These include inflammatory cytokines, thrombotic and inflammatory markers, and vasoactive substances that contribute directly or indirectly to changes in vasculature and CVD.
The recognition of medications that induce weight gain may be an efficient measure to identify children at risk of obesity. Medication-induced weight gain is often overlooked and may be associated with an increased risk of complications, such as diabetes, asthma, hypertension, and depression. Although not every patient will gain weight while receiving treatment with drugs known to promote weight gain, many will. Health care providers should monitor weight as part of routine assessment. They should be aware of the impact of even a small increase in weight and make appropriate adjustments to the medication regimen or lifestyle. Drugs that have been associated with weight gain and that are often used in children with underlying conditions are listed inTable 3.
In the United States, the most recent estimates of obesity prevalence are based on data from the 19992000 National Health and Nutrition Examination Survey (NHANES IV).
, Farooqi IS, ORahilly S, Cole TJ, Fewtrell M, Lucas A: Early nutrition and leptin concentrations in later life.:999,
, Saad R, Gungor N, Janosky J, Arslanian SA: Obesity, regional t distribution, and syndrome X in obese black versus white adolescents: race differential in diabetogenic and atherogenic risk ctors.:2540,
, Christensen M, Krichevsky S, West B, Rose SR, Velasquez-Mieyer P, Danish R, Broome DC, Lustig RH: Type 2 diabetes mellitus epidemic in African-American children (Abstract).:,
NHANES IV demonstrated that 20.6% of 2- to 5-year-old children in the United States were overweight. In older children, this prevalence was even higher, with 30.3% of 6- to 11-year-old children and 30.4% of adolescents (1219 years of age) being overweight. The prevalence of obesity among children aged 023 months, 25 years, 611 years, and adolescents was 11.4, 10.4, 15.3, and 15.5%, respectively.
, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S: Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.:810,
, Erkelens DW, Terpstra P, Reitsma WD, Doorenbos H: Glucose tolerance and insulin release, a mathematical approach. II. Approximation of the peripheral insulin resistance after oral glucose loading.:-249,
, Ksinantova L, Koska J: Effect of body composition on indices of insulin sensitivity and beta-cell function in healthy men.:77,
Of special consideration are children with pre-existing diseases, who often require the use of medications that may stobesity linked to diabetes in childrenimulate weight gain.
, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.:1470,
How and when to intervene to prevent obesity in childhood is a challenging question. The rapid increase in the prevalence of childhood overweight and its potential effect on morbidity and mortality in childhood and adulthood underscores the importance of identifying critical periods for the prevention of overweight in vulnerable populations and of developing an understanding of ctors that cause excess weight gain. A critical period for overweight or obesity is defined as a time when the risk of onset, complications, or persistence of overweight or obesity is increased.
Obese adolescents (1517 years of age) have 17.5 times greater odds of becoming obese adults compared to normal-weight peers, whereas obese 1- to 2-year-olds have a 1.3 times greater odds of becoming obese adults compared to normal-weight toddlers.
Parental obesity is also an important predictor of childhood obesity. Prepregnancy maternal weight and BMI and maternal weight gain during pregnancy have been independently associated with increased risk of childhood obesity and associated conditions.
, Barouch WW, Ershow AG: Report of the National Heart, Lung, and Blood InstituteNational Institute of Diabetes and Digestive and Kidney Diseases Working Group on the pathophysiology of obesity-associated cardiovascular disease.:2928,
The age of adiposity rebound, the point of the BMI nadir before body tness begins to increase (between 5 and 6 years of age) is also an important predictor for adult obesity.
In BriefCritical periods for the development of childhood obesity have been established. Health care providers should recognize these periods for initiation of interventions to prevent obesity because treatment options once obesity occurs are limited. Greater body weight predisposes children to many of the medical complications of obesity found in adults, including hypertension, dyslipidemia, impaired glucose metabolism, and hyperinsulinemia. Race, genetic predisposition, sedentary lifestyle, duration of overweight, and underlying conditions are major determinants of risk for type 2 diabetes and cardiovascular disease (CVD). However, not all adolescents with these characteristics share a similar risk for developing these conditions. The appropriate risk stratification for adolescents could guide clinicians in recognizing overweight youth who are at higher risk of developing pre-diabetes, diabetes, or CVD and lead to a prompt intervention.
