CLINICAL REPORT

Guidance for the Clinician in Rendering Pediatric Care

The Metabolic Syndrome in Children Sheela N. Magge, MD, MSCE, FAAP,​a Elizabeth Goodman, MD, MBA, FAAP,b​ Sarah C. Armstrong, andMD, FAAP,c​ COMMITTEE Adolescents: ON NUTRITION, SECTION ON ENDOCRINOLOGY, Shifting SECTION ON OBESITY the Focus to Cardiometabolic Risk Factor Clustering Metabolic syndrome (MetS) was developed by the National Cholesterol abstract Education Program Adult Treatment Panel III, identifying adults with at least 3 of 5 cardiometabolic risk factors (hyperglycemia, increased central adiposity, elevated triglycerides, decreased high-density lipoprotein cholesterol, and elevated blood pressure) who are at increased risk of aDivision of Endocrinology and Diabetes, and Center for Translational Science, Children's National Health System, Washington, District of diabetes and cardiovascular disease. The constellation of MetS component Columbia; bDepartment of Pediatrics, Harvard Medical School, Boston, risk factors has a shared pathophysiology and many common treatment Massachusetts; and cDuke Children’s Hospital and Health Center, Durham, North Carolina approaches grounded in lifestyle modification. Several attempts have been Dr Magge served as the lead author and organized the writing and made to define MetS in the pediatric population. However, in children, the revising efforts of the team, conceptualized and drafted the initial construct is difficult to define and has unclear implications for clinical care. manuscript, and critically reviewed the revised manuscript; Drs Goodman and Armstrong conceptualized and drafted the initial In this Clinical Report, we focus on the importance of screening for and manuscript and critically reviewed the revised manuscript; and all treating the individual risk factor components of MetS. Focusing attention authors approved the final manuscript as submitted. on children with cardiometabolic risk factor clustering is emphasized over This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have the need to define a pediatric MetS. filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. Introduction Clinical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent. Cardiovascular disease (CVD) risk factor clustering has been well The guidance in this report does not indicate an exclusive course of recognized for decades in both children and adults, but it was not treatment or serve as a standard of medical care. Variations, taking “ ” into account individual circumstances, may be appropriate. until 1988 when Gerald Reaven described a specific clustering of “ ” ’ All clinical reports from the American Academy of Pediatrics cardiometabolic risks as syndrome X that the concept that evolved automatically expire 5 years after publication unless reaffirmed, into the metabolic syndrome (MetS) was born. Reaven s syndrome revised, or retired at or before that time. X was an explanatory framework to understand the myriad effects of hyperinsulinemia and insulin resistance on physiology, not a diagnostic 1 To cite: Magge SN, Goodman E, Armstrong SC, AAP category. His formulation of syndrome X described mechanisms COMMITTEE ON NUTRITION, SECTION ON ENDOCRINOLOGY, underlying insulin resistance and the effects of hyperinsulinemia on SECTION ON OBESITY. The Metabolic Syndrome in Children glucose and lipid metabolism, blood pressure, and coronary artery and Adolescents: Shifting the Focus to Car­diometabolic disease risk. Over time, the risk factors associated with syndrome X Risk Factor Clustering. Pediatrics. 2017;140(2):e20171603 grew to include other factors, such as central obesity,1,2​ microalbuminuria, abnormalities in fibrinolysis, and inflammation. ‍ Dissemination of the Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017:e20171603 FROM THE AMERICAN ACADEMY OF PEDIATRICS concept of syndrome X promulgated used, there is no uniform way to lipoprotein cholesterol, and the idea of insulin resistance causing treat MetS when it is diagnosed increased small, dense18 low-density a constellation of factors that other than weight management. lipoprotein particles,​ which are increased diabetes and CVD’ risk. Instead, each risk factor must be known to be atherogenic and to treated individually, which leaves increase cardiovascular risk. After publication of Reaven s pediatricians wondering whether landmark article, clustering of One of the major clinical they should (and how to) define CVD risks was variously described consequences of insulin resistance MetS in their patients. Our purpose “ ” as insulin resistance syndrome, is adipose tissue dysfunction, or with this Clinical Report is to provide syndrome X, and the dysmetabolic adiposopathy. As adipose expands, an overview of the current state syndrome. In 2001, the National the cells hypertrophy, and these of the field in relation to MetS in ’ Cholesterol Education Program hypertrophic adipose cells are “ pediatric populations. Given its name (NCEP) Adult Treatment Panel III more resistant to insulin s action ” recognition, MetS terminology will (ATP III) coined the term metabolic to suppress lipolysis. These large be used in this report. However, syndrome to describe the presence adipocytes also secrete increased the clinical relevance of MetS of any 3 of 5 particular risks: proinflammatory chemokine lies in its ability to be used as an hyperglycemia, hypertriglyceridemia, monocyte chemoattractant organizational framework for the 19 central adiposity, elevated blood protein-1. As stated previously, identification of cardiometabolic risk pressure, and low high-density insulin action stimulating fatty acid factor clustering. Recommendations lipoprotein cholesterol (HDL-C). synthesis is preserved, promoting for pediatricians regarding how Research on MetS has increased adipose tissue expansion. MetS is to approach the concept of MetS dramatically since 2001, with more characterized by increased visceral in children and adolescents are than 1000 articles per year published as opposed to subcutaneous fat provided. on this topic since 2006. MetS has as well as ectopic fat deposited in 6 been associated with both diabetes Pathophysiology abnormal locations, such as the liver. and CVD in adults. Insulin resistance, Ectopic fat distribution results in the obesity, aging, inflammation, release of adipocytokines, causing a hormonal factors, sedentary lifestyle, state of low-grade inflammation, with The pathophysiologic origins of dietary sugar intake, and genetics increased inflammatory factors, such – MetS are in insulin resistance, a α all have been implicated in the as plasminogen activator inhibitor-1, 1 6 physiologic state associated with pathogenesis of MetS. ‍‍ tumor necrosis factor , interleukin obesity. Insulin binds to receptors 6, and acute phase reactants such as Despite this vast literature, MetS on multiple tissues of the body, high-sensitivity C-reactive protein remains a controversial topic in including liver, fat, muscle, and blood 20 and fibrinogen. The endoplasmic pediatrics for several reasons. First, vessels, with a myriad of effects (Fig β reticulum acts as a nutrient sensor. MetS is challenging to define in 1). Insulin secreted by the pancreatic Energy or nutrient excess can pediatric populations. MetS in adults cells travels to the liver via the trigger endoplasmic reticulum consists of a subset of at least 3 out portal system, where it normally stress, resulting in activation of of 5 risk factors: increased central acts to suppress glucose production. inflammatory pathways, increased adiposity, elevated triglycerides, In the insulin-resistant state, the reactive oxygen species production, decreased HDL-C, elevated blood suppression of hepatic glucose 21 and mitochondrial dysfunction. pressure, and hyperglycemia. In production is impaired, resulting Some emphasize the importance of adults, MetS (the presence of 3 or in abnormal glucose homeostasis. the inflammatory state, with insulin more of these risks) is predictive of However, even in an insulin-resistant 3,7​ “ ” resistance being a consequence of CVD and type 2 diabetes mellitus. ‍ state, not all insulin effects are 20 inflammation. Irrespective of what In children and adolescents, however, impaired; there is selective insulin 17 is the consequence or cause, insulin many different definitions of MetS resistance. For unknown reasons, resistance, ectopic fat distribution, have been proposed (Table 1), and insulin action stimulating hepatic and inflammation are all key there is no clear consensus on which lipogenesis is not impaired, causing 8,9​ pathologic players in the components to use. In addition, because the the release of free fatty acids and of MetS. majority of MetS cases in childhood triglycerides into the circulation. Defining MetS in Adults and adolescence occur in individuals This results in dyslipidemia6 and with obesity, the utility of MetS– as a ectopic adipose deposition. The construct above and beyond8,10​ obesity12 MetS dyslipidemia pattern consists of itself has been questioned. ‍ ‍‍ elevated triglycerides, low HDL-C, At least 5 health organizations Regardless of the definition relatively normal low-density have created clinical criteria for Downloaded from www.aappublications.org/news by guest on September 26, 2021 e2 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Comparison of Key Published MetS Definitions for Pediatric and Adult Populations Pediatric Definitions Adult Definitions Cook et al13 de Ferranti et al14 Zimmet et al9 (IDF Alberti et al15 (IDF Definition Grundy et al16 (AHA/NHLBI Definition Ages Ages 16+) Consensus Statement) 10–16) Defining criterion ≥3 criteria ≥3 criteria Obesity and at least Obesity and at least 2 of ≥3 criteria 2 of remaining 4 remaining 4 criteria criteria Obesity WC ≥90th percentile WC >75th percentile WC ≥90th percentile WC ≥94 cm for white men WC ≥102 cm (≥40 in) in men and (age and sex or adult cutoff if and ≥80 cm for white WC ≥88 cm (≥35 in) in women specific, NHANES lower women III) Glucose intolerance Fasting glucose Fasting glucose Fasting glucose Fasting glucose ≥100 mg/dL Fasting glucose ≥100 mg/dL or ≥110 mg/dL (≥6.1 ≥110 mg/dL (≥6.1 ≥100 mg/dL (>5.6 (>5.6 mmol/L) or known drug treatment of elevated mmol/L) mmol/L) mmol/L) or known type 2 diabetes mellitus glucose type 2 diabetes mellitus Dyslipidemia Triglycerides ≥110 Triglycerides ≥100 Triglycerides ≥150 Triglycerides ≥150 mg/dL Triglycerides ≥150 mg/dL (1.7 (triglycerides) mg/dL mg/dL mg/dL (1.7 mmol/L) or treatment mmol/L) or treatment of of elevated triglycerides elevated triglycerides Dyslipidemia (HDL-C) HDL-C ≤40 mg/dL HDL-C ≤50 mg/dL (1.3 HDL-C <40 mg/dL HDL-C <40 mg/dL (1.03 HDL-C <40 mg/dL (1.03 mmol/L) (1.03 mmol/L; all mmol/L) (1.03 mmol/L) mmol/L) in men and <50 in men and <50 mg/dL (1.3 ages and sexes, mg/dL (<1.29 mmol/L) mmol/L) in women or on drug NCEP) in women or specific treatment of reduced HDL-C treatment of low high- density lipoprotein High BP BP ≥90th percentile BP >90th percentile Systolic BP ≥130 Systolic BP ≥130 mm Hg or Systolic BP ≥130 mm Hg or (age, sex, and mm Hg or diastolic BP ≥85 mm Hg diastolic BP ≥85 mm Hg height specific) diastolic BP or treatment of previously or treatment of previously ≥85 mm Hg diagnosed hypertension diagnosed hypertension or treatment of previously diagnosed hypertension BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; WC, waist circumference.

