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.
CHILDHOOD OBESITY 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 Abstract 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) A 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 250 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. 1999;282:1523–1529. 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 content.healthaffairs.org/cpi/reprint/hlthaff.w3.219.v1. 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- 69,70 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. 2008;152:191–200. 19. Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wat- References tigney WA: Association between multiple cardiovascular risk fac- 1. CDC Obesity by State Maps, www.cdc.gov/obesity/data/trends. tors and atherosclerosis in children and young adults. New England html. Accessed September 1, 2010. Journal of Medicine. 2009;338:1650–1656. 2. Flegal KM, Carroll MD, Ogden CL, Curtin LR: Prevalence 20. Kortelainen ML: Adiposity, cardiac size and precursors of coronary and trends in obesity among U.S. adults, 1999–2008. JAMA. atherosclerosis in 5 to 15-year-old children: A retrospective study of 2010;303:235–241. 210 violent deaths. Int J Obes Relat Metab Disord. 1997;21:691–697. 3. Haslam DW, James WP: Obesity. Lancet. 2005;366:1197–1209. 21. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS: The 4. Hossain P, Kawar B, El Nahas M: Obesity and diabetes in the relation of overweight to cardiovascular risk factors among chil- developing world: A Growing Challenge. New England Journal of dren and adolescents: The Bogalusa Heart Study. Pediatrics. Medicine. 2009;356:213–215. 1999;103:1175–1182. CHILDHOOD OBESITY October 2010 255 22. Guillaume M, Lapidus L, Beckers F, Lambert A, Bjorntorp P: Car- 40. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier diovascular risk factors in children from the Belgian province of NF, O’Connor GT, Boland LL, Schwartz JE, Samet JM: Sleep- Luxembourg. The Belgian Luxembourg Child Study. Am J Epide- disordered breathing and cardiovascular disease: Cross-sectional miol. 1996;144:867–880. results of the Sleep Heart Health Study. Am J Respir Crit Care 23. Morrison JA, Barton BA, Biro FM, Daniels SR, Sprecher DL: Med. 2001;163:19–25. Overweight, fat patterning, and cardiovascular disease risk factors 41. Punjabi NM, Beamer BA: Alterations in glucose disposal in sleep- in black and white boys. J Pediatr. 1999;135:451–457. disordered breathing. Am J Respir Crit Care Med. 2009;179:235– 24. Eva O, Colin OW, Jeffrey AC, Rae-Ellen WK, Gail DP, Stephen 240. RD: Prevalence and incidence of hypertension in adolescent girls 42. Reichmuth KJ, Austin D, Skatrud JB, Young T: Association of (Abstract). The Journal of pediatrics. 2010;157:461–467. sleep apnea and type II diabetes: A population-based study. Am J Respir Crit Care Med. 2005;172:1590–1595. 25. Chen X, Wang Y: Tracking of blood pressure from childhood to adulthood: A systematic review and meta-regression analysis. Cir- 43. Manoff EM, Banffy MB, Winell JJ: Relationship between body culation. 2008;117:3171–3180. mass index and slipped capital femoral epiphysis. J Pediatr Orthop. 2005;25:744–746. 26. Ford ES, Li C, Zhao G, Mokdad AH: Concentrations of low-fensity lipoprotein cholesterol and total cholesterol among children and 44. Benson EC, Miller M, Bosch P, Szalay EA: A new look at the inci- adolescents in the United States. Circulation. 2009;119:1108–1115. dence of slipped capital femoral epiphysis in New Mexico. J Pedi- atr Orthop. 2008;28:529–533. 27. Bao W, Srinivasan SR, Wattigney WA, Bao W, Berenson GS: Use- fulness of childhood low-density lipoprotein cholesterol level in 45. Murray AW, Wilson NI: Changing incidence of slipped capital predicting adult dyslipidemia and other cardiovascular risks. The femoral epiphysis: A relationship with obesity? J Bone Joint Surg Bogalusa Heart Study. Arch Intern Med. 1996;156:1315–1320. Br. 2008;90:92–94. 28. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury 46. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, PR, Zeitler P: Increased incidence of non-insulin-dependent diabe- Bhapkar MV, Koch GG, Hasemeier CM: Secondary sexual charac- tes mellitus among adolescents. J Pediatr. 1996;128:608–615. teristics and menses in young girls seen in office practice: A study from the Pediatric research in office settings network. Pediatrics. 29. Dabelea D, Bell RA, D’Agostino RB, Jr., Imperatore G, Johansen 1997;99:505–512. JM, Linder B, Liu LL, Loots B, Marcovina S, Mayer-Davis EJ, Pettitt DJ, Waitzfelder B: Incidence of diabetes in youth in the 47. Kaplowitz PB: Link between body fat and the timing ofpuberty. United States. JAMA. 2007;297:2716–2724. Pediatrics. 2008;121:S208–S217. 30. Pavkov ME, Bennett PH, Knowler WC, Krakoff J, Sievers ML, 48. Wang Y: Is obesity associated with early sexual maturation? A comparison of the association in American boys versus girls. Pedi- Nelson RG: Effect of youth-onset type 2 diabetes mellitus on atrics. 2002;110:903–910. incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA. 2006;296:421–426. 49. Kousta E: Premature adrenarche leads to polycystic ovary syndrome? Long-term consequences. Ann N Y Acad Sci. 31. Chan DF, Li AM, Chu WC, Chan MH, Wong EM, Liu EK, Chan 2006;1092:148–157. IH, Yin J, Lam CW, Fok TF, Nelson EA: Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord. 2004;28:1257– 50. Denzer C, Weibel A, Muche R, Karges B, Sorgo W, Wabitsch M: 1263. Pubertal development in obese children and adolescents. Int J Obes. (Lond) 2007;31:1509–1519. 32. Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC, Brunetti F, Rubino A: Liver involvement in obese 51. Lee JM, Kaciroti N, Appugliese D, Corwyn RF, Bradley RH, children. Ultrasonography and liver enzyme levels at diagno- Lumeng JC: Body mass index and timing of pubertal initiation in sis and during follow-up in an Italian population. Dig Dis Sci. boys. Arch Pediatr Adol Med. 2010;164:139-144. 1997;42:1428–1432. 52. Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, 33. Strauss RS, Barlow SE, Dietz WH: Prevalence of abnormal serum Dandona P: Frequent occurrence of hypogonadotropic hypogonad- aminotransferase values in overweight and obese adolescents. J ism in type 2 diabetes. J Clin Endocrinol Metab. 2004;89:5462– Pediatr. 2000;136:727–733. 5468. 34. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Beh- 53. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomain- ling C: Prevalence of fatty liver in children and adolescents. Pedi- en TP, Valkonen VP, Salonen R, Salonen JT: Testosterone and sex atrics. 2006;118:1388–1393. hormone-binding globulin predict the metabolic syndrome and dia- betes in middle-aged men. Diabetes Care. 2004;27:1036–1041. 35. Loomba R, Sirlin CB, Schwimmer JB, Lavine JE: Advances 54. Moriarty-Kelsey M, Harwood JE, Travers SH, Zeitler P, Nadeau in pediatric nonalcoholic fatty liver disease. Hepatology. KJ: Testosterone, obesity and insulin resistance in young males: 2009;50:1282–1293. Evidence for an association between gonadal dysfunction and insu- 36. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, lin resistance during puberty. Journal of Pediatric Endocrinology Schork NJ, Lavine JE: Histopathology of pediatric nonalcoholic and Metabolism. (In press). fatty liver disease. Hepatology. 2005;42:641–649. 55. Sun SS, Liang R, Huang TT, Daniels SR, Arslanian S, Liu K, 37. Lee TH, Kim WR, Benson JT, Therneau TM, Melton LJ, III: Serum Grave GD, Siervogel RM: Childhood obesity predicts adult aminotransferase activity and mortality risk in a United States com- metabolic syndrome: The Fels Longitudinal Study. J Pediatr. munity. Hepatology. 2008;47:880–887. 2008;152:191–200. 38. Arens R, Muzumdar H: Childhood obesity and obstructive sleep 56. Mattsson N, Ronnemaa T, Juonala M, Viikari JS, Raitakari OT: apnea syndrome. J Appl Physiol. 