Accurate comparison of resting blood pressure to normative values based on age, , and height resulted in identification of hypertension in 50% of youth who were referred to our clinic as healthy children for weight management. Emerging risk ctors for CVD may provide helpful information beyond that provided by the lipid profile in overweight minority youth.
obesity linked to diabetes in children Identifying Children at Risk for Obesity, Type 2 Diabetes, and,In 1998, the World Health Organization (WHO) designated obesity as a global epidemic affecting adults and children. In general, obesity is defined as the degree of somatic overweight that affords detrimental health consequences. This definition does not contemplate a specific cut-off point, but it allows health care providers to consider individual predisposition when assessing at-risk children, including underlying conditions, mily history, medications, and lifestyle. Within the scientific community, the discovery of leptin and the elucidation of disorders affecting various neuroendocrine pathways and the genetic linkages of obesity have promulgated the notion that obesity is a disease.
, 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 adolescents.:2374,
, Bini V, Cabiati G, Papi F, Arzano S, Celi F, Sanasi M: Serum levels of type I procollagen C-terminal propeptide, insulin-like growth ctor-I (IGF-I), and IGF binding protein-3 in obese children and adolescents: relationship to gender, pubertal development, growth, insulin, and nutritional status.:871,
Despite having a higher incidence of CVD, African Americans may not exhibit the same magnitude or frequency of traditional lipid abnormalities as their white counterparts.
, Obarzanek E, Barton BA, Kimm SY, Similo SL, Morrison JA: Sexual maturation and racial differences in blood pressure in girls: the National Heart, Lung, and Blood Institute Growth and Health Study.:213,
However, this imbalance in the energy equation does not explain differences in t distribution, individual susceptibility to develop obesity-associated comorbidities, or the dissimilar weight loss response to lifestyle and pharmacological interventions. Compared to that in adults, the energy balance in children is more affected by the intrauterine environment, metabolic abnormalities, racial and genetic predisposition, underlying conditions, medications, and other ctors. The interactions of these ctors with social and environmental forces clearly denote differences between children and adults.
Based on the current set of evidence, we speculate that in genetically susceptible populations, the interaction of racial, sociocultural, and biological ctors, triggered or exacerbated by concomitant obesity, ultimately leads to early development of type 2 diabetes and increased risk for CVD in youth. In this review, we hope to provide useful information to assist health care providers in identifying those individuals more vulnerable to becoming obese and developing associated comorbidities.
Elevated levels of FFAs alter the matrix of endothelial cell basement membranes, them more permeable to macromolecules. Diets high in saturated and trans tty acids promote hypercholesterolemia. Macrophages and arterial smooth muscle cells more readily take up LDL cholesterol, especially small dense LDL particles, contributing to the development of atherosclerotic lesions. An LDL particle linked to an apo(a) polypeptide chain, lipoprotein(a), may inhibit endogenous fibrinolysis and be a marker for thromboembolic disease, particularly in youth.
We have found that adolescents at even moderate levels of overweight have already experienced a pronounced reduction in insulin sensitivity.
, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA: Indices of insulin action, disposal, and secretion derived from sting samples and clamps in normal glucose-tolerant black and white children.:2087,
The progression of childhood obesity into adulthood is associated with early development of complications, including type 2 diabetes and CVD. This suggests that the pathogenic process involved in the development of such conditions starts during childhood.
, Harrell JS, Bangdiwala SI, Bradley CB, Deng S, Levine A: A school-based intervention can reduce body t and blood pressure in young adolescents.:132,
, Liu K, Yan LL, Pirzada A, Manheim L, Manning W, Garside DB, Wang R, Dyer AR, Greenland P, Stamler J: Relation of body mass index in young adulthood and middle age to Medicare expenditures in older age.:2749,
, Velasquez-Mieyer PA, Markee J, Weakly C, Christensen M, Burghen G.A.: Impact of overweight on cardiovascular risk ctors of African-American children.:,
A relationship between small-for-gestational-age innts and the development of obesity, cardiovascular complications, and type 2 diabetes has been demonstrated, particularly in minority populations. Conversely, large innts, most commonly a result of gestational diabetes mellitus, also exhibit increased risk for the development of obesity, cardiovascular complications, and type 2 diabetes.