“ ” defining either the insulin resistance the NCEP first developed the any 3 between them with respect to cut syndrome or MetS among adults: of 5 risk criteria definition. The 5 points of the various component ’ the World22 Health Organization23 risks included in the NCEP ATP III risks (Table 1). The differences in (WHO),​ the NCEP s ATP III,​ the definition are (1) hyperglycemia, these definitions have important American Association of Clinical (2) hypertriglyceridemia, (3) low implications for case identification.

Endocrinologists/American24 College HDL-C, (4) hypertension, and (5) For example, an adult with increased waist circumference. In of Endocrinology,​ the International25 hyperglycemia, hypertriglyceridemia, Diabetes Federation (IDF),​ and the 2005, the AHA/NHLBI modified this and low HDL-C but with a normal American Heart Association (AHA) definition by revising the glucose cut waist circumference would have in conjunction with the National point down and adding allowance MetS according the NCEP but not Heart, Lung, and Blood Institute for drug treatment of dyslipidemia the IDF. In contrast, a person with and impaired fasting glucose. That (NHLBI) of16 the National Institutes “ ” hyperinsulinemia, low HDL-C, of Health. A detailed comparison same year, the IDF introduced its25 and obesity would have MetS of these definitions is beyond the worldwide definition of MetS,​ according to the WHO criteria scope of this report. The definitions lowering the waist circumference cut but not per the NCEP guidelines differ significantly, with most but not points for certain racial and ethnic because hyperinsulinemia is not a all requiring a minimum number of groups and putting greater emphasis risk factor used by the NCEP. These risk factors, some excluding those on abdominal obesity by making differences between definitions lead it a necessary criterion for MetS with a diagnosis of type 2 diabetes to differences in their prognostic3,26​ mellitus, and most differing in the diagnosis. ability and case identification. ‍ For types, required number, and specific Although the AHA/NHLBI and IDF example, in one of the earliest articles cut points for the criterion risk definitions have many similarities, on MetS27 in adolescents, Goodman factors. As noted previously, in 2001, there are important differences et al found a greater than twofold Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017 e3 its definition. In adulthood, MetS

predicts 2,CVD31​ and type 72 diabetes mellitus. ‍ Malik et al found that compared with those who have no MetS risk factors, the hazard ratio for coronary heart disease mortality was 2.87 for those with MetS without diabetes and 5.02 for those with

MetS and diabetes. Depending on 3 the definition used, Laaksonen et al found that the odds ratio (OR) for men with MetS developing diabetes in the 4-year follow-up period was 5 to 8.8. Data from the Princeton Prevalence and Follow-up Studies demonstrated that pediatric MetS predicted adult MetS with an OR of 9.4 and adult type 2 diabetes mellitus with an OR of 11.5; this FIGURE 1 study arbitrarily 32used 2 different Proposed mechanisms for the clustering of MetS traits and the increased risk of type 2 diabetes MetS definitions. However, the mellitus and CVD. CRP, C-reactive protein; FFA, free fatty acids; IL-6, interleukin 6; LDL-C, low-density lipoprotein cholesterol; PAI-1, plasminogen activator inhibitor 1; TNF α, tumor necrosis factor α. utility of the syndrome in adolescents (Reprinted with permission from Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin has also been questioned, given North Am. 2014;43[1]:23.) studies indicating instability of– the

