Background/Aims: The metabolic syndrome (MS) is associated with insulin resistance (IR), inappropriate fibrinolysis and high plasma leptin concentrations. The aim of this study was to quantify fibrinolysis and MS-related variables in obese prepubertal children and to evaluate changes in these variables as a result of improved body mass index (BMI), IR and leptin levels following 9 months of treatment. Methods: The homeostasis model assessment for insulin resistance (HOMA-IR), leptin, plasminogen activator inhibitor-1 (PAI-1) and lipid profile were studied at baseline in obese (n = 50) and nonobese children (n = 50), and after 9 months of treatment in obese children. Results: In the cross-sectional study the mean values for insulin, HOMA-IR, triglycerides, leptin and PAI-1 were significantly higher in obese children than in controls. High-density lipoprotein cholesterol (HDLc) and apolipoprotein A-1 were significantly lower. In the longitudinal study, after 9 months, children with lowered BMI standard deviation score displayed a significant decrease in insulin, HOMA-IR, PAI-1, leptin and triglyceride levels, and an increase in HDLc. Only leptin proved to be an independent predictive factor for changes in PAI-1 (p = 0.010). Conclusion: Obesity-linked disorders appear in obese children prior to puberty; these disorders can be improved by decreasing BMI. Changes in leptin levels were found to independently predict changes in PAI-1 in obese children and can help to diagnose complications associated with the obesity.

1.
Olshansky SJ, 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. N Engl J Med 2005;352:1138-1145.
2.
Preston SH: Deadweight? - The influence of obesity on longevity. N Engl J Med 2005;352:1135-1137.
3.
Nathan BM, Moran A: Metabolic complications of obesity in childhood and adolescence: more than just diabetes. Curr Opin Endocrinol Diabetes Obes 2008;15:21-29.
4.
Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
5.
Juhan-Vague I, Alessi MC, Mavri A, Morange PE: Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 2003;1:1575-1579.
6.
Kohler HP, Grant PJ: Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000;342:1792-1801.
7.
Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 2005;365:1415-1428.
8.
Monzavi R, Dreimane D, Geffner ME, Braun S, Conrad B, Klier M, Kaufman FR: Improvement in risk factors for metabolic syndrome and insulin resistance in overweight youth who are treated with lifestyle intervention. Pediatrics 2006;117:1111-1118.
9.
Valle M, Gascón F, Martos R, Ruz FJ, Bermudo F, Morales R, Cañete R: Metabolic cardiovascular syndrome in obese prepubertal children: the role of high fasting insulin levels. Metabolism 2002;51:423-428.
10.
Csabi G, Torok K, Jeges S, Molnar D: Presence of metabolic cardiovascular syndrome in obese children. Eur J Pediatr 2000;159:91-95.
11.
Valle M, Gascón F, Martos R, Ruz FJ, Bermudo F, Ríos R, Cañete R: Infantile obesity - a situation of atherothrombotic risk? Metabolism 2000;49:672-675.
12.
Valle M, Gascón F, Martos R, Bermudo F, Ceballos P, Suanes A: Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children. Int J Obes Relat Metab Disord 2003;27:13-18.
13.
Huang KC, Lin RC, Kormas N, Lee LT, Chen CY, Gill TP, Caterson ID: Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents. Int J Obes Relat Metab Disord 2004;28:470-475.
14.
Singh P, Peterson TE, Barber KR, Kuniyoshi FS, Jensen A, Hoffmann M, Shamsuzzaman AS, Somers VK: Leptin upregulates the expression of plasminogen activator inhibitor-1 in human vascular endothelial cells. Biochem Biophys Res Commun 2010;392:47-52.
15.
Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374.
16.
Dalmau J, Alonso M, Gómez L, Martínez C, Sierra C: Childhood obesity: recommendations of the Nutrition Committee of the Spanish Association of Pediatrics. Part II: diagnosis, comorbidities, treatment (in Spanish). An Pediatr (Barc) 2007;66:294-304.
17.
Reinehr T, Kiess W, Kapellen T, Andler W: Insulin sensitivity in obese children and adolescents according to degree of weight loss. Pediatrics 2004;114:1569-1573.