Children with early adiposity rebound have a fivefold greater chance of becoming obese as adults, compared to those with late adiposity rebound. At the age of adiposity rebound, children who are already overweight have a six-fold greater risk for adult obesity compared to lean children. Therefore, the earlier the onset of childhood obesity, the greater the risk of adult obesity.
There is not definitive agreement about which screening tests best reflect the negative impact of increased adiposity on glucose metabolism in adolescents. Screening recommendations vor sting blood glucose (FBG) as the ideal screening method in subjects at risk for IGT or type 2 diabetes because of its low cost and greater convenience. However, we agree with a growing set of evidence suggesting that a single FBG may not reflect the early impact of increasing adiposity on glucose homeostasis nor discriminate between youth with and without IGT/type 2 diabetes until significant deterioration in glucose metabolism has occurred.
, Cowan PA, Christensen M, Lunar L, Markwell S, Burghen GA: Can OGTT-derived indices uncover an overweight threshold for deterioration in adolescent glucose metabolism?(Suppl. 2):,
, Saad R, Janosky J, Arslanian S: Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents.:55,
may further exacerbate the impact of obesity on glucose and lipid metabolism, fostering type 2 diabetes and increasing the risk of early CVD.
In vulnerable individuals, transient changes associated with puberty, including increase in t mass, insulin resistance, leptin, growth hormone, and IGF-I,
Obesity has overtaken AIDS and malnutrition as the top health problem in the world.
Population-based data suggest that the epidemic of pediatric obesity is being followed by an increase in type 2 diabetes, particularly in adolescents of minority groups.
, Cowan PA, Cuervo R, Markee J, Weakley C, Rajanna V, Christensen M, Burghen GA: Does obesity matter in children with type 2 diabetes? (Abstract)(Suppl. 2):,
In youth, central t distribution, whether measured by waist circumference or waist-to-hip ratio, is related to adverse lipid and lipoprotein levels
We have found that both BMI and RBMI are similarly associated with indexes of glucose metabolism and insulin dynamics and cardiovascular risk ctors in our population. RBMI transforms BMI into a continuous variable relative to the ideal reference value (50th percentile on age- and -specific BMI charts) that reflects the severity of overweight, allowing a comparison across age and groups based on severity of overweight and cilitating longitudinal follow-up. Our experience supports the notion that estimating the severity of overweight by RBMI could aid clinicians assessing the magnitude and progression of overweight at different time-points of the growing period in an objective and practical way.
There is solid information showing that type 2 diabetes and risk ctors for CVD have increased in children, particularly in obese adolescents.
screening is not routinely performed in obese youth. Recommended screening for cardiovascular risk ctors in obese youth includes measurement of blood pressure, sting insulin and glucose, and traditional lipoprotein analysis; however, these measures may underestimate cardiovascular risk, particularly in adolescent minorities. Fasting levels of insulin and glucose do not reflect the hyperinsulinemia that occurs during adolescence or the racial differences reported during stimulated glucose tolerance testing.
) young adults have a reduced life expectancy of 520 years. Childhood obesity often persists into adulthood and has been independently associated with subsequent morbidity and mortality in adulthood. However, the sequelae of obesity are not limited to adulthood, as evidenced by the increased incidence of concomitant comorbidities seen in overweight youth (Table 1). It has been suggested that because of the health impact of obesity, this generation may be the first to live a shorter average lifespan than the preceding generation.
BMI is the accepted measure of obesity in children and adolescents. In childhood, comparison of BMI to normal curves for age and allows for categorization of BMI above the 85th percentile as overweight and above the 95th percentile as obese.