2010;108:436–444. Childhood predictors of the metabolic syndrome in adulthood. The 39. Verhulst SL, Schrauwen N, Haentjens D, Suys B, Rooman RP, cardiovascular risk in young Finns study. Ann Med. 2008;40:542– Van GL, De Backer WA, Desager KN: Sleep-disordered breath- 552. ing in overweight and obese children and adolescents: prevalence, 57. Morrison JA, Glueck CJ, Horn PS, Wang P: Childhood predictors characteristics and the role of fat distribution. Arch Dis Child. of adult type 2 diabetes at 9- and 26-year follow-ups. Arch Pediatr 2007;92:205–208. Adolesc Med. 2010;164:53–60. 256 MORIARTY-KELSEY AND DANIELS 58. Mahoney LT, Burns TL, Stanford W, Thompson BH, Witt JD, Rost CA, 66. Baker JL, Olsen LW, Sorensen TI: Childhood body-mass index Lauer RM: Coronary risk factors measured in childhood and young and the risk of coronary heart disease in adulthood. N Engl J Med. adult life are associated with coronary artery calcification in young 2007;357:2329–2337. adults: The Muscatine Study. J Am Coll Cardiol. 1996;27:277–284. 67. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, 59. Davis PH, Dawson JD, Riley WA, Lauer RM: Carotid intimal- Looker HC: Childhood obesity, other cardiovascular risk fac- medial thickness is related to cardiovascular risk factors measured tors, and premature death. New England Journal of Medicine. from childhood through middle age: The Muscatine Study. Circula- 2010;362:485–493. tion. 2001;104:2815–2819. 68. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, 60. Raitakari OT, Juonala M, Viikari JS: Obesity in childhood and vas- Brody J, Hayflick L, Butler RN, Allison DB, Ludwig DS: A poten- cular changes in adulthood: Insights into the cardiovascular risk in tial decline in life expectancy in the United States in the 21st cen- young Finns study. Int J Obes. (Lond) 2005;29 Suppl 2:S101–S104. tury. N Engl J Med. 2005;352:1138–1145. 61. Urbina EM, Gidding SS, Bao W, Pickoff AS, Berdusis K, Berenson 69. Daviglus ML, Liu K, Pirzada A, Yan LL, Garside DB, Feinglass J, GS: Effect of body size, ponderosity, and blood pressure on left Guralnik JM, Greenland P, Stamler J: Favorable cardiovascular risk ventricular growth in children and young adults in the Bogalusa profile in middle age and health-related quality of life in older age. heart study. Circulation. 1995;91:2400–2406. Arch Intern Med. 2003;163:2460–2468. 62. Gunnell DJ, Frankel SJ, Nanchahal K, Peters TJ, vey Smith G: 70. Lloyd-Jones DM, Leip EP, Larson MG, D’Agostino RB, Beiser Childhood obesity and adult cardiovascular mortality: A 57-y A, Wilson PW, Wolf PA, Levy D: Prediction of lifetime risk for follow-up study based on the Boyd Orr cohort. Am J Clin Nutr. cardiovascular disease by risk factor burden at 50 years of age. Cir- 1998;67:1111–1118. culation. 2006;113:791–798. 63. Lawlor DA, Martin RM, Gunnell D, Galobardes B, Ebrahim S, Sandhu J, Ben-Shlomo Y, McCarron P, vey Smith G: Association of body mass index measured in childhood, adolescence, and young Address correspondence to: adulthood with risk of ischemic heart disease and stroke: Findings Stephen R. Daniels, MD, PhD from 3 historical cohort studies. Am J Clin Nutr. 2006;83:767–773. Professor and Chairman 64. Lawlor DA, Leon DA: Association of body mass index and obesity measured in early childhood with risk of coronary heart disease and Department of Pediatrics stroke in middle age: Findings from the Aberdeen children of the University of Colorado School of Medicine 1950s prospective cohort study. Circulation. 2005;111:1891–1896. The Children’s Hospital 65. Osler M, Lund R, Kriegbaum M, Andersen AM: The influence of 13123 E. 16th Avenue, B065 birth weight and body mass in early adulthood on early coronary Aurora, CO 80045 heart disease risk among Danish men born in 1953. Eur J Epide- miol. 2009;24:57–61. Email: Daniels.email@example.com
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