OBJECTIVE: To investigate the contribution of serum lipids, parameters of glucose metabolism, body composition and cardiovascular ®tness to the variance of several haemostatic risk factors for coronary heart disease (CHD) in obese children and adolescents. SUBJECTS AND MEASUREMENTS: Forty-two healthy, obese children and adolescents (20 male, 22 female, age 12.6 AE 3.2 y; body mass index (BMI), 30.4 AE 5.3 kgam 2 ), were screened for haemostatic and metabolic risk factors for CHD. Thirty-®ve of the participants (18 male, age 13.5 AE 2.9 y; BMI, 29.9 AE 4.5 kgam 2 ; 17 female, age 12.8 AE 2.1 y, BMI, 31.1 AE 5.3 kgam 2 ) were assessed for cardiovascular ®tness by means of incremental cycle ergometer exercise. RESULTS: After adjustment for age, fat mass correlated signi®cantly with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) in boys and girls and factor VIIc only in girls. Children with lower power output ( 2.77 Wakg) showed signi®cantly higher values for factor VIIc, ®brinogen and tissue-type plasminogen activator antigen (tPA-Ag). Neither body composition nor cardiovascular ®tness contributed independently to the variance of the determined haemostatic risk factors, except PAI-1-Ag, which has been shown to be determined by fat mass. In multiple linear regression analysis, triglycerides and PAI-1-Ag explained signi®cant independent proportions of the variance of tPA-Ag. Factor VIIc was explained by C-peptide, insulin and ®brinogen. Von Willebrand factor antigen (vWF-Ag) was signi®cantly related to glucose and insulin. CONCLUSION: The results suggest that in obese children and adolescents the haemostatic risk factors factor VIIc, vWF-Ag and tPA-Ag are mainly determinated by plasma insulin and triglyceride concentrations, but are primarily independent of body composition and cardiovascular ®tness.

We studied i) whether short-term weight loss alters plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children, and ii) whether changes in body composition and/or abdominal adiposity are responsible for changes in PAI-1 and tPA-Ag. 20 obese boys (mean age 11.9 yr) and 40 obese girls (mean age 12 yr) were studied before and after three weeks of low-caloric diet and physical activity. Body composition was assessed by means of bioelectrical impedance, and the waist-to-hip ratio (WHR) was measured. Blood samples were determined for insulin, glucose, triglycerides, PAI-1-Ag, tPA-Ag, and the fasting insulin resistance index (FIRI) was calculated. Boys had a greater WHR, higher levels of glucose, and a slightly greater FIRI than girls. Estimates of adiposity, insulin, and triglycerides were correlated with PAI-1 and tPA-Ag. WHR was significantly correlated with fibrinolytic parameters only in girls. Insulin and tPA-Ag contributed to PAI-1 (adj. R2 = 0.36, p <0.0001), whereas percentage fat mass and triglycerides contributed to tPA-Ag (adj. R2 = 0.469, p <0.0001). The weight loss program significantly reduced adiposity, abdominal adiposity, and lowered fibrinolytic and metabolic parameters. Initial levels of PAI-1 and changes in body mass contributed to the fall in PAI-1 (adj. R2 = 0.18, p = 0.0016) and initial levels of tPA-Ag contributed significantly to changes in tPA-Ag (adj. R2 = 0.57, p <0.0001). The results suggest that changes in fibrinolytic parameters are associated with the loss in body mass but can occur independently of a concomitant reduction in fatness. Although initial PAI-1 and tPA-Ag predict the changes of these fibrinolytic parameters, the results do not exclude the possibility that the improvement in metabolic state and changes in unmeasured parameters related to physical activity and low-caloric diet could have influenced our findings.

Recent findings have shown that leptin downregulates the steroid producing system in the adrenal. We studied the interactions of leptin, insulin and cortisol in obese children and adolescents at different stages of maturation. In 44 boys (age 11+/-3.1 yr, body mass index [BMI] 29+/-5.3 [mean +/- SD]) and 35 girls (age 11.4+/-2.6 yr, BMI 29+/-4.3), blood levels of leptin, insulin, cortisol, and glucose were determined. Fat mass (FM) was calculated by bioelectrical impedance. No significant differences were found between boys and girls with respect to humoral and anthropometric characteristics. When children were divided according to maturation stage (prepubertal, pubertal, and late/postpubertal) insulin was higher in the more mature groups (p<0.01) and leptin was higher in the pubertal group (p=0.03). In the prepubertal and pubertal groups, the expected positive relationship between adiposity and leptin was found although the magnitude of this association decreased with maturity. In none of the groups studied was cortisol significantly correlated to leptin. Insulin (p=0.03) and glucose (p=0.01) were positively associated with cortisol in the prepubertal group after adjustment for adiposity. However, in the pubertal group an inverse correlation was found between insulin and cortisol (p=0.03), and between insulin and glucose after control for adiposity. In the late/ postpubertal group, no significant correlations were found between estimates of adiposity and humoral parameters even after adjustment for gender. Stepwise multiple regression failed to detect a significant influence of cortisol to explain the variation in leptin, and vice versa. BMI contributed to the variation in leptin (adj. R2 =0.275, p<0.0001), and glucose added 5% to the variation in cortisol (p=0.03). The results do not confirm the inverse association between leptin and cortisol found in adults. Although BMI reflects levels of leptin, it is likely that several other factors in conjunction with fatness modulate the relationship with leptin. Whether leptin per se exerts an influence on the hypothalamic-adrenal-adipo axis remains to be investigated in longitudinal studies.

OBJECTIVE:To study the changes of haemostatic risk factors for coronary heart disease during a weight reduction programme in obese children and adolescents. DESIGN: A short-term longitudinal study. SUBJECTS: Thirty-seven obese white girls (age, 12 AE 1.8 y; body mass index (BMI), 26.9 AE 5.25) and 19 obese white boys (age, 11.9 AE 1.7 y; BMI, 26.2 AE 5.2). MEASUREMENTS: Fibrinogen, factor VII coagulant activity, von Willebrand factor antigen, and soluble P-selectin were determined before and after a 3 week programme including energy restriction and physical activities. RESULTS: All determined haemostatic risk factors decreased signi®cantly during the programme. Changes in risk factors were correlated to changes in body composition. Children and adolescents with the highest initial concentrations showed the greatest decreases. CONCLUSION: Energy restriction combined with physical activity improves the haemostatic risk pro®le in obese children and adolescents.

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