, Bowman BA, Otvos JD, Srinivasan SR, Berenson GS: Differences in the relation of obesity to serum triacylglycerol and VLDL subclass concentrations between black and white children: the Bogalusa Heart Study.:833,
The team at the Lifestyle Clinic at LeBonheur Childrens Medical Center in Memphis, Tenn., has validated the use of the relative BMI (RBMI) as a clinical estimation of the percentage of overweight above the ideal BMI percentile. RBMI is an objective way to assess and compare changes to any intervention in our overweight population. RBMI is calculated using the following equation: BMI BMI at 50th percentile for age and 100.
The research data presented in this article were supported by the Childrens Foundation Research Center of Memphis at Le Bonheur Childrens Medical Center and Le Bonheur Health Systems. The authorswould like to thank the staff of the Lifestyle Clinic at Le Bonheur Childrens Medical Center and the Health Evaluation and Lifestyle Promotion (HELP) Center for technical assistance and their assistance in the care of our patients.
Decreased insulin sensitivity (insulin resistance) has been shown to precede the development of type 2 diabetes and CVD. Several mechanisms link excess of adiposity with insulin resistance, including insulin signaling abnormalities, adypokines, sedentary behavior, nonesterified tty acids, and ectopic t infiltration.
Pedro Velasquez-Mieyer, MD, is a culty member in the epidemiology program of the College of Graduate Health Sciences and an assistant professor in the College of Nursing and in the Pediatrics Department, Division of Endocrinology and Metabolism, of the College of Medicine at the University of Tennessee Health Science Center (UTHSC) in Memphis. Sylvia Perez-Faustinelli, MD, is a research associate in the Pediatrics Department, Division of Endocrinology and Metabolism, of the College of Medicine at UTHSC. Patricia A. Cowan RN, PhD, HFI, is an assistant professor in the College of Nursing at UTHSC.
Age- and race-adjusted cardiovascular disease (CVD)-related, type 2 diabetesrelated, and total charges were significantly higher for overweight and obese adults. Total charges for severely obese men and women were $6,192 more (84% higher) and $5,618 more (88% higher), respectively, than for nonoverweight subjects. If the trend in obesity-associated type 2 diabetes and cardiovascular risk ctors continues in children, national expenditures for health care are likely to escalate.
Glycemic Control in Pharmacist-Managed Insulin Titration Versus Standard Care in an Indigent Population
, Meghelli-Bouchenak M, Loukidi B, Prost J, Belleville J: Impaired serum lipids and lipoproteins in fetal macrosomia related to maternal obesity.:24,
These findings suggest that the current screening recommendations may underestimate risk for CVD and diabetes in severely overweight youth, particularly adolescent minorities. We recommend assessment of glucose tolerance by the OGTT and determination of insulin sensitivity using OGTT-derived indexes.
Conversely, indexes reflecting insulin sensitivity clearly support the notion that deterioration of insulin sensitivity with increasing overweight could be the most important pathogenic ctor leading to IGT among adolescents.
The BMI chart is a valuable predictive device and should be used with all children. The higher the BMI during childhood, the more likely adult obesity will manifest. In general, children with a BMI the 95th percentile have a high risk for adult obesity. Children and adolescents with BMI the 95th percentile have a 6298% chance of being obese at 35 years of age.
Greater body weight predisposes children to many of the medical complications of obesity found in adults, in particular components of the metabolic syndrome: hypertension, dyslipidemia, and impaired glucose metabolism. As these children age, the obesity epidemic will lead to epidemics of diabetes, hypertension, and CVD. However, not all overweight adolescents have the same risk of developing these complications. Appropriate risk stratification could guide clinicians to recognize overweight youth who are at higher risk of developing type 2 diabetes or CVD and lead to prompt intervention. Stratification of adolescents based on1) severity of overweight (RBMI),2) estimates of -cell activity and insulin resistance (OGTT-derived indexes), and3) cardiovascular risk profile may be useful for the longitudinal follow-up of overweight youth. Health care providers of overweight children need to pursue efficient screening procedures earlier in the progression of overweight in order to prevent adolescents from developing these diseases.
