
tions than their lean counterparts.54 Furthermore, higher         and 2.0 for ischemic heart disease when compared with
BMI and greater insulin resistance (as measured by                those with a BMI between the 25th and 49th percentile.62
euglycemic clamp) were both independently associated              However, when this cohort was combined with two other
with lower testosterone. Because testosterone affects             historical cohorts, no association was found between
development of lean muscle mass, early development                BMI and future risk of mortality from ischemic heart
of hypogonadism in obese males may have detrimental               disease and stroke.63 Data from the Aberdeen Children of
effects of whole-body insulin sensitivity and on exer-            the 1950s cohort study, in which subjects had height and
cise capacity.                                                    weight measured at an average age of 4.9 years and were
                                                                  followed by a Scottish register that began tracing morbid-
                                                                  ity in 1981, suggest no association between BMI at age
Long-Term Outcomes                                                4.9 years and future coronary heart disease or stroke.
   Because childhood obesity has only recently begun to           However, those who were obese in childhood did have
affect a large proportion of the worldwide population,            increased risk of stroke in adulthood.64 Two Danish cohort
effects of pediatric obesity on cardiac events in adult-          studies did find a strong association between obesity at a
hood are difficult to assess. Longitudinal studies such as        young age and risk for adult cardiovascular disease. One
the Muscatine, Fels and Bogalusa studies, provide some            study included 9,143 men, who were born in 1953 and
evidence regarding effects of childhood obesity on adult          had a health examination at an average age of 19 years. In
metabolic syndrome and other markers of risk for CVD.             this cohort, those with a BMI great than 30 kg/m2 at age
Analysis of 743 subjects with and without the metabolic           19 had a hazard ratio of 2.48 when compared with those
syndrome from the Fels Longitudinal Study, suggests               with a BMI of <20 kg/m2. Furthermore, the BMI hazard
that the odds ratio for metabolic syndrome as an adult for        ratio was 1.25 for each unit increase in BMI z-score.65 In
boys with an elevated BMI at age 14–18 years is 1.8 and           another Danish registry cohort study of 276,835 school-
for obese girls in the same age group is 2.8.55 Similarly, in     children for whom height and weight data were avail-
the Cardiovascular Risk in Young Finns Study, a prospec-          able, and included a total of 5,063,622 person-years of
tive cohort study including 2,195 subjects at baseline (age       follow-up, risk of both fatal and nonfatal coronary heart
3–18 years), youth BMI >80th percentile for age and sex           disease events was positively associated with BMI at age
was found to be the strongest predictor of adult metabolic        7 to 13 years for males and 10 to 13 years for females.66
syndrome.56 In 822 subjects evaluated in the Princeton            Finally, Franks et al recently reported some compelling
Follow-up Study, childhood BMI in the top 5th percentile          prospective data regarding premature death (before age
was a strong predictor of T2DM at age 39 years.57                 55 years) based on a cohort of 4,857 American Indians
254                                                                                        MORIARTY-KELSEY AND DANIELS

without diabetes, who were born between 1945 and 1981.             5. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH:
These children had a baseline assessment of BMI at age                 The disease burden associated with overweight and obesity. JAMA.
11.3 years and, during a median follow-up period of 23.9
                                                                   6. Finkelstein EA, Fiebelkorn IC, Wang G: National medical spending
years, those with a baseline BMI in the highest quartile               attributable to overweight and obesity: How much, and who’s pay-
had more than twice the risk for premature endogenous                  ing? Health Aff. 2003: Suppl Web Exclusives:W3-219-26. http://
death as those in the lowest baseline BMI quartile.67         Accessed
                                                                       August 18, 2010.
                                                                   7. Ogden CL, Flegal KM, Carroll MD, Johnson CL: Prevalence and
Conclusions                                                            trends in overweight among U.S. children and adolescents, 1999–
                                                                       2000. JAMA. 2002;288:1728–1732.
   It is quite clear that the prevalence and severity of           8. Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM: Preva-
obesity have increased dramatically in children and ado-               lence of high body mass index in U.S. children and adolescents,
lescents. This is already creating increased obesity in the            2007–2008. JAMA. 2010;303:242–249.
adult population and may lead to further increases in the          9. Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF,
future. While long term data are few, the available data               Byers T: Do obese children become obese adults? A review of the
suggest that these trends in obesity will result in increased          literature. Preventive Medicine. 1993;22:167–177.
