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Effect of a short-term diet and exercise intervention on metabolic syndrome in overweight children

      Abstract

      Overweight and the metabolic syndrome are increasing radically in children. The present study was designed to examine the effects of lifestyle modification in 16 children who were placed on a high-fiber, low-fat diet in a 2-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn. Insulin (27.2 ± 3.5 vs 18.3 ± 1.7 μU/mL, P < .01), homeostasis model assessment for insulin resistance (5.79 ± 0.81 vs 4.13 ± 0.38, P < .05), and body weight (92.0 ± 7.0 vs 88.0 ± 6.8 kg, P < .01) were reduced significantly. Total cholesterol (165 ± 7.8 vs 127 ± 7.4 mg/dL, P < .01), low-density lipoprotein (94.1 ± 8.2 vs 68.5 ± 6.7 mg/dL, P < .01), triglycerides (146 ± 16.2 vs 88.1 ± 8.1 mg/dL, P < .01), and total cholesterol–high-density lipoprotein (4.16 ± 0.30 vs 3.34 ± 0.30, P < .01) and low-density lipoprotein–high-density lipoprotein ratios (2.41 ± 0.3 vs 1.86 ± 0.2, P < .01) were reduced, with no change in high-density lipoprotein observed (42.3 ± 2.4 vs 40.8 ± 3.0 mg/dL). Systolic blood pressure (130 ± 3.1 vs 117 ± 1.8 mm Hg, P < .001) and diastolic blood pressure (74.3 ± 3.0 vs 67.2 ± 2.3 mm Hg, P = .01) also decreased. Most notably, before the intervention, 7 of the 16 subjects were classified with metabolic syndrome. After the 2-week intervention, despite remaining overweight, reversal of metabolic syndrome was noted in all 7 subjects. All of these changes occurred despite only modest improvements in the percentage of body fat (37.5% ± 1.1% vs 36.4% ± 1.2%, P < .01) and body mass index (33.2 ± 1.9 vs 31.8 ± 1.9 kg/m2, P < .01). These results indicate that a short-term rigorous diet and exercise regimen can reverse metabolic syndrome, even in youth without documented atherosclerosis.

      1. Introduction

      Obesity is a significant public health issue in the United States [
      • Caterson I.D.
      • Gill T.P
      Obesity: epidemiology and possible prevention.
      ,
      • Reilly J.J.
      • Dorosty A.R.
      • Emmett P.M
      Prevalence of overweight and obesity in British children: cohort study.
      ], and children and adolescents have not eluded this emerging epidemic. In 2000, more than 15% of children and adolescents in the United States aged 6 to 19 years were classified as overweight (body mass index [BMI] >95th percentile), more than triple the percentage recorded 30 years earlier [
      • National Center for Health Statistics
      Health, United States, 2002, with chartbook on trends in the health of Americans.
      ]. In addition, the Centers for Disease Control and Prevention (CDC) reported that 62% of children 9 to 13 years of age do not participate in any organized physical activity during nonschool hours [
      Physical activity levels among children aged 9-13 years—United States, 2002.
      ]. Consequently, today's overweight children and adolescents are potentially setting the stage for heightened risk of cardiovascular disease, type 2 diabetes mellitus, cancer, osteoarthritis, and premature all-cause mortality later in life [
      • Khaodhiar L.
      • McCowen K.C.
      • Blackburn G.L
      Obesity and its comorbid conditions.
      ].
      Obesity is highly correlated with a constellation of disorders including dyslipidemia, insulin resistance, and hypertension—hallmarks of the metabolic syndrome and risk factors for cardiovascular disease. Diagnosis of this syndrome is indicated when 3 or more of the following risk factors coexist: central obesity, elevated blood pressure, elevated fasting glucose or insulin resistance/hyperinsulinemia, elevated triglycerides (TG), and reduced high-density lipoprotein (HDL). According to the Third National Health and Nutrition Examination Survey, between 1988 and 1994, it was estimated that the metabolic syndrome was present in more than 6% of overweight adolescents and more than 25% of obese adolescents [
      • Cook S.
      • Weitzman M.
      • Auinger P.
      • et al.
      Prevalence of a metabolic syndrome phenotype in adolescents: findings from the Third National Health and Nutrition Examination Survey, 1988-1994.
      ]. Accumulating evidence indicates that the prevalence of these metabolic abnormalities is increasing among the youth of America and other industrialized countries [
      • Vincent S.D.
      • Pangrazi R.P.
      • Raustorp A.
      • et al.
      Activity levels and body mass index of children in the United States, Sweden, and Australia.
      ,
      • James P.T.
      • Rigby N.
      • Leach R.
      The obesity epidemic, metabolic syndrome and future prevention strategies.
      ,
      • Deckelbaum R.J.
      • Williams C.L.
      Childhood obesity: the health issue.
      ]. The ramifications are significant, given that overweight children tend to remain overweight or become obese in adulthood [
      • Magarey A.M.
      • Daniels L.A.
      • Boulton T.J.
      • et al.
      Predicting obesity in early adulthood from childhood and parental obesity.
      ], and predicts that the percentage of adults at risk for the metabolic syndrome and cardiovascular disease will continue to climb if current overweight trends continue [
      • Berenson G.S
      Childhood risk factors predict adult risk associated with subclinical cardiovascular disease: The Bogalusa Heart Study.
      ].
      Although it is clear that overweight and obesity prevalence is increasing in children and adolescents in westernized societies, there are few studies examining combined physical activity and diet interventions in this subset of the population. The goal of this study was to investigate the effects of short-term daily physical activity and a low-fat, high-fiber diet on the metabolic syndrome and related coronary artery disease (CAD) risk factors in overweight youth.