, Galuska DA, Gillespie C, Will JC, Giles WH, Dietz WH: C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 19881994.:492,
Although studies link childhood obesity to cardiovascular risk ctors that predict CVD,
, Malina RM, Bouchard C: Physical activity, physical fitness, and coronary heart disease risk ctors in youth: the Quebec Family Study.:562,
, Nastasi K, Hilton C, Bao W, Srinivasan SR, Berenson GS: Black-white contrasts in insulin levels during pubertal development.:317,
, Srinivasan SR, Harsha DW, Webber LS, Berenson GS: Relation of body t patterning to lipid and lipoprotein concentrations in children and adolescents: the Bogalusa Heart Study.:939,
Early overnutrition has been correlated with elevated leptin concentrations, a marker of adiposity in later life.
Obesity markedly reduces life expectancy, especially among younger individuals. Severely obese (BMI > 45 kg/m
, Cowan PA, Christensen M, Markwell S, Umpierrez GE, Velasquez P: Insulin sensitivity deterioration may be the most important ctor in the pathogenesis of type 2 diabetes (T2DM) among adolescents.(Suppl. 2):,
, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from sting plasma glucose and insulin concentrations in man.:419,
Food deprivation in early pregnancy also has been suggested as an independent risk ctor for obesity in adults.
For instance, the prevalence of obesity among African-American (23.6%) and Hispanic (23.4%) adolescents is twice that among white adolescents (12.7%), and the rate of increase in the prevalence of obesity among African-American and Hispanic adolescents almost doubled between the periods 19881994 and 19992000, from 13.4 to 23.6% in African Americans and from 13.8 to 23.4% in Hispanics.
, Rumberger JM, Stuart CA, Ruhoff MS: Stimulation of lipolysis by tumor necrosis ctor-alpha in 3T3-L1 adipocytes is glucose dependent: implications for long-term regulation of lipolysis.:81,
Simple methods of assessing insulin sensitivity and secretion are important in the evaluation and follow-up of youth with obesity and risk ctors for type 2 diabetes. The OGTT is a clinically and widely used procedure originally developed to classify carbohydrate tolerance. The effectiveness and reliability of the OGTT to establish the diagnosis of IGT/type 2 diabetes have been demonstrated in children. Plasma glucose and insulin response during the OGTT reflect the ability of pancreatic -cells to secrete insulin and the sensitivity of tissues to insulin. Therefore, many investigators have studied and validated surrogate indexes of -cell function and insulin resistance in children and adults based on values obtained during the OGTT
, Silverman BL, Rizzo TA, Metzger BE: Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers.:592,
Defects of insulin secretion, insulin action, hepatic glucose production, or combinations of these mechanisms characterize childhood type 2 diabetes. These defects are likely triggered or exacerbated by concurrent obesity, sedentary lifestyle, unhealthy eating habits, and hormonal changes (puberty) in genetically susceptible populations that ultimately could lead to -cell ilure and the appearance of glucose intolerance and diabetes.
, Flegal KM, Carroll MD, Johnson CL: Prevalence and trends in overweight among US children and adolescents, 1999-2000.:1732,
Both overweight severity and central (abdominal) adipose distribution are associated with cardiovascular risk ctors and development of glucose intolerance in adults, with abdominal adiposity, particularly visceral t mass, considered to be more deleterious than peripheral t mass.
, Lai D, Turner J, Poffenbarger T, Portman RJ: Overweight, ethnicity, and the prevalence of hypertension in school-aged children.:482,
A relationship has been found between BMI in young adulthood and middle age to subsequent health care expenditures at ages 65 years.
Clinical criteria for defining the metabolic syndrome in adults have been developed by the WHO and the National Cholesterol Education Program Adult Treatment Panel III. In adults, specific cut-off points have been delineated for these clinical criteria of waist circumference, systolic and diastolic blood pressure, serum triglyerides and HDL cholesterol, and sting glucose. Several studies have examined the frequency of the metabolic syndrome in youth based on components of the adult criteria. The lack of standardized criteria and cut-points for defining the metabolic syndrome in youth makes comparisons across studies difficult. Despite the use of diverse criteria and cutpoints, results from these studies substantiate that the metabolic syndrome is already highly prevalent among obese children and adolescents.