definition when transitioning10,33​ from35 adolescence to adulthood. ‍ ‍‍ Large proportions of children defined difference in the prevalence of WHO- only apply to children 10 years and as having MetS during childhood do defined MetS compared with NCEP- older and that, among those between not meet the diagnostic criteria10,34​ on defined MetS in the Princeton School 10 and 16 years of age, the 90th follow-up 3 to 6 years later. ‍ In District Study. percentile for waist circumference multiple observational longitudinal Defining MetS in Pediatrics or adult cut point (whichever was studies, although population-level lower) should define abdominal prevalence has increased, within- obesity. The IDF stated that for person variation in presence or those 16 years and older, adult Definitions of MetS for children and absence of MetS has been large, with criteria should apply. Two years adolescents have been even more many studies showing 50%‍ or more later, the AHA published its scientific varied than the definitions used of MetS-positive subjects becoming statement on MetS in children and ∼ for adults. The first researchers 8 MetS-negative over time, whether adolescents,​ which emphasized 36 addressing MetS in– a pediatric that be with short-term ( 3 weeks) the need to identify pediatric 35 population focused on or longer-term (9 years) follow-up. 13,14,​ 27​ 29 cardiometabolic risks and noted that adolescents. ‍ ‍ ‍ Even The instability was not related to only some of these were found in the 35 researchers that used the same change in weight status. Thus, criteria used to define MetS. The AHA database (the National Health and MetS is highly unstable throughout did not include a definition of MetS Nutrition Examination Survey III) childhood. A child can meet the for use in pediatric populations and had divergent prevalence estimates, criteria at 1 point in time and not 13 14 indeed made particular note of the ranging from 4.2%‍ to 9.2%‍,​ a meet it at another point in time, and limitations of adapting definitions difference of greater than twofold. it is unclear whether this variation derived for adults to pediatric More than 40 different pediatric represents an improvement or 30 populations. To date, there is no clear 35 definitions of MetS have been used. deterioration in health status. consensus on whether MetS should In 2007, the IDF brought together an be defined in pediatric populations international group of experts and Ethnic or racial differences in rates 9 and, if defined, which definition to developed a consensus definition. 8,9​ of obesity and MetS components also use. ‍ In that report, the IDF recommended exist. Hispanic and black non-Hispanic that pediatric MetS be based on the The controversy over the utility children demonstrate higher rates adult IDF definition but that it should of MetS in pediatrics goes beyond of obesity than white non-Hispanic Downloaded from www.aappublications.org/news by guest on September 26, 2021 e4 FROM THE AMERICAN ACADEMY OF PEDIATRICS 37 children across age categories. Bogalusa Heart Study demonstrated strong. Twin and family studies However, similar to adults, black substantially increased development have revealed substantial familial non-Hispanic youth demonstrate38 and severity of atherosclerotic lesions aggregation of MetS risk factors. Family lower rates of dyslipidemia,​ greater associated with increased clustering41 history of atherosclerotic CVD is a insulin resistance, and higher blood of atherosclerotic CVD risk factors. well-known genetic risk for high lipid pressure than white8 non-Hispanic and Furthermore, the AAP recommends concentrations, high blood pressure,45 Hispanic youth. Hispanic children that pediatricians do not need to use and high glucose concentration. have increased dyslipidemia (elevated cut points based on MetS definitions. Obesity, at the core of MetS, is itself – total cholesterol, low HDL-C, or high The MetS construct identifies multiple highly heritable through shared genetic non HDL-C) compared with black component risk factors that appear and environmental factors. If a parent non-Hispanic39 and white non-Hispanic to cluster together and whose is obese, his or her child is twice as children. Because of the racial and/ pathologic origins arise from insulin likely to be obese, and conversely, or ethnic differences in dyslipidemia, resistance and adiposopathy. Much more than half of children with obesity46 and despite increased prevalence of of the discrepancy in definitions have at least 1 parent with obesity. obesity and greater risk for type 2 derives from differences in these Several MetS risk factors have diabetes mellitus, black non-Hispanic thresholds. Moreover, for many origins during the prenatal and youth have a lower prevalence of risk factors, the risk is a continuum. early postnatal period. The presence MetS than white non-Hispanic or Continuous variables may be more 28 of maternal gestational diabetes; Hispanic youth,​ which can lead to an reliable in predicting young adult low birth weight, especially with underestimation of cardiometabolic risk from early adolescence and 40 42 rapid catch-up growth; infant risk. might help determine future risk. feeding practices (restrictive and A number of researchers have used pressuring); and early adiposity Given the absence of a consensus on factor analysis of MetS components rebound are associated with later the definition of MetS, the unstable to develop a continuous risk score development of obesity and other nature of MetS, and the lack of clarity measure to identify children at higher 8,9​ MetS components. ‍ Throughout about the predictive value of MetS for risk for developing a chronic disease 43,44​ childhood and adolescence, future health in pediatric populations, related to MetS into adulthood. ‍ socioeconomic factors and parental pediatricians are rightly confused Although such work currently is not obesity also affect development of the about MetS. The high prevalence of clinically applicable, with advances in 8,9​ 5 MetS component risk factors. ‍ pediatric obesity and limited resources research and development of clinically to address the obesity problem in applicable risk score guidelines, a Health behavioral factors also are pediatrics reveal the need to identify continuous risk score approach may associated with and can predict the a subset of children with obesity or be created for use in general pediatric presence of MetS risks, particularly who are overweight and at increased practice in the future. At the moment, obesity, in youth. Specific behaviors risk for cardiovascular and metabolic however, risk factor screening and include short duration of sleep, complications beyond the physical identification of youth with MetS risk excessive screen time, specific complications of obesity. Although factor abnormalities allow providers dietary factors, low physical activity,47,48​ obesity is, in general, associated with to target scarce resources to children and tobacco smoke exposure. ‍ increased mechanical stress and at increased cardiometabolic risk, Even after controlling for potential orthopedic complications, particularly those with multiple demographic factors, the number not all children with obesity component abnormalities. Such of hours a child spends each day in manifest metabolic dysregulation screening and associated treatment front of a screen is directly related as a consequence of their obesity. (see below) is an important component to BMI and calories consumed