      2. Methods

      2.1 Subjects

      Children and adolescents (n = 16) between the ages of 10 and 17 years participated in a 2-week residential lifestyle modification program at the Pritikin Longevity Center in Aventura, FL. In the summer of 2002, the Pritikin Longevity Center offered a special program where parents were permitted to bring their children for a 1- or 2-week session. Eighteen children were enrolled in the 2-week session. Two families left early for unknown reasons, and thus pre and post data were obtained from 16 children, 10 males and 6 females. None of the subjects were using drugs or therapies for obesity, and none had prior histories of disease or injury that would prevent daily exercise. Consent to participate in a research program was obtained from the parents, all subjects agreed to provide data for the study, and the project was approved by the University of California, Los Angeles (UCLA) Human Subjects Protection Committee.

      2.2 Diet and exercise intervention

      Participants in the program received a complete physical examination and underwent a 14-day diet and exercise intervention. Prepared meals, which were well tolerated by the subjects, contained 12% to 15% of energy from fat (polyunsaturated-saturated fatty acid ratio, 2.4:1), 15% to 20% of energy from protein, and 65% to 70% of energy from primarily unrefined carbohydrate, high in dietary fiber (>40 g/d). Carbohydrates were primarily in the form of high-fiber whole grains (≥5 servings per day), vegetables (≥4 servings per day), and fruits (≥3 servings per day). Protein was primarily derived from plant sources, with nonfat dairy (up to 2 servings per day) and fish and fowl served (in 3 1/2 oz portions) 4 d/wk and in soups or casseroles (2 d/wk). The diet contained less than 100 mg of cholesterol, and caffeinated beverages were not allowed during the program. Sodium intake was limited to less than 1600 mg/d. All foods except animal-derived protein sources were served ad libitum. Subjects participated in 1 to 2 cooking classes daily, where small snacks were sampled. In addition, participants in the study attended twice-daily lectures discussing nutrition, exercise, and general wellness.
      The exercise intervention consisted of 2 to 2.5 hours of supervised activity per day, including tennis, beach games, and gym-based exercises intended to encourage physical activity in the subjects. This deviates from the standard Pritikin program recommendations for adults of 45 to 60 minutes of exercise at the training heart rate (70%-85% of maximal heart rate as determined by a graded exercise stress test) because of the young ages of the subjects and the desire to have the subjects enjoy physical activity. The goal was to increase activity and energy expenditure, and, as such, heart rate was not measured during exercise.
      Fasting blood samples were drawn on days 1 and 12 of the intervention. The blood was separated by centrifugation and sent on dry ice to the UCLA laboratory and stored at −80°C until analysis. Height, body weight, waist circumference, body fat percentage, resting heart rate, and blood pressure measures were also assessed on these days.