18.
Reinehr T, Andler W: Changes in the atherogenic risk-factor profile according to degree of weight loss. Arch Dis Chid 2004;89:419-422.
19.
Goran MI, Bergman RN, Avila Q, Watkins M, Ball GD, Shaibi GQ, Weigensberg MJ, Cruz ML: Impaired glucose tolerance and reduced β-cell function in overweight Latino children with a positive family history for type 2 diabetes. J Clin Endocrinol Metab 2004;89:207-212.
20.
Aguilera CM, Gil-Campos M, Cañete R, Gil A: Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome. Clin Sci 2008;114:183-193.
21.
Kang HS, Gutin B, Barbeau P, Owens S, Lemmon CR, Allison J, Litaker MS, Le NA: Physical training improves insulin resistance syndrome markers in obese adolescents. Med Sci Sports Exerc 2002;34:1920-1927.
22.
Kleber M, Schaefer A, Winkel K, Hoffmann D, Wunsch R, Kersting M, Reinehr T: Lifestyle intervention ‘Obeldicks Mini' for obese children aged 4 to 7 years. Klin Padiatr 2009;221:290-294.
23.
Mutch NJ, Wilson HM, Booth NA: Plasminogen activator inhibitor-1 and haemostasis in obesity. Proc Nutr Soc 2001;60:341-347.
24.
Glowinska B, Urban M, Koput A, Galar M: New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents. Atherosclerosis 2003;167:275-286.
25.
Hamdy O, Ledbury S, Mullooly C, Jarema C, Porter S, Ovalle K, Moussa A, Caselli A, Caballero AE, Economides PA, Veves A, Horton ES: Lifestyle modification improves endothelial function in obese subjects with the insulin resistance sydrome. Diabetes Care 2003;26:2119-2125.
26.
Eriksson MA, Rask E, Johnson O, Carlström K, Ahrén B, Eliasson M, Boman K, Söderberg S: Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis. Blood Coagul Fibrinolysis 2008;19:625-632.
27.
Church TS, Finley CE, Earnest CP, Kampert JB, Gibbons LW, Blair SN: Relative associations of fitness and fatness to fibrinogen, white blood cell count, uric acid and metabolic syndrome. Int J Obes Relat Metab Disord 2002;26:805-813.
28.
Sakkinen PA, Wahl P, Cushman M, Lewis MR, Tracy RP: Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000;152:897-907.
29.
Martos R, Valle M, Morales RM, Cañete R, Gascón F, Urbano MM: Changes in body mass index are associated with changes in inflammatory and endothelial dysfunction biomarkers in obese prepubertal children after 9 months of body mass index SD score loss. Metabolism 2009;58:1153-1160.
30.
Yoshinaga M, Sameshima K, Tanaka Y, Wada A, Hashiguchi J, Tahara H, Kono Y: Adipokines and the prediction of the accumulation of cardiovascular risk factors or the presence of metabolic syndrome in elementary school children. Circ J 2008;72:1874-1878.
31.
Nishimura R, Sano H, Matsudaira T, Morimoto A, Miyashita Y, Shirasawa T, Kokaze A, Tajima N: Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study. Cardiovasc Diabetol 2009;8:30.
32.
Beltowski J: Leptin and atherosclerosis. Atherosclerosis 2006;189:47-60.
33.
Thogersen AM, Soderberg S, Jansson JH, Dahlen G, Boman K, Nilsson TK, Lindahl B, Weinehall L, Stenlund H, Lundberg V, Johnson O, Ahren B, Hallmans G: Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction. Eur J Cardiovasc Prev Rehabil 2004;11:33-40.
34.
Morel O, Luca F, Grunebaum L, Jesel L, Meyer N, Desprez D, Robert S, Diagnat-George F, Toti F, Simon C, Goichot B: Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles. Int J Obes (Lond) 2011;35:1479-1486.
35.
Kettaneh A, Heude B, Romon M, Oppert JM, Borys JM, Balkau B, Ducimetière P, Charles MA: High plasma leptin predicts an increase in subcutaneous adiposity in children and adults. Eur J Clin Nutr 2007;61:719-726.
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