, Ball , Cruz ML: Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents.:1427,
, Trost SG, Brown WJ, Batch JA: Indexes of insulin resistance and secretion in obese children and adolescents: a validation study.:319,
Postnatal ctors, including innt overnutrition, play an extremely important role in the future development of obesity. A pattern of rapid weight gain during the first 4 months of life also has been associated with an increased risk of overweight status at age 7 years, independent of birth weight and weight attained at age 1 year.
Prevention of childhood obesity is critical because obesity is associated with the development of unvorable health outcomes during childhood and adulthood. It has been overemphasized that the major etiopathogenic ctors contributing to obesity result from an imbalance in the energy equation produced by either increased energy intake or decreased energy expenditure or both. This notion has led health providers to develop a simplistic perception that societal and nutritional changes (i.e., the toxic environment) are the chief parameters that foster the current epidemic of obesity, type 2 diabetes, and CVD in children.
This risk increases as the child becomes older. Change in BMI during and after adolescence is the most important predictive variable for adult obesity.
, Knowler WC, Pettitt DJ, Nelson RG, Charles MA, Bennett PH: A two-step model for development of non-insulin-dependent diabetes.:235,
Adipose tissue is a metabolically active endocrine organ producing a large number of hormones, peptides, andobesity linked to diabetes in children Identifying Children at Risk for Obesity, Type 2 Diabetes, and small molecules that affect metabolism and cardiovascular regulation.
, Koletzko B, Sauerwald T, von Mutius E, Barnert D, Grunert V, von Voss H: Breast feeding and obesity: cross sectional study.:150,
Chronic, subclinical inflammation has been identified as one mechanism explaining the increased risk of obesity-associated CVD and diabetes. This awareness has lead to an increased interest in emerging markers of cardiovascular risk, such as CRP, fibrinogen, and PAI-1. A number of studies have examined relationships between obesity and these emerging cardiovascular risk ctors in children. In youth, severity of obesity assessed by t mass was associated with increased levels of fibrinogen
(Table 4). The OGTT-derived indexes provide clinically useful information that allows the estimation of insulin secretion capacity and insulin sensitivity, both of which are essential for defining the treatment approach. Indexes reflecting -cell secretion capacity clearly help clinicians to demonstrate that -cell workload increases with overweight. However, these -cell indexes are not good predictors for type 2 diabetes because overweight adolescents with glucose intolerance show insulin secretion capacity at a level that is at least equivalent to those with normal glucose tolerance.
in adolescents. However, the lack of age- and -specific normative values for waist circumference or waist-to-hip ratios among children makes it difficult to identify which youth are at greater risk for developing these obesity-associated conditions.
Deterioration of insulin sensitivity has been shown to be one of the best predictors of IGT and type 2 diabetes in adolescents, and severity of overweight is the major cause of such deterioration (R
, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P: Increased incidence of non-insulin-dependent diabetes mellitus among adolescents.:615,
Health providers taking care of obese children require a practical and objective way to assess the severity and progression of overweight in children who are still growing. The current consensus is that BMI is a valid and feasible indirect measure of body tness. The BMI cutoff points are linked to adult cutoff points for overweight and obesity, which are good indicators of risks for adverse health outcomes. They correlate with markers of obesity-related complications, including blood pressure, lipid profile, and insulin resistance, as well as with long-term mortality.
In severely obese African-American youth, we found that established cardiovascular risk ctors of elevated total and LDL cholesterol occurred, respectively, in 48 and 33% of the youth. Hypertriglyceridemia and low HDL cholesterol, components of the metabolic syndrome, occurred less frequently (13 and 24%, respectively), whereas hypertension (values > the 95th percentile based on norms for age, , and height) was present in 50% of the youth.
, Kunselman AR, Dodson WC, Dunaif A: Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women.:169,
, Gutin B, Owens S, Litaker M, Tracy RP, Allison J: Fat distribution and hemostatic measures in obese children.:1140,
Lean children 5 years of age have a 13-fold risk of adult obesity if both parents are obese, suggesting that genetic influences predominate in childhood weight gain. Obesity, type 2 diabetes, and CVD often run in milies, particularly in minorities with lower socioeconomic backgrounds.