morbidity and mortality due to diabetes and cardiovascular         10. Sorensen TI, Sonne-Holm S: Risk in childhood of development of
disease in the future for adults who began their obesity in            severe adult obesity: Retrospective, population-based case-cohort
                                                                       study. Am J Epidemiol. 1988;127:104–113.
childhood. If the analyses of Olshansky et al which predict
                                                                   11. Srinivasan SR, Bao W, Wattigney WA, Berenson GS: Adolescent
outcomes based on known relationships of obesity to car-               overweight is associated with adult overweight and related multiple
diovascular disease and other risks68 are correct, this will           cardiovascular risk factors: The Bogalusa Heart Study. Metabolism.
lead to a decline in life expectancy and potentially dramatic          1996;45:235–240.
increases in healthcare costs in the United States.                12. Ball GD, Weigensberg MJ, Cruz ML, Shaibi GQ, Kobaissi HA,
   An important concept to understand is that these out-               Goran MI: Insulin sensitivity, insulin secretion and beta-cell func-
comes are preventable. A variety of studies, including the             tion during puberty in overweight Hispanic children with a fam-
                                                                       ily history of type 2 diabetes. International Journal of Obesity.
Framingham Study, now demonstrate that maintaining                     2005;29:1471–1477.
optimal levels of cardiovascular risk factors including            13. Moran A, Jacobs DR, Jr., Steinberger J, Hong CP, Prineas R, Luep-
BMI throughout childhood into adulthood and up to age                  ker R, Sinaiko AR: Insulin resistance during puberty: Results from
50 years is associated with a very low risk of cardiovas-              clamp studies in 357 children. Diabetes. 1999;48:2039–2044.
cular morbidity and mortality throughout the rest of life.         14. Nadeau KJ, Ehlers L, Draznin B, Regensteiner J, Reusch J: Exer-
      The problem is that the prevalence of maintaining                cise capacity is abnormal in youth with type 2 diabetes. Diabetes.
such low risk status to age 50 in our current environment              2007;56:Supp 1:A278.
is only about 5%.69,70 This defines our challenge for the          15. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Frank-
future. We must seek effective ways for children and ado-              lin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Jr., Spertus
                                                                       JA, Costa F: Diagnosis and management of the metabolic syndrome:
lescents to maintain a normal BMI and optimal CVD risk                 An American Heart Association/National Heart, Lung, and Blood
status and then continue this through young adulthood.                 Institute Scientific Statement. Circulation. 2005;112:2735–2752.
This primordial prevention holds tremendous promise                16. Sinaiko AR, Steinberger J, Moran A, Hong CP, Prineas RJ, Jacobs
to decrease the burden of cardiovascular disease and                   DR, Jr.: Influence of insulin resistance and body mass index at age
improve the quality of life for many in the United States.             13 on systolic blood pressure, triglycerides, and high-density lipo-
These efforts must begin with children.                                protein cholesterol at age 19. Hypertension. 2006;48:730–736.
                                                                   17. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel
                                                                       CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS,
                                                                       Caprio S: Obesity and the metabolic syndrome in children and ado-
Disclosure Statement                                                   lescents. N Engl J Med. 2004;350:2362–2374.
The authors have no competing financial interests to declare.      18. Sun SS, Liang R, Huang TT, Daniels SR, Arslanian S, Liu K,
                                                                       Grave GD, Siervogel RM: Childhood obesity predicts adult
                                                                       metabolic syndrome: The Fels Longitudinal Study. J Pediatr.
                                                                   19. Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wat-
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Description: The prevalence of obesity has been increasing in both adults and children, in the U.S. and worldwide. Because obesity is associated with numerous complications such as heart disease, diabetes, and certain cancers, its burden on the healthcare system is enormous. There is increasing evidence that obesity tracks over time from childhood to adulthood and, because the prevalence is rising in children, this will have significant impact on the burden that its complications will carry in the future. Obese children already demonstrate markers for cardiovascular disease, such as insulin resistance, hypertension, hypercholesterolemia and the metabolic syndrome. Furthermore, diseases such as type 2 diabetes and fatty liver disease, which were previously thought to be diseases of adulthood, have become increasingly prevalent in the pediatric population.