Identifying children with multiple of preventive pediatric care. per day and inversely related49 to metabolic derangements allows Determinants of Metabolic Risk minutes of physical activity. New targeting of focused interventions Factor Clustering AAP policies discourage screen use toward children at the highest risk for except for video chatting before 18 cardiometabolic disease. Thus, rather to 24 months of age and recommend than focus on defining MetS in youth, There are multiple determinants of that pediatricians help families the American Academy of Pediatrics the 5 risk factors currently used to develop a Family Media Use Plan (AAP) recommends that pediatricians define MetS in adolescents or in adults. specific for each child that ensures focus on the concept of cardiovascular Familial influences include shared entertainment screen time does risk factor clustering and associated genetic and environmental factors, not displace healthy behavioral risk factor screening. This concept which combine to make heritability factors, such as adequate sleep is especially important because the of these individual MetS components and physical activity. (The AAP Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017 e5 Family Media Use plan is available published in 2007, suggest biannual and endothelial dysfunction at www.​healthychildren.50,51​ ​org/​ screening for NAFLD by measuring and is related to hypertension. MediaUsePlan.) Physical activity aspartate aminotransferase and Moreover, studies have revealed is beneficial for weight management, alanine aminotransferase among that treatment of OSA improves and it has also been negatively children with BMI at60 or greater than multiple components of MetS, such associated with MetS and factors that the 85th percentile. as blood65, pressure,66​ lipids, and glucose overlap with MetS, independent of The risk for PCOS is increased in girls control. ‍ As in MetS, the comorbid weight status. Short sleep duration with obesity. PCOS is characterized conditions mentioned here share inversely predicts cardiometabolic by hyperandrogenism (elevated associations with insulin resistance risk in adolescents with obesity, free testosterone), menstrual and obesity, which potentially play a even when controlling for degree irregularities and/or ovulatory role in their pathology as well. of obesity52 and levels of physical dysfunction, and polycystic ovaries. Screening activity. Some studies in adults Obesity and insulin resistance (with and children have found a U-shaped resulting hyperinsulinemia) are relationship between sleep duration associated with PCOS as well as Given the complexity of defining and cardiometabolic risk, with – with increased free testosterone MetS in adolescence, the evolving either too much or too little sleep 53 55 and ovarian and adrenal understanding of MetS, and the lack being problematic. ‍‍ Although hyperandrogenism. The increased of consensus regarding definition, exact mechanisms remain unknown, – luteinizing hormone pulse frequency it is not surprising that there is factors related to inflammation, and increased luteinizing hormone no consensus as to whether or oxidative stress, and antioxidant – follicle-stimulating hormone ratio how MetS should be identified in status are thought to mediate the observed in PCOS (although not pediatric populations, particularly sleep duration cardiometabolic 56 part of diagnostic criteria) result in adolescents. However, there is a health relationship. increased androgen secretion61 from consensus among the American Among the multiple dietary factors theca cells in the ovaries. Diabetes Association and AHA that associated with obesity, lack of Obesity and type 2 diabetes mellitus obesity prevention and treatment in whole grain and fiber intake is have been associated with worse childhood and adolescence should be most strongly correlated with the the first-line approach to alleviating mental health, including increased60,62,​ 63​ 67 development of insulin resistance57 risk for anxiety and depression. ‍ ‍ cardiometabolic risk. Published even after adjusting for BMI. Higher Chronic disease is a well- guidelines recommend that primary consumption of fruits and vegetables, recognized stressor, and obesity care clinicians perform annual obesity which contribute dietary fiber as is associated with social stigma screening for all children by using well as micronutrients, is known to and discrimination. Thus, obesity BMI and refer children with BMI at or reduce risk of atherosclerotic CVD,58 an and diabetes screening guidelines greater than the 95th percentile to a end point of MetS in adulthood. often recommend mental health comprehensive60,68,​ 69​ weight-management Comorbidities screening, as do the current AAP program. ‍ ‍ In practice, it is recommendations for children who sometimes not possible to refer all such children to a comprehensive program. are overweight60 or children with Pediatricians can develop the expertise Comorbidities of MetS, insulin obesity. and resources necessary to manage resistance, and obesity include OSA is a condition characterized by these patients themselves, especially nonalcoholic fatty liver disease complete or partial obstruction of when no comprehensive program (NAFLD), polycystic ovary syndrome the upper airway and is associated exists in their catchment area. (PCOS), obstructive sleep apnea (OSA), with obesity. OSA causes sleep and mental health disorders. NAFLD fragmentation, intermittent hypoxia, In addition to obesity screening with represents a spectrum of damage to and increased negative airway 64 BMI, children should be screened the liver, from steatosis to fibrosis pressure in the thoracic cavity. annually for elevated blood pressure and cirrhosis. NAFLD is defined by Obesity increases the risk for OSA in primary care by using auscultatory – having liver fat >5%‍ liver weight (not because of enlarged soft tissues in methods for69 obtaining blood caused by alcohol consumption) and and around the airway as well as pressure. Nonfasting non HDL-C is strongly 59associated with insulin decreased lung volumes because64 or fasting lipid screening should be resistance. Although there is not a of increased abdominal fat. performed in all children between69 consensus about testing frequency Interestingly, OSA is independently the ages of 9 and 11 years. This among professional organizations, associated with CVD, insulin approach will help to identify children current AAP recommendations, resistance, type 2 diabetes mellitus, with genetic forms of dyslipidemia Downloaded from www.aappublications.org/news by guest on September 26, 2021 e6 FROM THE AMERICAN ACADEMY OF PEDIATRICS and will also identify those with persist into adulthood. Furthermore, stimulus for insulin production. high triglycerides and low HDL-C treatment of obesity and treatment Reducing mitochondrial substrate because of metabolic problems. of MetS components share many by caloric restriction,6 particularly Although insulin resistance is the key common elements, and interventions lipogenic substrates,​ could also to the etiology of MetS, the Insulin that improve 1 condition are likely to be effective. In addition, increased Resistance Consensus group did not ameliorate the other. Meta-analyses dietary fiber intake decreases recommend screening for insulin70 of pediatric lifestyle intervention the glycemic load to the liver. resistance with fasting insulin. studies have revealed that dietary Increased physical activity improves Screening for glucose intolerance and modification and increased mitochondrial efficiency, which6 type 2 diabetes mellitus is important physical activity decrease weight is preventive against MetS,​ and because hyperglycemia is one of the and also improve cardiometabolic improves insulin sensitivity. As MetS component risks. Risk factors activity levels increase, inflammatory risk factors such as68, dyslipidemia72​ for type 2 diabetes mellitus include and hypertension. Decreased cytokines and markers of oxidative overweight or obesity, belonging to a obesity also results in decreases in stress decrease, insulin sensitivity high-risk racial and/or ethnic group, increases, endothelial function insulin resistance73 and inflammatory family history of type 2 diabetes markers. Good evidence suggests improves,81 and HDL-C concentrations mellitus, physical signs of insulin that moderate- to high-intensity increase. Time spent in moderate to resistance (acanthosis nigricans), weight-loss programs combined vigorous physical activity is inversely PCOS, dyslipidemia, or hypertension. with behavioral counseling, negative associated with a MetS continuous Methods of screening have included energy balance diets, and increased risk score, and those who spent at the oral glucose tolerance, hemoglobin least 88 minutes per day in moderate physical activity, can successfully A1c, fasting glucose, and random 68 to vigorous physical activity were 67,​71 address obesity. Combining diet 82 glucose tests. The authors of the least likely to have MetS. and exercise is more effective at expert committee obesity guidelines achieving decreases in BMI than Pharmacotherapeutic options to from 2007 recommended that children 83 either intervention in isolation. No treat obesity in children are limited. 