It has been well demonstrated that cardiovascular risk ctors frequently occur in obese youth and that these risk ctors tend to cluster. Obesity and insulin resistance are hypothesized to be the underlying mechanism for this clustering of risk ctors, known as the metabolic syndrome. Central adiposity, atherogenic dyslipidemia, hypertension, insulin resistance, glucose intolerance, and a prothrombotic, proinflammatory state characterize the metabolic syndrome.
Differences in both volume and composition of commercial formula compared to breast milk have also been proposed as etiological ctors of childhood obesity.
, Eriksson JG, Forsen T, Osmond C: Fetal origins of adult disease: strength of effects and biological basis.:1239,
BMI is to use, consistent for children and adolescents, and very useful in clinical practice and in epidemiological studies. However, it suffers from a number of limitations. BMI cutoff points do not permit comparison of severity of overweight across age and groups, nor do they provide a comprehensive way to longitudinally follow overweight in youth. In children and adolescents, BMI cutoff points are constantly changing, and they are expected to progressively increase until reaching adult BMI values (18 years of age).
Presently, the lack of clinical indicators to identify youth at higher risk of developing impaired glucose tolerance (IGT) or type 2 diabetes precludes clinicians from early intervention to stop its progression. Commonly, referrals for glucose tolerance testing in severely obese children are triggered by the development of symptoms rather than geared toward identification of children at risk who could benefit from early intervention. Using a standardized screening protocol for high-risk groups, we have found a fourfold higher prevalence of abnormalities in glucose metabolism in youth with BMIs between the 85th and 95th percentiles.
, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a , accurate method for assessing insulin sensitivity in humans.:2410,
In agreement with these investigations, we have reported that 66% of severely overweight adolescents with IGT during the oral glucose tolerance test (OGTT) and have an FBG value < 100 mg/dl at the time of their initial evaluation. Therefore, the opportunity for earlier intervention in these adolescents will be missed.
Chronic, subclinical inflammation may be one pathophysiological mechanism explaining the increased risk of atherosclerotic CVD and diabetes associated with obesity. Adipose tissue expresses inflammatory cytokines and stimulates the release of inflammatory and thrombotic markers, such as C-reactive protein (CRP) and fibrinogen, which contribute to the development of tty streaks and more advanced atherosclerotic lesions. Leptin may increase platelet aggregation and arterial thrombosis. It has been suggested that flux in free tty acids (FFAs) promotes thrombosis through alterations in protein C, plasminogen activator inhibitor-1 (PAI-1), and enhanced platelet aggregation.
Several cross-sectional studies have examined established cardiovascular risk ctors in overweight and lean youth. Compared to lean peers, overweight youth are more likely to have lipid abnormalities and elevated blood pressure.
Physical inactivity is recognized as a risk ctor for obesity, CVD, and type 2 diabetes. In a predominantly white group of 610 9- to 18-year-olds, higher levels of cardiorespiratory fitness and habitual physical activity were associated with more vorable levels of triglycerides, LDL and HDL cholesterol, sting glucose, and blood pressure.
We have reported that overweight adolescents with a composite insulin sensitivity index (CISI) (Table 4) < 2.0 were 10 times more likely to have IGT than overweight adolescents with a higher CISI.
, Preeyasombat C, Velasquez-Mieyer P: Treatment of childhood obesity. In. Eugster E, Pescovitz O, Eds. Charlottesville, Va., Lippincott, Williams, and Wilkins,, p.714
In contrast, a study of 82 African-American sixth graders found no significant relationships between blood pressure and physical activity or adiposity.
The American Diabetes Association estimates that between 8 and 45% of children newly diagnosed with diabetes have type 2 diabetes. In the greater Memphis, Tenn., area, the authors have reported a fivefold increase in childhood type 2 diabetes between 1990 and 2001, with type 2 diabetes accounting for 43% of the newly diagnosed cases in 2000 and overweight African-American adolescents accounting for roughly 86% of the new cases.