      2.3 Determination of serum lipids, glucose, insulin, homeostatic model assessment for insulin resistance, and quantitative insulin-sensitivity check index

      Total cholesterol, triglycerides (TG), HDL, and glucose levels were measured at a national commercial laboratory (Quest Diagnostics, Miami, FL) using standardized techniques as previously described [
      • Wegge J.K.
      • Roberts C.K.
      • Ngo T.H.
      • et al.
      Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease.
      ]. Low-density lipoprotein (LDL) was calculated as described by the Friedewald formula [
      • Friedewald W.T.
      • Levy R.I.
      • Fredrickson D.S.
      Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
      ]. Insulin was quantified in duplicate using enzyme-linked immunosorbent assay (Diagnostic Systems Laboratories, Webster, TX). The degree of insulin resistance was determined with the use of the homeostatic model assessment for insulin resistance (HOMA-IR). Scores typically range from 0 to 15, with higher scores indicating greater insulin resistance, and are calculated as the product of the fasting plasma insulin level (μU/mL) and the fasting plasma glucose level (mmol/L), divided by 22.5. The estimate obtained with HOMA-IR correlates well with measures of insulin resistance obtained from overweight and non-overweight children and adolescents with the use of the hyperinsulinemic-euglycemic clamp technique [
      • Sinha R.
      • Fisch G.
      • Teague B.
      • et al.
      Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.
      ]. Insulin sensitivity was determined by the quantitative insulin-sensitivity check index (QUICKI), as defined by 1/{log[fasting insulin (μU/mL)] + log[fasting glucose (mg/dL)]}. The QUICKI has also been shown to correlate well with the hyperinsulinemic-euglycemic clamp in both obese and nonobese individuals [
      • Katz A.
      • Nambi S.S.
      • Mather K.
      • et al.
      Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.
      ].

      2.4 Determination of body composition and BMI classification

      Body composition was measured by dual-energy x-ray absorptiometry (DEXA, Hologic QDR4500 Fan Beam X-ray Densitometer, Hologic, Waltham, MA). The mean weight was measured using a scale from Pennsylvania Medical Scales (model no. 7500, Pennsylvania Scale Co, Leola, PA). The scale was not recalibrated during the 2-week study. Weights were taken in the morning before breakfast, with subjects in a T-shirt and shorts. Subjects were asked to remove their shoes. Height was measured using a Seca stadiometer (Seca Corp, Hanover, MD), attached to the wall. Body mass index was calculated as the weight in kilograms divided by the square of height in meters. Equations provided by the CDC (http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/datafiles.htm) were used to generate Z scores of BMI values that were then applied to estimate sex-specific BMI-for-age percentiles for each subject and obesity risk classification for each subject. Body mass index percentile categories included <5th (underweight), ≥5th to 84th (normal weight), ≥85th to 94th (at risk for overweight), and ≥95th (overweight).

      2.5 Blood pressure classification

      Algorithms provided by the CDC were used to generate sex- and age-specific Z scores for height, which were combined with recently published standards for sex- and age-specific norms concerning systolic, and diastolic blood pressure to calculate systolic, and diastolic percentiles for each subject. Blood pressure classification was based on the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescent report [
      National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.
      ] that incorporates the CDC age, height, and sex classification scheme as follows: “desirable blood pressure” requires both a systolic value below the 90th percentile and a diastolic value below the 90th percentile; “prehypertension” requires systolic value in the 90th to below the 95th percentile and/or diastolic value in the 90th to below the 95th percentile; “hypertension” requires systolic value in the 95th to below the 99th percentile and/or diastolic value in the 95th to below the 99th percentile; “severe hypertension” requires systolic value in the 99th percentile or above and/or diastolic value in the 99th percentile or above.

      2.6 Classification of metabolic syndrome

      Because there are no standardized criteria for diagnosis of the metabolic syndrome in children or adolescents, we adapted guidelines from the National Cholesterol Education Program's Adult Treatment Panel III [
      • Executive summary of the third report of the National Cholesterol Education Program (NCEP)
      Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
      ] and the World Health Organization [
      • Alberti K.G.
      • Zimmet P.Z.
      Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.
      ]. Age- and sex-specific algorithms provided by the CDC were also used for classification of hyperinsulinemia and lipids. The subjects in our study were classified as having the metabolic syndrome if 3 of more of the following criteria were met: (1) systolic or diastolic blood pressure greater than the 90th percentile; (2) BMI above the 95th percentile; (3) TG in excess of the 95th percentile; (4) HDL below the 5th percentile; and (5) fasting glucose ≥110 mg/dL or fasting insulin ≥75th percentile. These criteria have been used in previous studies of the metabolic syndrome [
      • Weiss R.
      • Dziura J.
      • Burgert T.S.
      • et al.
      Obesity and the metabolic syndrome in children and adolescents.
      ,
      • de Ferranti S.D.
      • Gauvreau K.
      • Ludwig D.S.
      • et al.
      Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey.
      ,
      • Lakka H.M.
      • Laaksonen D.E.
      • Lakka T.A.
      • et al.
      The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.
      ].