10 years or older (or pubertal) researchers have demonstrated Currently, only orlistat has an with a BMI at or greater than evidence for recommending a specific FDA indication for weight loss in the 85th percentile and 2 additional dietary plan because appropriate adolescents as young as 12 years risk factors be screened with 60 restriction of calories is the main of age. Orlistat, an intestinal lipase a fasting glucose test every 2 years. issue. Low-glycemic-load diets and inhibitor, results in a mean 3%‍ weight Treatment low-carbohydrate diets may be loss (on the84, 85​basis of starting weight) at more effective than low-fat diets in 6 months. ‍ Adverse effects include steatorrhea and flatulence, making it reducing weight and improving69 CVD Treatment of MetS involves both risk, at least in the short-term. difficult to use in practice. Insurance85 behavioral and pharmacotherapeutic Specific lifestyle targets that have coverage for orlistat is variable. interventions aimed at reducing demonstrated efficacy in reducing Bariatric86 surgery in adolescents is obesity, glucose abnormalities, BMI include substitution of sugar- effective and reserved for the most severely affected. hypertension, and dyslipidemia. sweetened beverages– with water, Once identified, pediatricians should milk, or artificially74 77 sweetened– Treatment of MetS risk factor treat these component risk factors beverages ‍ ‍ and reducing77 79 components is well described in by using current best practices television or screen time. ‍ It is several evidence-based guidelines. (summarized or referenced later in important to note that achieving The authors of the NHLBI Expert Panel this report) to reduce future risk for a normal BMI is not necessary to guidelines, published in 2011, provide cardiometabolic disease. decrease cardiometabolic risk. evidence-based guidance for dietary Studies have revealed that weight and pharmacotherapeutic treatment Obesity treatment is grounded in loss and improvement in BMI by 5%‍80 of dyslipidemia and hypertension lifestyle modification, and early to 10%‍ can have metabolic benefits. in children and adolescents. The treatment of obesity in childhood type of dyslipidemia associated and adolescence is recommended as The mechanisms that explain with MetS usually is treated with the first-line approach to reducing 60,67,​ 69​ the association between lifestyle lifestyle intervention only,69 not with cardiometabolic risk. ‍ ‍ Obesity modification and effects on MetS pharmacologic agents. Treatment is a more stable trait than MetS, components are not fully understood. of insulin resistance involves lifestyle more likely to be present at multiple Dietary interventions that lower modification only. Anecdotally, some points in time, and more likely to intake of simple sugars may reduce providers are using metformin to Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017 e7 Staff Debra Burrowes, MHA treat children and adolescents who 3. by following current have insulin resistance with normal recommendations to screen Section on Endocrinology Executive glucose concentrations. Although for and treat obesity, glucose Committee, 2015–2016 some studies have revealed beneficial abnormalities, hypertension, Irene N. Sills, MD, FAAP, Chairperson effects of metformin on BMI and and dyslipidemia, pediatricians Samuel J. Casella, MD, MSc, FAAP homeostatic model assessment of are addressing the major MetS- Linda A. DeMeglio, MD, MPH, FAAP insulin resistance score in adolescents associated cardiometabolic risks Jose L. Gonzalez, MD, JD, MSEd, FAAP Paul B. Kaplowitz, MD, FAAP, Immediate Past with insulin resistance, these trials in pediatric populations; Chairperson were only 6 months in length and 87 4. identification of children with Jane L. Lynch, MD, FAAP, Chairperson Elect Kupper A. Wintergerst, MD, FAAP involved small numbers of subjects. multiple component risks enables Thus, metformin is not currently pediatricians to apply their most Staff recommended70 for treatment of insulin intensive intervention efforts to Laura Laskosz, MPH resistance. No consensus exists in the children and adolescents in the pediatric diabetes community as to greatest need of risk reduction; Section on Obesity Executive treatment of prediabetes in children, and Committee, 2015–2016 other than lifestyle management. Christopher F. Bolling, MD, FAAP, Chairperson Children found to have prediabetes 5. increasing awareness of comorbid conditions such as Sarah C. Armstrong, MD, FAAP or type 2 diabetes mellitus on Natalie Digate Muth, MD, MPH, RD, FAAP screening can be referred to a pediatric NAFLD, mental health disorders, John C. Rausch, MD, MPH, FAAP PCOS, and OSA enables Victoria Weeks Rogers, MD, FAAP endocrinologist88 for management and/ or monitoring. It is also critical to pediatricians to address and refer Robert P. Schwartz, MD, FAAP to specialists, as needed. screen for and address any comorbid Liaison conditions, such as PCOS or OSA, which Continued efforts to prevent and CDR Alyson Goodman, MD, MPH, FAAP – Centers often share the causal link of insulin treat obesity and its associated for Disease Control and Prevention resistance with MetS component risk metabolic abnormalities among factors. children and adolescents and Staff vigilant attention to the early Mala Thapar, MPH Summary diagnosis of diabetes provide the ’ pediatrician with the most evidence- based methods for addressing Abbreviations MetS evolved from Reaven s cardiometabolic risk factor clustering concept of syndrome X, a tool used (MetS) in adolescence. to understand the many effects Authors AAP: American Academy of of insulin resistance on human Sheela N. Magge, MD, MSCE, FAAP Pediatrics physiology. In adults, a diagnosis Elizabeth Goodman, MD, MBA, FAAP AHA: American Heart of MetS is associated with an Sarah C. Armstrong, MD, FAAP Association increased risk for CVD and diabetes. Committee on Nutrition, 2015–2016 ATP III: Adult Treatment Panel In pediatrics, there remain many Stephen Daniels, MD, PhD, FAAP, Chairperson III unanswered questions regarding Mark Corkins, MD, FAAP CVD: cardiovascular disease the definition of and utility of the Sarah de Ferranti, MD, FAAP HDL-C: high-density lipoprotein diagnosis of MetS. Therefore,​ Neville H. Golden, MD, FAAP cholesterol Jae H. Kim, MD, PhD, FAAP IDF: International Diabetes 1. although pediatricians can use Sheela N. Magge, MD, MSCE, FAAP MetS as an organizing frame, Sarah Jane Schwarzenberg, MD, FAAP Federation the focus for clinical screening MetS: metabolic syndrome and treatment should be on Liaisons NAFLD: nonalcoholic fatty liver cardiometabolic risk factors, many Carrie L. Assar, PharmD, MS – Food and Drug disease of which cluster together and are Administration NCEP: National Cholesterol associated with obesity; Jeff Critch, MD – Canadian Pediatric Society Education Program Van Hubbard, MD, PhD, FAAP – National Institutes NHLBI: National Heart, Lung, 2. pediatricians should not focus the of Health and Blood Institute specific levels of cardiometabolic Kelley Scanlon, PhD – Centers for Disease Control OR: odds ratio risk factors from the multitude of and Prevention Valery Soto, MS, RD, LD – US Department of OSA: obstructive sleep apnea MetS definitions because the risk Agriculture PCOS: polycystic ovary syndrome lies on a continuum and in the WHO: World Health Organization context of the whole child; Downloaded from www.aappublications.org/news by guest on September 26, 2021 e8 FROM THE AMERICAN ACADEMY OF PEDIATRICS DOI: https://​doi.​org/​10.​1542/​peds.​2017-​1603