, Chan W, Cummings SS, Simons-Morton BG, Day RS, Sangi-Haghpeykar H, Pivarnik JS, Mueller WH, Detry MA, Wei, II, Johnson-Masotti AP, Hsu HA: Healthy growth: project description and baseline findings.:577,
have reported modest associations between blood pressure and cardiorespiratory fitness (r= -0.33) and BMI (r= 0.33) in a multiethnic cohort of 11- to 14-year-olds. These inconsistencies may be partially attributed to the varying methods of measuring physical activity and the use of absolute values for blood pressure and lipid levels rather than age-adjusted values. Our work suggests that both cardiovascular fitness and severity of overweight contribute to cardiovascular risk in African-American youth, with the percentage of overweight and cardiorespiratory fitness accounting for 34% of the variance in the cardiovascular risk profile.
As a consequence of this epidemic, annual hospital costs for obesity and obesity-associated conditions in youth (617 years of age) increased from $35 million during the period from 1979 to 1981 to $127 million during the period from 1997 to 1999.
Macrosomic innts of obese mothers exhibit enhanced insulin resistance, as suggested by higher serum lipids, lipoprotein apolipoprotein (apo) B100, and apo (A-1).
This epidemic equally affects both es, and its prevalence has increased compared to data from the previous NHANES reports in all age ranges and racial groups. However, minorities are over-represented in this epidemic.
In order to provide appropriate care, clinicians and other health care providers ce several challenges, including lack of well-validated assessment algorithms, very limited long-term treatment experience, and few approved tools for the treatment of childhood obesity and associated complications. Efforts to identify the negative impact of obesity at its incipient stages may justify early and more aggressive treatment intervention to prevent the progression and development of complications.
Children with at least one overweight parent at the age of adiposity rebound have a four- to fivefold greater chance of becoming obese adults.
We agree with other investigators that the accuracy of surrogate estimates of -cell function may be diminished once IGT is present.
Some evidence suggests that the rate of weight gain during the first few months of life and related determinants, such as type of innt feeding, may influence weight status later in childhood as well as the later development of adult CVD. The prevalence of obesity in children who were never breastfed was 4.5%, compared to 2.8% in breastfed children, and a clear time-response effect was identified for the duration of breastfeeding on the decline in prevalence of obesity.
, Wu W, Chumlea WC, Roche AF: Predicting overweight and obesity in adulthood from body mass index values in childhood and adolescence.:658,
Factors associated with the antenatal environment and the fetus appear to be important components in the development of childhood obesity, type 2 diabetes, and CVD. Effects of the intrauterine environment on cell numbers, satiety centers in the brain, and endocrine function represent mechanisms that may logically account for the apparent prenatal channeling of either restricted or exuberant growth.
, Khan LK, Dietz WH, Srinivasan SR, Berenson GS: Relationship of childhood obesity to coronary heart disease risk ctors in adulthood: the Bogalusa Heart Study.:718,
It has been shown that FBG is a poor predictor of diabetes in obese adolescents and subjects with polycystic ovarian syndrome.
, Pepe MS, Wright JA, Seidel KD, Dietz WH: Early adiposity rebound and the risk of adult obesity (Abstract).:,
, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Hayflick L, Butler RN, Allison DB, Ludwig DS: A potential decline in life expectancy in the United States in the 21st century.:1145,
, Howard BV, Robbins DC: Dyslipidemia of obesity. InObesity: Endotext.Caro JS, Ed., 2003. Available online from
suggests that antenatal stress or placental insufficiency programs metabolic alterations in -cell function and insulin sensitivity that persist into adult life and promote the development of the metabolic syndrome. Third-trimester amniotic fluid insulin levels have been related to childhood obesity, insulin resistance, and systolic hypertension.
, Zemel BS, Kumanyika S, Stallings VA: Innt weight gain and childhood overweight status in a multicenter, cohort study.:199,
Risk ctors associated with the antenatal environment, the early postnatal years, adiposity rebound (56 years of age), and puberty have been identified within different critical periods for the development of obesity (Table 2). Health providers should recognize these critical periods in the development of children during which interventions may successfully prevent obesity.
Greater intra-abdominal t mass has also been shown to correlate with higher basal insulin, higher triglyceride levels, higher blood pressure,
We found that 43% of obese youth had elevated CPR, and 38% had elevated fibrinogen, despite having normal LDL cholesterol levels.
