Do Obese Children Have Chronic Inflammation & Could This Contribute to Future CVD Risk?

Current Cardiovascular Risk Reports

Volumn 6, Issue 6, 2012, Pages 579-590

  Satchell, Marlon D ^a   Mann, Karl J ^b  

^a JEFFERSON COLLEGE OF POPULATION HEALTH   (United States)

^b Babu)   (United States)

Author keywords

Atherosclerosis, Subclinical inflammation; Cardiovascular disease (CVD); Children; Obesity; Thrombosis, Coagulation, Adipokines, Cytokines, Intervention, Lifestyle, Physical activity, Puberty

Indexed keywords

ACUTE PHASE PROTEIN; ADIPOCYTOKINE; ADIPONECTIN; C REACTIVE PROTEIN; CYTOKINE; FIBRINOGEN; I KAPPA B KINASE INHIBITOR; INTERCELLULAR ADHESION MOLECULE 1; LEPTIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; RETINOL BINDING PROTEIN 4; SERUM AMYLOID A; STRESS ACTIVATED PROTEIN KINASE; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1; VON WILLEBRAND FACTOR;

ADIPOCYTE; ADIPOSE TISSUE; BLOOD CLOTTING; BODY COMPOSITION; BODY MASS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHILD; CHRONIC INFLAMMATION; COMORBIDITY; ENERGY EXPENDITURE; ERYTHROCYTE SEDIMENTATION RATE; HUMAN; INSULIN RESISTANCE; LEUKOCYTE; LIFESTYLE MODIFICATION; OBESITY; PATHOGENESIS; REVIEW; SOCIAL STATUS;

EID: 84873419665     PISSN: 19329520     EISSN: 19329563     Source Type: Journal    
DOI: 10.1007/s12170-012-0271-z     Document Type: Review

References (101)