Address correspondence to Sheela N. Magge, MD, MSCE, FAAP. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2017 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

References 1. Reaven GM. Banting lecture 1988. Role 8. Steinber ger J, Daniels SR, Eckel RH, in American adolescents: findings from of insulin resistance in human disease. et al; American Heart Association the third National Health and Nutrition Diabetes. 1988;37(12):1595–1607 Atherosclerosis, Hypertension, and Examination Survey. Circulation. Obesity in the Young Committee 2004;110(16):2494 2497 2. Meigs JB. Invited commentary: insulin – of the Council on Cardiovascular resistance syndrome? Syndrome 15. Alber ti KG, Zimmet P, Shaw J. Metabolic Disease in the Young; Council on X? Multiple metabolic syndrome? syndrome a new world-wide definition. Cardiovascular Nursing; and Council – A syndrome at all? Factor analysis A Consensus Statement from the on Nutrition, Physical Activity, and reveals patterns in the fabric of International Diabetes Federation. Metabolism. Progress and challenges correlated metabolic risk factors. Am J Diabet Med. 2006;23(5):469 480 in metabolic syndrome in children and – Epidemiol. 2000;152(10):908 911 – adolescents: a scientific statement 16. Grundy SM, Cleeman JI, Daniels SR, 3. Laaksonen DE, Lakka HM, Niskanen from the American Heart Association et al. Diagnosis and management of LK, Kaplan GA, Salonen JT, Lakka TA. Atherosclerosis, Hypertension, and the metabolic syndrome: an American Metabolic syndrome and development Obesity in the Young Committee of the Heart Association/National Heart, of diabetes mellitus: application Council on Cardiovascular Disease in Lung, and Blood Institute scientific and validation of recently suggested the Young; Council on Cardiovascular statement: executive summary. definitions of the metabolic syndrome Nursing; and Council on Nutrition, Circulation. 2005;112(17):2735–2752 in a prospective cohort study. Am J Physical Activity, and Metabolism. 17. Rask-Madsen C, Kahn CR. Tissue- Epidemiol. 2002;156(11):1070 1077 Circulation. 2009;119(4):628 647 – – specific insulin signaling, metabolic 4. Yip J, Facchini FS, Reaven 9. Zimmet P, Alberti KG, Kaufman F, et al; syndrome, and cardiovascular disease. GM. Resistance to insulin- IDF Consensus Group. The metabolic Arterioscler Thromb Vasc Biol. mediated glucose disposal as syndrome in children and adolescents 2012;32(9):2052–2059 a predictor of cardiovascular - an IDF consensus report. Pediatr 18. Ginsber g HN, Zhang YL, Hernandez-Ono disease. J Clin Endocrinol Metab. Diabetes. 2007;8(5):299 306 – A. Regulation of plasma triglycerides in 1998;83(8):2773 2776 – 10. Goodman E, Daniels SR, Meigs JB, insulin resistance and diabetes. Arch 5. Grundy SM, Brewer HB Jr, Cleeman Dolan LM. Instability in the diagnosis Med Res. 2005;36(3):232–240 JI, Smith SC Jr, Lenfant C; American of metabolic syndrome in adolescents. 19. Guilherme A, Virbasius JV, Puri V, Czech Heart Association; National Heart, Circulation. 2007;115(17):2316 2322 – MP. Adipocyte dysfunctions linking Lung, and Blood Institute. Definition 11. Goodman E. Metabolic syndrome and obesity to insulin resistance and of metabolic syndrome: Report of the mismeasure of risk. J Adolesc type 2 diabetes. Nat Rev Mol Cell Biol. the National Heart, Lung, and Blood Health. 2008;42(6):538 540 2008;9(5):367 377 Institute/American Heart Association – – conference on scientific issues 12. Goodman E. Pediatric metabolic 20. Yudkin JS. Insulin resistance and related to definition. Circulation. syndrome: smoke and mirrors or true the metabolic syndrome–or the 2004;109(3):433–438 magic? J Pediatr. 2006;148(2):149–151 pitfalls of epidemiology. Diabetologia. 2007;50(8):1576 1586 6. Bremer AA, Mietus-Snyder M, Lustig 13. Cook S, Weitzman M, Auinger P, Nguyen – RH. Toward a unifying hypothesis M, Dietz WH. Prevalence of a metabolic 21. Hotamisligil GS. Endoplasmic of metabolic syndrome. Pediatrics. syndrome phenotype in adolescents: reticulum stress and the inflammatory 2012;129(3):557–570 findings from the third National Health basis of metabolic disease. Cell. 7. Malik S, Wong ND, Franklin SS, et al. and Nutrition Examination Survey, 2010;140(6):900–917 Impact of the metabolic syndrome on 1988-1994. Arch Pediatr Adolesc Med. 22. Alber ti KG, Zimmet PZ. Definition, mortality from coronary heart disease, 2003;157(8):821–827 diagnosis and classification of diabetes cardiovascular disease, and all causes 14. de Ferranti SD, Gauvreau K, Ludwig mellitus and its complications. Part in United States adults. Circulation. DS, Neufeld EJ, Newburger JW, Rifai N. 1: diagnosis and classification of 2004;110(10):1245–1250 Prevalence of the metabolic syndrome diabetes mellitus provisional report