      2.7 Statistical analysis

      Statistical analyses were performed with GraphPad Prism (GraphPad, San Diego, CA) and SAS software (version 8.2, SAS Institute, Cary, NC). Pre- and postintervention values were compared using matched-pair t tests. Correlations were tested by determining Pearson correlation coefficients. All data are expressed as mean ± SEM unless otherwise noted. A P value of less than .05 was considered statistically significant.

      3. Results

      3.1 Physical Characteristics, blood pressure, serum lipids, glucose, and insulin

      Anthropometric and metabolic data are summarized in Table 1. The mean BMI of 33.2 ± 1.9 kg/m2 for the subjects at baseline indicates that, on average, these children were overweight (>95th percentile according to CDC BMI standards) at the commencement of the program. All subjects had a BMI above the 75th percentile and 11 of the 16 were at risk (>85th percentile) or overweight (>95th percentile) according to CDC BMI standards. The mean baseline percentage body fat of 37.5% ± 1.1% combined with a mean 103.3 ± 5.5 cm waist circumference suggests central adiposity, with excessive total body fat at the beginning of the program. After the 2-week intervention, body weight (Fig. 1A ), BMI, waist circumference, and percentage body fat were all reduced significantly (P ≤ .01), although the subjects remained overweight because of the brevity of the intervention. Correlation analyses indicated no significant correlation between change in BMI or body weight and any of the parameters measured (all R2 < 0.1).
      Table 1Anthropometric and metabolic parameters in children undergoing a 14-day diet and exercise intervention
      ParameterPreinterventionPostintervention% Decrease
      Body weight (kg)92.0 ± 7.088.0 ± 6.84.3
      P < .01.
      BMI (kg/m2)33.2 ± 1.931.8 ± 1.94.3
      P < .01.
      Body fat (%)37.5 ± 1.136.4 ± 1.23.0
      P < .01.
      Waist circumference (cm)103.3 ± 5.598.3 ± 3.34.8
      P < .05.
      Systolic blood pressure (mm Hg)130 ± 3.1117 ± 1.810.4
      P < .01.
      Diastolic blood pressure (mm Hg)74.3 ± 3.067.2 ± 2.310.6
      P < .05.
      Resting heart rate (beats per minute)88 ± 2.978 ± 3.011.6
      P < .05.
      Total cholesterol (mg/dL)165 ± 7.8127 ± 7.423.3
      P < .01.
      HDL cholesterol (mg/dL)42.3 ± 2.440.8 ± 3.03.4
      LDL cholesterol (mg/dL)94.1 ± 8.268.5 ± 6.725.3
      P < .01.
      Total cholesterol/HDL cholesterol4.16 ± 0.303.34 ± 0.3019.8
      P < .01.
      LDL cholesterol/HDL cholesterol2.27 ± 0.291.78 ± 0.2322.9
      P < .01.
      Triglycerides (mg/dL)146 ± 16.288.1 ± 8.139.5
      P < .01.
      Blood glucose (mg/dL)82.5 ± 2.388.3 ± 1.5−7.1
      P < .05.
      Insulin (μU/mL)27.2 ± 3.418.3 ± 1.732.6
      P < .01.
      HOMA-IR5.79 ± 0.814.13 ± 0.3828.6
      P < .05.
      QUICKI0.304 ± 0.0060.313 ± 0.004−3.04
      Mean anthropometric and metabolic measures of overweight youth undergoing a 14-day diet and exercise intervention. All data are expressed as mean ± SEM.
      low asterisk P < .05.
      low asterisklow asterisk P < .01.
      Figure thumbnail gr1
      Fig. 1A, Before-and-after plot of bodyweight in overweight youth (n = 16) undergoing a 14-day diet and exercise intervention. B, Before-and-after plot of systolic blood pressure percentiles adjusted for age, sex, and race. Shaded portion indicates 90th percentile and above. C, Before-and-after plot of serum triglycerides. D, Before-and-after plot of LDL cholesterol. E, Before-and-after plot of HDL cholesterol. F, Before-and-after plot of serum insulin.
      Using the 90th percentile standard set by the National Heart, Lung, and Blood Institute [
      National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.
      ] for either systolic or diastolic blood pressure as the definition for prehypertension, 9 of 16 subjects were prehypertensive or hypertensive before intervention. After intervention, decreases in systolic (10.4%, P < .001) and diastolic (10.6%, P = .01) blood pressure were observed, with 8 of the 9 subjects with elevated blood pressure exhibiting blood pressures in the normotensive range (Fig. 1B). In addition, resting heart rate decreased by 11.6% postintervention.
      All serum lipids improved significantly (>20% decreases, P < .01, Table 1, Fig. 1C and D), with the exception of HDL, which showed no significant change (Fig. 1E). Fasting insulin level decreased significantly (32.6%, P < .01, Fig. 1F) after the program. Although blood glucose increased significantly (P = .01) postintervention, HOMA-IR, a surrogate of insulin resistance, improved significantly postintervention (P < .01). The QUICKI improved after treatment, although it did not reach statistical significance (P = .08).
      Table 2 indicates the number of children in the study classified as having elevated risk factors and the metabolic syndrome, according to criteria modified from the National Cholesterol Education Program's Adult Treatment Panel III [
      • Executive summary of the third report of the National Cholesterol Education Program (NCEP)
      Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
      ] and the World Health Organization [
      • Alberti K.G.
      • Zimmet P.Z.
      Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.
      ]. Before the intervention, 7 of the 16 children were classified as having the metabolic syndrome, and at departure, none were classified as having the metabolic syndrome.
      Table 2Prevalence of metabolic syndrome pre- and postintervention
      ParameterPreinterventionPostintervention
      Elevated blood pressure (SBP or DBP >90th percentile)91
      BMI >95th percentile77
      Triglycerides >95th percentile70
      HDL <5th percentile14
      Fasting glucose ≥110 mg/dL or insulin ≥75th percentile93
      Subjects with the metabolic syndrome (≥3 risk factors)70
      Number of overweight children and adolescents possessing risk factors for the metabolic syndrome before and after the 14-day diet and exercise intervention.