1. Ogden CL, Carroll M, Kit B, Flegal K. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA. 2012; 307: 483-90.
2. •• Daniels SR, Pratt CA, Hayman LL. Reduction of risk for cardiovascular disease in children and adolescents. Circulation. 2011; 124: 1673-86. This is a nice summary of the evidence and the current published recommendations regarding the epidemiology of risk factors (mainly traditional) for atherosclerotic CVD in childhood. The authors have also outlined the recommended clinical approaches to prevent risk factor development and review cut points for identifying risk factors and approaches for ameliorating high-risk status once it has developed.
3. •• Juonala M, Magnussen CG, Berenson GS, et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med. 2011; 365: 1876-85. Here the authors analyzed data from four prospective cohort studies and showed that persons who had normal BMI in childhood but who became obese as adults had adverse risk-factor profiles, whereas those who were overweight or obese as children but who became non-obese as adults had a cardiovascular-risk profile that was similar to that of persons who were never obese. Although the study did not include any nontraditional risk factors for CVD, the clinical, research and therapeutic implications of this study are significant.
4. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005; 115: 1111-9.
5. Gregor MF. Hotamisligil G. k. S. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011; 29: 415-45.
6. •• Steinberger J, Daniels SR, Eckel RH, et al. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American heart association atherosclerosis, hypertension, and obesity in the young committee of the council on cardiovascular disease in the young; council on cardiovascular nursing; and council on nutrition, physical activity, and metabolism. Circulation. 2009; 119: 628-47. This AHA-statement paper is comprehensive account of the progress and challenges related to metabolic syndrome and risk factors for CVD in children.
7. •• Balagopal P, de Ferranti SD, Cook S, et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation. 2011; 123: 2749-69. This AHA-statement paper provides a comprehensive account of the current state of science of traditional and nontraditional risk factors/biomarkers with emphasis on those related to insulin resistance, oxidative stress and inflammation and potential cross talk between organs in regulating these risk factors.
8. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11: 85-97.
9. Libby P, Ridker PM. Inflammation and atherosclerosis: role of CRP in risk assessment. Am J Med. 2004; 116: 9S-16S.
10. Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008; 54: 24-38.
11. Hummasti S, Hotamisligil GS. Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ Res. 2010; 107: 579-91.
12. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011; 473: 317-25.
13. Ford ES. C-reactive protein concentration and cardiovascular disease risk factors in children: findings from the national health and nutrition examination survey 1999-2000. Circulation. 2003; 108: 1053-8.
14. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003; 107: 499-511.
15. Cook DG, Mendall MA, Whincup PH, et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis. 2000; 149: 139-50.
16. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris JB. Low-grade systemic inflammation in overweight children. Pediatrics. 2001; 107: E-13.
17. Ford ES, 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, 1988-1994. J Pediatr. 2001; 138: 486-92.
18. Zieske AW, Tracy RP, McMahan CA, et al. Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol. 2005; 25: 1237-43.
19. •• Dowd JB, Zajacova A, Aiello AE. Predictors of Inflammation in U. S. Children aged 3-16 years. Am J Prev Med. 2010; 39: 314-20. This study examined the physical and social risk correlates of C-reactive protein concentrations in > 6000 children aged 3 to 16 in a nationally representative sample of U. S. children (NHANES 1999-2004). The authors conclude that increased adiposity is associated with higher CRP concentrations in U. S children aged 3-16 years, and both socioeconomic and race/ethnic differences exist in systemic inflammation in this cohort.
20. Vikram NK, Misra A, Dwivedi M, et al. Correlations of C-reactive protein levels with anthropometric profile, percentage of body fat and lipids in healthy adolescents and young adults in urban North India. Atherosclerosis. 2003; 168: 305-13.
21. Juonala M, Viikari JSA, Ronnemaa T, Taittonen L, Marniemi J, Raitakari OT. Childhood C-reactive protein in predicting CRP and carotid intima-media thickness in adulthood: the cardiovascular risk in young Finns study. Arterioscler Thromb Vasc Biol. 2006; 26: 1883-8.
22. Jarvisalo MJ, Harmoinen A, Hakanen M, et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol. 2002; 22: 1323-8.
23. Grundy SM, Garber A, Goldberg R, et al. Prevention conference VI: diabetes and cardiovascular disease: writing group IV: lifestyle and medical management of risk factors. Circulation. 2002; 105: e153-8.