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017 e9 of a WHO consultation. Diabet Med. 32. Morrison JA, Friedman LA, Wang P, 42. Kelly AS, Steinberger J, Jacobs 1998;15(7):539–553 Glueck CJ. Metabolic syndrome in DR, Hong CP, Moran A, Sinaiko AR. childhood predicts adult metabolic Predicting cardiovascular risk in 23. Exper t Panel on Detection, Evaluation, syndrome and type 2 diabetes young adulthood from the metabolic and Treatment of High Blood mellitus 25 to 30 years later. J Pediatr. syndrome, its component risk factors, Cholesterol in Adults. Executive 2008;152(2):201 206 and a cluster score in childhood. Int J summary of the third report of – Pediatr Obes. 2011;6(2 2): the National Cholesterol Education 33. Ventura EE, Lane CJ, Weigensberg MJ, – e283 e289 Program (NCEP) Expert Panel on Toledo-Corral CM, Davis JN, Goran MI. – detection, evaluation, and treatment Persistence of the metabolic syndrome 43. Gurka MJ, Ice CL, Sun SS, Deboer MD. of high blood cholesterol in adults over 3 annual visits in overweight A confirmatory factor analysis of the (Adult Treatment Panel III). JAMA. Hispanic children: association with metabolic syndrome in adolescents: an 2001;285(19):2486–2497 progressive risk for type 2 diabetes. examination of sex and racial/ethnic J Pediatr. 2009;155(4):535 541 differences. Cardiovasc Diabetol. 24. Einhorn D, Reaven GM, Cobin RH, et al. – 2012;11:128 American College of Endocrinology 34. Gustafson J, Easter B, Keil M, et al. position statement on the insulin Instability of the diagnosis of metabolic 44. Goodman E, Dolan LM, Morrison JA, resistance syndrome. Endocr Pract. syndrome in children. Obesity. Daniels SR. Factor analysis of 2003;9(3):237–252 2007;15(suppl):A172 clustered cardiovascular risks in adolescence: obesity is the 25. Alber ti KG, Zimmet P, Shaw J; IDF 35. Stanley TL, Chen ML, Goodman predominant correlate of risk Epidemiology Task Force Consensus E. The typology of metabolic among youth. Circulation. Group. The metabolic syndrome a syndrome in the transition to – 2005;111(15):1970–1977 new worldwide definition. Lancet. adulthood. J Clin Endocrinol Metab. 2005;366(9491):1059–1062 2014;99(3):1044–1052 45. Bao W, Srinivasan SR, Valdez R, Greenlund KJ, Wattigney WA, 26. Ford ES, Giles WH. A comparison of the 36. Gustafson JK, Yanoff LB, Easter Berenson GS. Longitudinal changes in prevalence of the metabolic syndrome BD, et al. The stability of metabolic cardiovascular risk from childhood using two proposed definitions. syndrome in children and to young adulthood in offspring of Diabetes Care. 2003;26(3):575–581 adolescents. J Clin Endocrinol Metab. parents with coronary artery disease: 2009;94(12):4828 4834 27. Goodman E, Daniels SR, Morrison – the Bogalusa Heart Study. JAMA. JA, Huang B, Dolan LM. Contrasting 37. Ogden CL, Carroll MD, Kit BK, Flegal 1997;278(21):1749–1754 prevalence of and demographic KM. Prevalence of childhood and adult 46. Whitaker RC, Wright JA, Pepe MS, disparities in the World Health obesity in the United States, 2011-2012. Seidel KD, Dietz WH. Predicting obesity Organization and National Cholesterol JAMA. 2014;311(8):806–814 in young adulthood from childhood Education Program Adult Treatment 38. Kit BK, Carroll MD, Lacher DA, Sorlie and parental obesity. N Engl J Med. Panel III definitions of metabolic PD, DeJesus JM, Ogden C. Trends 1997;337(13):869–873 syndrome among adolescents. in serum lipids among US youths 47. Fadzlina AA, Harun F, Nurul Haniza J Pediatr. 2004;145(4):445–451 aged 6 to 19 years, 1988-2010. JAMA. MY, et al. Metabolic syndrome among 28. Duncan GE, Li SM, Zhou X-H. 2012;308(6):591–600 13 year old adolescents: prevalence Prevalence and trends of a metabolic 39. Kit BK, Kuklina E, Carroll MD, Ostchega and risk factors. BMC Public Health. syndrome phenotype among U.S. Y, Freedman DS, Ogden CL. Prevalence 2014;14(suppl 3):S7 adolescents, 1999-2000. Diabetes Care. of and trends in dyslipidemia and 48. Farber HJ, Groner J, Walley S, Nelson K; 2004;27(10):2438 2443 – blood pressure among US children and Section on Tobacco Control. Protecting 29. Cruz ML, Weigensberg MJ, Huang adolescents, 1999-2012. JAMA Pediatr. children from tobacco, nicotine, TT, Ball G, Shaibi GQ, Goran MI. The 2015;169(3):272–279 and tobacco smoke. Pediatrics. metabolic syndrome in overweight 40. Yu SS, Ramsey NL, Castillo DC, Ricks 2015;136(5). Available at: www.​ Hispanic youth and the role of insulin M, Sumner AE. Triglyceride-based pediatrics.​org/​cgi/​content/​full/​136/​5/​ sensitivity. J Clin Endocrinol Metab. screening tests fail to recognize e1439 2004;89(1):108 113 – cardiometabolic disease in African 49. Crespo CJ, Smit E, Troiano RP, 30. Ford ES, Li C. Defining the metabolic immigrant and African-American Bartlett SJ, Macera CA, Andersen RE. syndrome in children and adolescents: men. Metab Syndr Relat Disord. Television watching, energy intake, will the real definition please stand 2013;11(1):15–20 and obesity in US children: results up? J Pediatr. 2008;152(2):160–164 41. Berenson GS, Srinivasan SR, Bao W, from the third National Health and Nutrition Examination Survey, 1988- 31. Meigs JB, D’Agostino RB Sr, Wilson Newman WP III, Tracy RE, Wattigney PW, Cupples LA, Nathan DM, Singer WA. Association between multiple 1994. Arch Pediatr Adolesc Med. DE. Risk variable clustering in the cardiovascular risk factors and 2001;155(3):360–365 insulin resistance syndrome. The atherosclerosis in children and young 50. Council on Communications and Media. Framingham Offspring Study. Diabetes. adults. The Bogalusa Heart Study. N Media and young minds. Pediatrics. 1997;46(10):1594–1600 Engl J Med. 1998;338(23):1650–1656 2016;138(5):e20162591

Downloaded from www.aappublications.org/news by guest on September 26, 2021 e10 FROM THE AMERICAN ACADEMY OF PEDIATRICS 51. Council on Communications and overweight and obesity: summary of Primary Care Interventions for Media. Media use in school-aged report. Pediatrics. 2007;120(suppl Weight Management in Children and children and adolescents. Pediatrics. 4):S164–S192 Adolescents: An Updated, Targeted 2016;138(5):e20162592 61. Anderson AD, Solorzano CM, McCartney Systematic Review for the USPSTF [Internet]. Rockville, MD: Agency for 52. Iglayreger HB, Peterson MD, CR. Childhood obesity and its impact on Healthcare Research and Quality (US); Liu D, et al. Sleep duration the development of adolescent PCOS. 2010 predicts cardiometabolic risk Semin Reprod Med. 2014;32(3):202–213 in obese adolescents. J Pediatr. 62. Silverstein J, Cheng P, Ruedy KJ, et al; 69. Exper t Panel on Integrated Guidelines 2014;164(5):1085–1090.e1 Pediatric Diabetes Consortium. for Cardiovascular Health and Risk Reduction in Children and Adolescents; 53. Koren D, Levitt Katz LE, Brar PC, Depressive symptoms in youth with National Heart, Lung, and Blood Gallagher PR, Berkowitz RI, Brooks type 1 or type 2 diabetes: results of Institute. Expert panel on integrated LJ. Sleep architecture and glucose the pediatric diabetes consortium guidelines for cardiovascular and insulin homeostasis in obese screening assessment of depression health and risk reduction in adolescents. Diabetes Care. in diabetes study. Diabetes Care. children and adolescents: summary 2011;34(11):2442 2447 2015;38(12):2341–2343 – report. Pediatrics. 2011;128(suppl 54. Yu Y, Lu BS, Wang B, et al. Short 63. Nemiary D, Shim R, Mattox G, Holden 5):S213–S256 sleep duration and adiposity K. The relationship between obesity and depression among adolescents. 70. Levy-Marchal C, Arslanian S, Cutfield in Chinese adolescents. Sleep. W, et al; ESPE-LWPES-ISPAD-APPES- Psychiatr Ann. 2012;42(8):305–308 2007;30(12):1688–1697 APEG-SLEP-JSPE; Insulin Resistance 55. Ohkuma T, Fujii H, Iwase M, et al. 64. Drager LF, Togeiro SM, Polotsky VY, in Children Consensus Conference Impact of sleep duration on obesity Lorenzi-Filho G. Obstructive sleep Group. Insulin resistance in children: and the glycemic level in patients apnea: a cardiometabolic risk in consensus, perspective, and future with type 2 diabetes: the Fukuoka obesity and the metabolic syndrome. directions. J Clin Endocrinol Metab. Diabetes Registry. Diabetes Care. J Am Coll Cardiol. 2013;62(7):569–576 2010;95(12):5189–5198 2013;36(3):611–617 65. Dorkova Z, Petrasova D, Molcanyiova A, 71. American Diabetes Association. Popovnakova M, Tkacova R. Effects of 56. Kanagasabai T, Ardern CI. Contribution Standards of medical care in continuous positive airway pressure of inflammation, oxidative stress, diabetes-2016: summary of revisions. on cardiovascular risk profile in and antioxidants to the relationship Diabetes Care. 2016;39(suppl 1):S4–S5 patients with severe obstructive sleep between sleep duration and apnea and metabolic syndrome. Chest. 72. Ho M, Garnett SP, Baur L, et al. cardiometabolic health. Sleep. Effectiveness of lifestyle interventions 2008;134(4):686–692 2015;38(12):1905–1912 in child obesity: systematic review with 66. Sharma SK, Agrawal S, Damodaran D, 57. Steffen LM, Jacobs DR Jr, Murtaugh meta-analysis. Pediatrics. 2012;130(6). et al. CPAP for the metabolic syndrome MA, et al. Whole grain intake is Available at: www.​pediatrics.​org/​cgi/​ in patients with obstructive sleep associated with lower body mass content/​full/​130/​6/​e1647 apnea [retracted in N Engl J Med. and greater insulin sensitivity 2013;369(18):1770]. N Engl J Med. 73. Meyer AA, Kundt G, Lenschow U, Schuff- among adolescents. Am J Epidemiol. Werner P, Kienast W. Improvement 2011;365(24):2277–2286 2003;158(3):243–250 of early vascular changes and 67. Steinber ger J, Daniels SR; American 58. Steffen LM, Jacobs DR Jr, Stevens cardiovascular risk factors in Heart Association Atherosclerosis, J, Shahar E, Carithers T, Folsom obese children after a six-month Hypertension, and Obesity in the AR. Associations of whole-grain, exercise program. J Am Coll Cardiol. Young Committee (Council on refined-grain, and fruit and vegetable 2006;48(9):1865–1870 Cardiovascular Disease in the Young); consumption with risks of all-cause American Heart Association Diabetes 74. Albala C, Ebbeling CB, Cifuentes M, mortality and incident coronary artery Committee (Council on Nutrition, Lera L, Bustos N, Ludwig DS. Effects of disease and ischemic stroke: the Physical Activity, and Metabolism). replacing the habitual consumption of Atherosclerosis Risk in Communities Obesity, insulin resistance, diabetes, sugar-sweetened beverages with milk (ARIC) Study. Am J Clin Nutr. and cardiovascular risk in children: an in Chilean children. Am J Clin Nutr. 2003;78(3):383 390 – American Heart Association scientific 2008;88(3):605–611 59. Ahmed MH, Barakat S, Almobarak statement from the Atherosclerosis, 75. Ebbeling CB, Feldman HA, Chomitz AO. Nonalcoholic fatty liver disease Hypertension, and Obesity in the Young VR, et al. A randomized trial of and cardiovascular disease: has the Committee (Council on Cardiovascular sugar-sweetened beverages and time come for cardiologists to be Disease in the Young) and the Diabetes adolescent body weight. N Engl J Med. hepatologists? J Obes. 2012;2012:1–9 Committee (Council on Nutrition, 2012;367(15):1407–1416 60. Barlow SE; Expert Committee. Expert Physical Activity, and Metabolism). 76. Ebbeling CB, Feldman HA, Osganian SK, committee recommendations Circulation. 2003;107(10):1448–1453 Chomitz VR, Ellenbogen SJ, Ludwig DS. regarding the prevention, assessment, 68. Whitlock EP, O’Conner EA, Williams Effects of decreasing sugar-sweetened and treatment of child and adolescent SB, Beil TL, Lutz KW. Effectiveness beverage consumption on body