      4. Discussion

      Westernized societies have seen a rapid rise in obesity rates in recent years, with a concomitant increase of children exhibiting characteristics of the metabolic syndrome [
      • Vincent S.D.
      • Pangrazi R.P.
      • Raustorp A.
      • et al.
      Activity levels and body mass index of children in the United States, Sweden, and Australia.
      ,
      • James P.T.
      • Rigby N.
      • Leach R.
      The obesity epidemic, metabolic syndrome and future prevention strategies.
      ,
      • Deckelbaum R.J.
      • Williams C.L.
      Childhood obesity: the health issue.
      ]. Previous studies in adult populations using similar diet and exercise protocols resulted in significant improvements in body weight, BMI, serum lipids, glucose, insulin, inflammatory markers, oxidative stress, and adhesion molecule expression [
      • Wegge J.K.
      • Roberts C.K.
      • Ngo T.H.
      • et al.
      Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease.
      ,
      • Roberts C.K.
      • Vaziri N.D.
      • Barnard R.J.
      Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability.
      ,
      • Barnard R.J.
      Effects of life-style modification on serum lipids.
      ]. Accordingly, the present study was designed to investigate the effects of a structured diet and exercise program on the metabolic syndrome in young subjects. The major new finding is the rapid reversal of metabolic syndrome with a short, residential diet and activity intervention.
      The serum lipid profile improved significantly for all measures with the exception of HDL, which did not change. These reductions in lipids are in accordance with studies of adults attending this residential program, except that HDL decreases in adults [
      • Wegge J.K.
      • Roberts C.K.
      • Ngo T.H.
      • et al.
      Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease.
      ,
      • Roberts C.K.
      • Vaziri N.D.
      • Barnard R.J.
      Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability.
      ,
      • Barnard R.J.
      Effects of life-style modification on serum lipids.
      ]. The low saturated fat, trans fat, and cholesterol content of the diet and high fiber intake are likely responsible for the decrease in total cholesterol and LDL. The high levels of physical activity and relatively low baseline levels of HDL likely played a role in the maintenance of their HDL levels. In addition, it has been suggested that ratios of total cholesterol/HDL and LDL/HDL are better predictors of CAD risk reduction than HDL, LDL, or total cholesterol values alone [
      • Kinosian B.
      • Glick H.
      • Garland G.
      Cholesterol and coronary heart disease: predicting risks by levels and ratios.
      ,
      • Wang T.-D.
      • Chen W.-J.
      • Chien K.-L.
      • et al.
      Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population.
      ,
      • Natarajan S.
      • Glick H.
      • Criqui M.
      • et al.
      Cholesterol measures to identify and treat individuals at risk for coronary heart disease.
      ]. Evidence supporting this idea comes from data in populations after very low-fat diets with reduced cardiovascular disease risk, despite low HDL concentrations [
      • Connor W.E.
      • Cerqueira M.T.
      • Connor R.W.
      • et al.
      The plasma lipids, lipoproteins, and diet of the Tarahumara Indians of Mexico.
      ].
      The marked improvement observed in serum TG is primarily due to the combination of the high-fiber, unrefined-carbohydrate diet and the regular physical activity. Because consumption of processed carbohydrates is generally high in obese children [
      • St-Onge M.-P.
      • Keller K.L.
      • Heymsfield S.B.
      Changes in childhood food consumption patterns: a cause for concern in light of increasing body weights.
      ], the transition to a diet largely devoid of refined carbohydrates, along with a daily exercise regimen [
      • Oscai L.B.
      • Patterson J.A.
      • Bogard D.L.
      • et al.
      Normalization of serum triglycerides and lipoprotein electrophoretic patterns by exercise.
      ], facilitated the reduction of TG. In addition, the decrease in serum insulin may also play a role in reducing TG.
      Insulin resistance, thought to be at least partially modulated by visceral and intramuscular lipid accumulation [
      • Weiss R.
      • Dufour S.
      • Taksali S.E.
      • et al.
      Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning.
      ,
      • Krssak M.
      • Petersen K.F.
      • Dresner A.
      • et al.
      Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.