24. Haddy N, Sass C, Droesch S, et al. IL-6, TNF-a and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis. 2003; 170: 277-83.
25. Desideri G, De Simone M, Iughetti L, et al. Early activation of vascular endothelial cells and platelets in obese children. J Clin Endocrinol Metab. 2005; 90: 3145-52.
26. de Ferranti SD, Gauvreau K, Ludwig DS, Newburger JW, Rifai N. Inflammation and changes in metabolic syndrome abnormalities in US adolescents: findings from the 1988-1994 and 1999-2000 National Health and nutrition examination surveys. Clin Chem. 2006; 52: 1325-30.
27. Balagopal P, George D, Patton N, et al. Lifestyle-only intervention attenuates the inflammatory state associated with obesity - a randomized controlled study in adolescents. J Pediatr. 2005; 146: 342-8.
28. Kelly AS, Wetzsteon RJ, Kaiser DR, Steinberger J, Bank AJ, Dengel DR. Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise. J Pediatr. 2004; 145: 731-6.
29. Ford ES, Gillespie C, Ballew C, Sowell A, Mannino DM. Serum carotenoid concentrations in US children and adolescents. Am J Clin Nutr. 2002; 76: 818-27.
30. Sinaiko AR, Steinberger J, Moran A, et al. Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation. 2005; 111: 1985-91.
31. Giannini C, de Giorgis T, Scarinci A, et al. Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children. Atherosclerosis. 2008; 197: 448-56.
32. •• Mauras N, DelGiorno C, Hossain J, et al. Metformin Use in children with obesity and normal glucose tolerance - effects on cardiovascular markers and intrahepatic fat. J Pediatr Endocrinol Metab. 2012; 25: 33-40. This study showed physical activity-induced reduction in elevated levels of thrombotic and inflammatory factors. Further it showed that addition of metformin to the physical activity-based intervention did not enhance the beneficial changes in these factors elicited through physical activity alone, despite improved weight loss. The study also reported profound changes in intrahepatic fat in response to the physical activity-based intervention.
33. • Parrett AL, Valentine RJ, Arngrimsson SA, Castelli DM, Evans EM. Adiposity, activity, fitness, and C-reactive protein in children. Med Sci Spor Exer. 2010; 42. In this study the authors reported a relationship between adiposity (DEXA) and CRP in prepubascent children, independent of the effects of fitness or physical activity. Further physical acitivity (pedometers) was inversely associated with CRP levels in this cohort.
34. •• Skinner A. C., Steiner M. J., Henderson F. W., Perrin E. M. Multiple Markers of Inflammation and Weight Status: Cross-sectional Analyses Throughout Childhood. Pediatrics 2010; eds. This study demonstrated a strong and consistent association among multiple inflammatory markers and obesity in a in a large, recent nationally representative sample of US children from the NHANES data set (years 1999-2006). Although associations between inflammatory markers and obesity were greatest for older children, this relationship was observed among children as young as age 3.
35. Sattar N, McConnachie A, O'Reilly D, et al. Inverse Association Between Birth Weight and C-Reactive Protein Concentrations in the MIDSPAN Family Study. Arterioscler Thromb Vasc Biol. 2004; 24: 583-7.
36. Tzoulaki I, Jarvelin MR, Hartikainen AL, et al. Size at birth, weight gain over the life course, and low-grade inflammation in young adulthood: northern Finland 1966 birth cohort study. Eur Heart J. 2008; 29: 1049-56.
37. •• Lakshmy R, Fall CH, Sachdev HS, et al. Childhood body mass index and adult pro-inflammatory and pro-thrombotic risk factors: data from the New Delhi birth cohort. Int J Epidemiol. 2011; 40: 102-11. In this longitudinal birth cohort study the authors demonstrate that thinness at birth and/or in infancy was associated with higher fibrinogen, CRP and PAI-1 in adulthood (after ~21 years.
38. •• Nazmi A, Gonzalez DC, Oliveira IO, Horta BL, Gigante DP, Victora CG. Life course weight gain and C-reactive protein levels in young adults: findings from a Brazilian birth cohort. Am J Hum Biol. 2009; 21: 192-9. The authors report relationship between life course weight gain and CRP levels in this longitudinal Brazilian birth cohort study.
39. •• Norris AL, Steinberger J, Steffen LM, Metzig AM, Schwarzenberg SJ, Kelly AS. Circulating oxidized LDL and inflammation in extreme pediatric obesity. Obesity. 2011; 19: 1415-9. Data on CVD risk factors in extreme pediatric obesity is scarce. This cross-sectional study reports that extreme pediatric obesity, compared to milder forms of obesity and normal weight, is associated with high levels of CRP and oxidized-LDL.
40. Gomez-Ambrosi J, Azcona C, Patino-Garcia A, Frnhbeck G. Serum amyloid A concentration is increased in obese children and adolescents. J Pediatr. 2008; 153: 71-5.
41. •• Tam CS, Clement K, Baur LA, Tordjman J. Obesity and low-grade inflammation: a paediatric perspective. Obesity Rev. 2010; 11: 118-26. This is an excellent review on obesity-driven inflammation in the pediatric population.