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 2, August 2017 e11 weight in adolescents: a randomized, Research Group. Reduction in the co-morbid conditions. J Pediatr controlled pilot study. Pediatrics. incidence of type 2 diabetes with Endocrinol Metab. 2004;17(3): 2006;117(3):673–680 lifestyle intervention or metformin. N 307–319 77. French SA, Sherwood NE, JaKa MM, Engl J Med. 2002;346(6):393–403 85. McDuffie JR, Calis KA, Uwaifo GI, et al. Haapala JL, Ebbeling CB, Ludwig 81. Schmitz KH, Jacobs DR Jr, Hong CP, Three-month tolerability of orlistat DS. Physical changes in the home Steinberger J, Moran A, Sinaiko in adolescents with obesity-related environment to reduce television AR. Association of physical activity comorbid conditions. Obes Res. viewing and sugar-sweetened with insulin sensitivity in children. 2002;10(7):642–650 beverage consumption among 5- to Int J Obes Relat Metab Disord. 86. Inge TH, Courcoulas AP, Jenkins TM, 12-year-old children: a randomized 2002;26(10):1310–1316 et al; Teen-LABS Consortium. Weight pilot study. Pediatr Obes. 2016; 82. Stabelini Neto A, de Campos W, loss and health status 3 years after 11(5):e12–e15 Dos Santos GC, Mazzardo Junior O. bariatric surgery in adolescents. 78. Best JR, Theim KR, Gredysa DM, et Metabolic syndrome risk score and N Engl J Med. 2016;374(2): al. Behavioral economic predictors time expended in moderate to vigorous 113–123 of overweight children’s weight physical activity in adolescents. BMC 87. Park MH, Kinra S, Ward KJ, White loss. J Consult Clin Psychol. Pediatr. 2014;14:42 B, Viner RM. Metformin for obesity 2012;80(6):1086–1096 83. Yanovski SZ, Yanovski JA. Long- in children and adolescents: a 79. Epstein LH, Roemmich JN, Robinson JL, term drug treatment for obesity: a systematic review. Diabetes Care. et al. A randomized trial of the effects systematic and clinical review. JAMA. 2009;32(9):1743–1745 of reducing television viewing and 2014;311(1):74–86 88. Copeland KC, Silverstein J, Moore KR, computer use on body mass index in 84. McDuffie JR, Calis KA, Uwaifo GI, et al. et al; American Academy of Pediatrics. young children. Arch Pediatr Adolesc Efficacy of orlistat as an adjunct to Management of newly diagnosed Med. 2008;162(3):239–245 behavioral treatment in overweight type 2 diabetes mellitus (T2DM) in 80. Knowler WC, Barrett-Connor E, Fowler African American and Caucasian children and adolescents. Pediatrics. SE, et al; Diabetes Prevention Program adolescents with obesity-related 2013;131(2):364–382

Downloaded from www.aappublications.org/news by guest on September 26, 2021 e12 FROM THE AMERICAN ACADEMY OF PEDIATRICS The Metabolic Syndrome in Children and Adolescents: Shifting the Focus to Cardiometabolic Risk Factor Clustering Sheela N. Magge, Elizabeth Goodman, Sarah C. Armstrong, COMMITTEE ON NUTRITION, SECTION ON ENDOCRINOLOGY and SECTION ON OBESITY Pediatrics 2017;140; DOI: 10.1542/peds.2017-1603 originally published online July 24, 2017;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/140/2/e20171603 References This article cites 87 articles, 30 of which you can access for free at: http://pediatrics.aappublications.org/content/140/2/e20171603#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Current Policy http://www.aappublications.org/cgi/collection/current_policy Committee on Nutrition http://www.aappublications.org/cgi/collection/committee_on_nutritio n Section on Endocrinology http://www.aappublications.org/cgi/collection/section_on_endocrinol ogy Section on Obesity http://www.aappublications.org/cgi/collection/section-on-obesity Nutrition http://www.aappublications.org/cgi/collection/nutrition_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 26, 2021 The Metabolic Syndrome in Children and Adolescents: Shifting the Focus to Cardiometabolic Risk Factor Clustering Sheela N. Magge, Elizabeth Goodman, Sarah C. Armstrong, COMMITTEE ON NUTRITION, SECTION ON ENDOCRINOLOGY and SECTION ON OBESITY Pediatrics 2017;140; DOI: 10.1542/peds.2017-1603 originally published online July 24, 2017;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/140/2/e20171603

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2017 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on September 26, 2021