      ,
      • Montague C.
      • O'Rahilly S.
      The perils of portliness: causes and consequences of visceral adiposity.
      ], is hypothesized to be an underlying cause for the other risk factors of the metabolic syndrome [
      • DeFronzo R.A.
      • Ferrannini E.
      Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.
      ]. In the present study, we noted a small rise in fasting glucose (7.1%) accompanied by a much larger decrease in insulin (32.6%) after the diet and exercise intervention. Because our subjects began treatment with normal baseline glucose concentrations, decreases were not expected. Nevertheless, HOMA-IR decreased significantly, suggestive of an increase in insulin sensitivity (Table 1). Previous studies in overweight children after regular exercise programs report improvements in fasting insulin [
      • Ferguson M.A.
      • Gutin B.
      • Le N.A.
      • et al.
      Effects of exercise training and its cessation on components of the insulin resistance syndrome in obese children.
      ,
      • Kang H.S.
      • Gutin B.
      • Barbeau P.
      • et al.
      Physical training improves insulin resistance syndrome markers in obese adolescents.
      ], whereas a combined diet (nutritionist visits) and 3 d/wk of aerobic exercise improved HOMA-IR in overweight subjects [
      • Balagopal P.
      • George D.
      • Patton N.
      • et al.
      Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents.
      ]. The factors responsible for the changes in insulin in our subjects are likely because of improved insulin sensitivity from increased physical activity and the low-glycemic load of the diet. For example, low glycemic-load diets are associated with improvements in postprandial glucose, insulin, and lipids [
      • Jenkins D.J.
      • Popovich D.G.
      • Kendall C.W.
      • et al.
      Effect of a diet high in vegetables, fruit, and nuts on serum lipids.
      ,
      • Wolever T.M.
      • Mehling C.
      Long-term effect of varying the source or amount of dietary carbohydrate on postprandial plasma glucose, insulin, triacylglycerol, and free fatty acid concentrations in subjects with impaired glucose tolerance.
      ]. Exercise is known to increase insulin receptor autophosphorylation, glucose transporter 4 expression, and glucose transport [
      • Youngren J.F.
      • Keen S.
      • Kulp J.L.
      • et al.
      Enhanced muscle insulin receptor autophosphorylation with short-term aerobic exercise training.
      ,
      • Vukovich M.D.
      • Arciero P.J.
      • Kohrt W.M.
      • et al.
      Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners.
      ,
      • Perseghin G.
      • Price T.B.
      • Petersen K.F.
      • et al.
      Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects.
      ].
      Elevated blood pressure is well recognized as a risk factor for coronary events in adults [
      • Ivanusa M.
      • Ivanusa Z.
      Risk factors and in-hospital outcomes in stroke and myocardial infarction patients.
      ]. Overweight in children is associated with arterial endothelial dysfunction, which is a hallmark of elevated blood pressure [
      • Woo K.S.
      • Chook P.
      • Yu C.W.
      • et al.
      Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening.
      ]. Of the 16 subjects, 9 had elevated blood pressure before the diet and exercise intervention, and all but 1 became normotensive after the program. Both systolic and diastolic blood pressures changed significantly postintervention, with ~10% reductions in each measure. Because the postintervention blood pressure was taken after more than 12 hours after the last exercise bout and after an overnight fast, this reduction is likely independent of the acute hypotensive effect of exercise [
      • Pescatello L.S.
      • Kulikowich J.M.
      The aftereffects of dynamic exercise on ambulatory blood pressure.
      ]. Potential mechanisms responsible for this change may include increased endothelial nitric oxide synthase activity, decreased sympathetic nervous system activation, decreased renin activity, and increased insulin sensitivity [
      • Roberts C.K.
      • Vaziri N.D.
      • Barnard R.J.
      Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability.
      ,
      • Koga M.
      • Ideishi M.
      • Matsusaki M.
      • et al.
      Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals.
      ,
      • Scherrer U.
      • Sartori C.
      Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity.
      ,
      • Arakawa K.
      Exercise, a measure to lower blood pressure and reduce other risks.