42. Robertson K, Adolfsson P, Scheiner G, Hanas R, Riddell MC. Exercise in children and adolescents with diabetes. Pediatr Diabetes. 2009; 10: 154-68.
43. Caballero AE, Bousquet-Santos K, Robles-Osorio L, et al. Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body Fat and insulin resistance. Diabetes Care. 2008; 31: 576-82.
44. Sundaram SS, Zeitler P, Nadeau K. The metabolic syndrome and nonalcoholic fatty liver disease in children. Curr Opin Pediatr. 2009; 21.
45. Nagel G, Rapp K, Wabitsch M, et al. Prevalence and cluster of cardiometabolic biomarkers in overweight and obese schoolchildren: results from a large survey in southwest Germany. Clin Chem. 2008; 54: 317-25.
46. Kapiotis S, Holzer G, Schaller G, et al. A proinflammatory state is detectable in obese children and is accompanied by functional and morphological vascular changes. Arterioscler Thromb Vasc Biol. 2006; 26: 2541-6.
47. Maffeis C, Silvagni D, Bonadonna R, Grezzani A, Banzato C, Tat L. Fat cell size, insulin sensitivity, and inflammation in obese children. J Pediatr. 2007; 151: 647-52.
48. Gallistl S, Sudi KM, Aigner R, Borkenstein M. Changes in serum interleukin-6 concentrations in obese children and adolescents during a weight reduction program. Int J Obes. 2001; 25: 1640-3.
49. Jimenez MV, Estepa RM, Camacho RM, Estrada RC, Luna FG, Guitarte FB. Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children. Eur J Endocrinol. 2007; 156: 497-502.
50. Dixon D, Goldberg R, Schneiderman N, Delamater A. Gender differences in TNF-[alpha] levels among obese vs nonobese Latino children. Eur J Clin Nutr. 2004; 58: 696-9.
51. Nemet D, Oh Y, Kim HS, Hill M, Cooper DM. Effect of intense exercise on inflammatory cytokines and growth mediators in adolescent boys. Pediatrics. 2002; 110: 681-9.
52. Masquio DC, de Piano A, Sanches PL, et al. The effect of weight loss magnitude on pro/anti-inflammatory adipokines and carotid intima-media thickness in obese adolescents engaged in interdisciplinary weight-loss therapy. Clin Endocrinol (Oxf). 2012. doi: 10. 1111/j. 1365-2265. 2012. 04504. x.
53. •• Balagopal P, Gidding SS, Buckloh LM, et al. Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study. Obesity. 2010; 18: 1747-53. This randomized controlled physical activity-based lifestyle intervention study showed strong relationship between leptin (and other satiety hormones) and inflammatory factors in adolescents. More importantly the study demonstrated a reduction in leptin along with concomitant reductions in inflammatory factors even without absolute weight loss, but with a beneficial redistribution of body composition parameters.
54. Spruijt-Metz D, Adar Emken B, Spruijt MR, et al. CRP is related to higher leptin levels in minority peripubertal females regardless of adiposity levels. Obesity. 2012; 20: 512-6.
55. Stringer DM, Sellers EA, Burr LL, Taylor CG. Altered plasma adipokines and markers of oxidative stress suggest increased risk of cardiovascular disease in First Nation youth with obesity or type 2 diabetes mellitus. Pediatr Diabetes. 2009; 10: 269-77.
56. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004; 350: 2362-74.
57. •• Buchan DS, Thomas NE, Baker JS. Novel risk factors of cardiovascular disease and their associations between obesity, physical activity and physical fitness. J Pub Health Res. 2012; 1: 59-66. This is an excellent review of novel risk factors of CVD, especially focussing on sub-clinical inflammation in pediatric obesity. The review also discussed the potential role of physical activity and physical fitness in attenuating the pro-inflammatory state related to obesity in the pediatric population.
58. Winer JC, Zern TL, Taksali SE, et al. Adiponectin in childhood and adolescent obesity and its association with inflammatory markers and components of the metabolic syndrome. J Clin Endocrinol Metab. 2006; 91: 4415-23.
59. Jeffery AN, Murphy MJ, Metcalf BS, et al. Adiponectin in childhood. Int J Pediatr Obesity. 2008; 6: 1-11.
60. Araki S, Dobashi K, Kubo K, Asayama K, Shirahata A. High molecular weight, rather than total, adiponectin levels better reflect metabolic abnormalities associated with childhood obesity. J Clin Endocrinol Metab. 2006; 91: 5113-6.
61. Ibanez L, Lopez-Bermejo A, Diaz M, Angulo M, Sebastiani G, de Zegher F. High-molecular-weight adiponectin in children born small- or appropriate-for-gestational-age. J Pediatr. 2009; 155: 740-2.
62. Nishimura R, Morimoto A, Matsudaira T, et al. Ratio of high-, medium-, and Low-molecular weight serum adiponectin to the total adiponectin value in children. J Pediatr. 2007; 151: 545-7.
63. •• Martos-Moreno GA, Barrios V, Martinez G, Hawkins F, Argente J. Effect of weight loss on high-molecular weight adiponectin in obese children. Obesity. 2010; 18: 2288-94. In this study the authors determined the effect of weight reduction on total and high molecular weight adiponectin in obese prepubertal children. Quite surprisingly and contrary to most reports, they demonstrated increased levels of total adiponectin in obese prepubertal children compared to lean controls. However, weight reduction increased the concentration of both total adiponectin and HMW adiponectin and reduced leptin, TNF-α and IL-6.
64. Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005; 436: 356-62.
65. Graham TE, Yang Q, Bluher M, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med. 2006; 354: 2552-63.
66. Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab. 2007; 92: 1971-4.
67. Lee DC, Lee JW, Im JA. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents. Metabolism. 2007; 56: 327-31.
68. Reinehr T, Stoffel-Wagner B, Roth CL. Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss. J Clin Endocrinol Metab. 2008; 93: 2287-93.
69. Aeberli I, Biebinger R, Lehmann R, L'Allemand D, Spinas GA, Zimmermann MB. Serum retinol-binding protein 4 concentration and its ratio to serum retinol Are associated with obesity and metabolic syndrome components in children. J Clin Endocrinol Metab. 2007; 92: 4359-65.
70. •• Goodman E, Graham TE, Dolan LM, Daniels SR, Goodman ER, Kahn BB. The relationship of retinol binding protein 4 to changes in insulin resistance and cardiometabolic risk in overweight black adolescents. J Pediatr. 2009; 154: 67-73. There are only a handful of studies on RBP4 in the pediatric population, mostly cross-sectional. The study by Goodman et al. provided longitudinal data on the role of RBP4 in modulating insulin resistance and suggested that the change in insulin resistance in non-Hispanic black adolescents was related to RBP4 and was dependent on the initial RBP4 level.
71. • Stoppa-Vaucher S, Dirlewanger MA, Meier CA, et al. Inflammatory and prothrombotic states in obese children of European descent. Obesity. 2012; 20: 1662-8. This cros-sectionals study demonstrated the presence of inflammatory and prothrombotic states in obese children as early as 6 years old. They also found that these states were similar in both prepubertal and pubertal obese children.
72. Fritsch P, Kleber M, Rosenkranz A, et al. Haemostatic alterations in overweight children: associations between metabolic syndrome, thrombin generation, and fibrinogen levels. Atherosclerosis. 2010; 212: 650-5.
73. Semeraro F, Giordano P, Faienza MF, Cavallo L, Semeraro N, Colucci M. Evidence that fibrinolytic changes in paediatric obesity translate into a hypofibrinolytic state. Relative contribution of TAFI and PAI-1. Thromb Haemost. 2012; 108: 311-7.
74. • Mauras N, DelGiorno C, Kollman C, et al. Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children. J Clin Endocrinol Metab. 2010; 95: 1060-8. This study exemplifies the presence of risk factros related to inflammation and thrombosis in pre-pubertal children with uncomplicated obesity.
75. •• Lovely RS, Yang Q, Massaro JM, et al. Assessment of genetic determinants of the association of γ′-fibrinogen in relation to cardiovascular disease. Arterioscler Thromb Vasc Biol. 2011; 31: 2345-52. γ′-Fibrinogen is an isoform of fibrinogen that forms more fibrinolysis resistant clots. Very recently γ′-fibrinogen has been implicated in CVD. This study by Lovely et al. reported an independent association between γ′-Fibrinogen CVD.
76. •• Lovely RS, Ramsey JP, Hossain J, George D, Farrell DH, Balagopal P. Gamma' (γ′) fibrinogen and obesity-related cardiometabolic risk factors in children. Obesity. 2011; 19: S170. This represents the first report on γ′-fibrinogen levels in children. The demonstrated a higher concentration of γ′-fibrinogen in obese vs. lean adolescents. The presence of increased levels of γ′-fibrinogen at an early age in the clinical course of obesity is worrying because it the clots formed from γ′-fibrinogen is more fibrinolysis resistant.
77. Balagopal P, George D, Sweeten S, et al. Response of fractional synthesis rate (FSR) of fibrinogen, D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost. 2008; 6: 1296-303.
78. Ferguson MA, Gutin B, Owens S, Barbeau P, Tracy RP, Litaker M. Effects of physical training and its cessation on the hemostatic system of obese children. Am J Clin Nutr. 1999; 69: 1130-4.
79. • Kestila P, Magnussen CG, Viikari JSA, et al. Socioeconomic status, cardiovascular risk factors, and subclinical atherosclerosis in young adults. Arterioscler Thromb Vasc Biol. 2012; 32: 815-21. This study investigated the extent to which socioeconomic status (SES) in young adults is associated with cardiovascular risk factor levels and carotid intima-media thickness (IMT) and their changes over a 6-year follow-up period. This study shows that high education in young adults is associated with favorable cardiovascular risk factor profile and 6-year change of risk factors. Most importantly, the progression of carotid atherosclerosis was slower among individuals with higher educational level.
80. Loucks EB, Pilote L, Lynch JW, et al. Life course socioeconomic position is associated with inflammatory markers: the Framingham offspring study. Soc Scie Med. 2010; 71: 187-95.