      ]. Our findings are supported by Woo et al [
      • Woo K.S.
      • Chook P.
      • Yu C.W.
      • et al.
      Effects of diet and exercise on obesity-related vascular dysfunction in children.
      ] who noted significant improvements in arterial endothelial function after a 1-year diet and exercise program in overweight children. Although the diet and exercise regimen was less stringent compared with that of our study, it illustrates the efficacy and sustainability of such a program in young individuals.
      The subjects were not engaging in regular physical activity on a regular basis before the intervention and, thus, the high baseline resting heart rate and 11% reduction in resting heart rate in 2 weeks reflects low initial fitness coupled with adaptations to the exercise activities. This reduction was noted despite the lack of monitoring intensity during exercise. Resting heart rate is a reliable indicator of cardiovascular fitness, is positively correlated with cardiovascular mortality in adults [
      • Kannel W.B.
      • Kannel C.
      • Paffenbarger Jr., R.S.
      • et al.
      Heart rate and cardiovascular mortality: the Framingham Study.
      ,
      • Gillum R.F.
      • Makuc D.M.
      • Feldman J.J.
      Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study.
      ,
      • Filipovsky J.
      • Ducimetiere P.
      • Safar M.E.
      Prognostic significance of exercise blood pressure and heart rate in middle-aged men.
      ], and is strongly associated with hypertension [
      • Filipovsky J.
      • Ducimetiere P.
      • Safar M.E.
      Prognostic significance of exercise blood pressure and heart rate in middle-aged men.
      ,
      • Palatini P.
      • Julius S.
      Heart rate and the cardiovascular risk.
      ].
      The major finding of this investigation is that all 7 subjects classified with the metabolic syndrome at baseline were no longer classified as such after treatment, despite remaining overweight. The improvements in TG, blood pressure, and insulin were primarily responsible for the amelioration of the syndrome. Because pediatric obesity has increased since 1994 [
      • Ogden C.L.
      • Flegal K.M.
      • Carroll M.D.
      • et al.
      Prevalence and trends in overweight among US children and adolescents, 1999-2000.
      ], the prevalence of the metabolic syndrome in the youth is likely to be greater than current estimates. Furthermore, Weiss et al [
      • Weiss R.
      • Dziura J.
      • Burgert T.S.
      • et al.
      Obesity and the metabolic syndrome in children and adolescents.
      ] reported that the greater the degree of overweight in children, the greater the prevalence of the metabolic syndrome, whereas Brage et al [
      • Brage S.
      • Wedderkopp N.
      • Ekelund U.
      • et al.
      Features of the metabolic syndrome are associated with objectively measured physical activity and fitness in Danish children: the European Youth Heart Study (EYHS).
      ] noted that cardiovascular fitness varied inversely with metabolic syndrome risk. This information, combined with reports that the metabolic syndrome phenotype tends to persist and worsen over time if no preventive actions are taken [
      • Weiss R.
      • Dziura J.
      • Burgert T.S.
      • et al.
      Obesity and the metabolic syndrome in children and adolescents.
      ], highlights the value of diet and exercise intervention to mitigate the increase in the population at risk. In addition, Sudi et al [
      • Sudi K.M.
      • Gallistl S.
      • Trobinger M.
      • et al.
      The effects of changes in body mass and subcutaneous fat on the improvement in metabolic risk factors in obese children after short-term weight loss.
      ], using a restrictive diet (~4.602 kJ/d [~1100 kcal/d]) and substantially more physical activity (4.5 h/d), documented reduced total cholesterol, TG, body weight, and insulin in overweight children over a 3-week span. We suggest that the ad libitum diet and lower amount of physical activity may be more sustainable in this population and thus suggest that energy restriction and large volumes of exercise are not required to achieve significant metabolic benefits. In addition, Kelly et al [
      • Kelly A.S.
      • Wetzsteon R.J.
      • Kaiser D.R.
      • et al.
      Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise.
      ] noted modest improvements in blood pressure, HDL, insulin, and flow-mediated dilation in overweight children and adolescents with exercise alone, suggesting that superior results are achieved for many variables, that is, lipid reductions and C-reactive protein reductions (Roberts et al, unpublished data) when a combined intervention is used.
      The current study has important strengths and limitations to consider. The major strength of the study is the monitoring permitted by the study. Monitoring food intake and physical activity reduces the need to query subjects about their compliance or to rely on food and activity questionnaires. Furthermore, all exercise sessions were supervised, and adherence to the diet and activities was essentially 100%. On the other hand, further studies must assess the ability of these changes to be durable in children in a home environment, as has been shown in adults previously [
      • Barnard R.J.
      Effects of life-style modification on serum lipids.
      ]. Furthermore, we do not know the degree of dietary change, given that baseline dietary intake was not assessed. In addition, the study was not a randomized, controlled trial, and the results support the need for larger, randomized, controlled investigations. The present study was not designed to investigate the independent effects of diet and physical activity and, thus, cannot discern which aspect(s) of the intervention were responsible for the changes noted, nor can we assess whether the weight loss or the diet and activity per se induced the changes noted. However, changes in body composition did not correlate significantly with metabolic changes. Because we did not assess dietary intake before the study, we can only comment on the dietary components that the average American consumes. For example, the subjects consumed a minimum of 4 vegetables and 3 fruit servings per day, which is significantly greater than the average reported in 1 study in normal-weight children (BMI = 20) of approximately 2.3 vegetables and 0.85 fruit servings per day. In this report, only 5% and 20% of children met the former US Department of Agriculture Food Guide Pyramid recommendations for fruits and vegetables, respectively [
      • Brady L.M.
      • Lindquist C.H.
      • Herd S.L.
      • et al.
      Comparison of children's dietary intake patterns with US dietary guidelines.
      ]. In addition, data from the Continuing Survey of Food Intakes by Individuals suggests that fruits are the most commonly omitted food group, intakes of specific types of vegetables (ie, dark green, deep yellow) and of whole grains are well below that recommended, whereas intakes of total fat and added sugars exceed current recommendations. Data suggest that diets of most of the population require improvement [
      • Dixon L.B.
      • Cronin F.J.
      • Krebs-Smith S.M.
      Let the pyramid guide your food choices: capturing the total diet concept.
      ].
      In summary, the results of this study document that dramatic reductions in the incidence of metabolic syndrome and its associated factors in children can be achieved in a very short period through changes in diet and exercise alone. Our data are the first to document significant improvement in the metabolic syndrome in less than 3 weeks. Not only are obesity and physical inactivity associated with each other [
      • Vincent S.D.
      • Pangrazi R.P.
      • Raustorp A.
      • et al.
      Activity levels and body mass index of children in the United States, Sweden, and Australia.
      ,
      • Graf C.
      • Koch B.
      • Kretschmann-Kandel E.
      • et al.
      Correlation between BMI, leisure habits and motor abilities in childhood (CHILT-project).
      ], they are important factors that carry over into adulthood and increase the risk for CAD and future chronic diseases. It is important to note that these improvements were achieved, in part, with a diet that limited only refined-carbohydrate, fat, sodium, and animal-derived products. The low energy density and high-fiber content of the diet provided sufficient bulk to ensure satiety and a net negative energy balance, when combined with daily exercise. If sustained, lifestyle modification can help mitigate chronic disease-related complications in the future. Given the challenge of implementing lifestyle changes in children and adolescents, future studies should investigate how youth and their families can incorporate and sustain these changes into their lives.

      Acknowledgment

      This study was supported by a grant from the L-B Research/ Education Foundation and funding from UCLA. Christian Roberts was supported by a National Research Scholarship Award postdoctoral fellowship, NIH F32 HL68406-01, during this project. This study was not funded by the Pritikin Longevity Center.

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