81. Nazmi A, Victora C. Socioeconomic and racial/ethnic differentials of C-reactive protein levels: a systematic review of population-based studies. BMC Publ Health. 2007; 7: 212.
82. Howe LD, Galobardes B, Sattar N, et al. Are there socioeconomic inequalities in cardiovascular risk factors in childhood, and are they mediated by adiposity Findings from a prospective cohort study. Int J Obes. 2010; 34: 1149-59.
83. Gimeno D, Ferrie JE, Elovainio M, et al. When do social inequalities in C-reactive protein start? A life course perspective from conception to adulthood in the Cardiovascular Risk in Young Finns Study. Int J Epidemiol. 2008; 37: 290-8.
84. Azad MB, Lissitsyn Y, Miller GE, Becker AB, HayGlass KT, Kozyrskyj AL. Influence of socioeconomic status trajectories on innate immune responsiveness in children. PLoS One. 2012; 7: e38669.
85. Gidding SS, Daniels SR, Kavey RE, for the Expert Panel on Cardiovascular Health and Risk Reduction in Youth. Developing the 2011 integrated pediatric guidelines for cardiovascular risk reduction. Pediatrics. 2012; 129: e1311-9.
86. Hamer M, Sabia S, Batty GD, et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation. 2012.
87. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events. Circulation. 2007; 116: 2110-8.
88. Reinehr T, Roth C, Menke T, Andler W. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab. 2004; 89: 3790-4.
89. Reinehr T, Stoffel-Wagner B, Roth CL, Andler W. High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children. Metabolism. 2005; 54: 1155-61.
90. Balagopal P, George D, Yarandi H, Funanage V, Bayne E. Reversal of obesity-related hypoadiponectinemia by lifestyle intervention: a controlled, randomized study in obese adolescents. J Clin Endocrinol Metab. 2005; 90: 6192-7.
91. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast W. Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Cardiol. 2006; 48: 1865-70.
92. Park TG, Hong HR, Lee J, Kang HS. Lifestyle plus exercise intervention improves metabolic syndrome markers without change in adiponectin in obese girls. Ann Nutr Metab. 2007; 51: 197-203.
93. Kelishadi R, Hashemi M, Mohammadifard N, Asgary S, Khavarian N. Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children. Clin Chem. 2008; 54: 147-53.
94. •• Roth CL, Kratz M, Ralston MM, Reinehr T. Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011; 60: 445-52. This study examined, cross sectional relationships between multiple markers of inflammation and adiposity in 115 obese children and 30 normal-weight controls. Further 62 obese children were followed longitudinally in a 1-year obesity intervention study and these markers were measured simultaneously. Significant correlations between different metabolic risk factors at baseline and after changes of weight status were reported. Weight loss in obese children also reduced various markers of inflammation and insulin resistance. The importance of the study is the simultaneous measurement of a host biomarkers before and after weight loss.
95. • Kamal NN, Ragy MM. The effects of exercise on C-reactive protein, insulin, leptin and some cardiometabolic risk factors in Egyptian children with or without metabolic syndrome. Diabetol Metab Syndr. 2012; 4: 27. The study from Egypt investigated the effect of exercise (3 times/week) for 12 weeks on the levels of CRP, leptin and various traditional risk factors in 49 normal children (control), 32 obese children without metabolic syndrome and 12 obese children with metabolic syndrome. After the intervention, both of the obese groups showed reductions in body weight, BMI and CRP level, but no change in leptin.
96. Barbeau P, Litaker M, Woods KF, et al. Hemostatic and inflammatory markers in obese youths: effects of exercise and adiposity. J Pediatr. 2002; 141: 415-20.
97. Nassis GP, Papantakou K, Skenderi K, et al. Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls. Metabolism. 2005; 54: 1472-9.
98. Gidding SS. Assembling evidence to justify prevention of atherosclerosis beginning in youth. Circulation. 2010; 122: 2493-4.
99. Gallistl S, Sudi KM, Cvirn G, Muntean W, Borkenstein M. Effects of short-term energy restriction and physical training on haemostatic risk factors for coronary heart disease in obese children and adolescents. Int J Obes. 2001; 25: 529-32.
100. Kelly AS, Steinberger J, Olson TP, Dengel DR. In the absence of weight loss, exercise training does not improve adipokines or oxidative stress in overweight children. Metabolism. 2007; 56: 1005-9.
101. • Farpour-Lambert NJ, Aggoun Y, Marchand LM, Martin XE, Herrmann FR, Beghetti M. Physical Activity Reduces Systemic Blood Pressure and Improves Early Markers of Atherosclerosis in Pre-Pubertal Obese Children. J Am Coll Cardiol. 2009; 54: 2396-406. In this 3-month randomized controlled exercise intervention trial 44 pre-pubertal obese children were studied. The intervention reduced BP, arterial stiffness, and abdominal fat and increased cardiorespiratory fitness in the pre-pubertal obese children. However, they did not find any changes in CRP.