Changes in serum interleukin-6 concentrations in obese children and adolescents during a weight reduction program.

OBJECTIVE: To investigate the effect of short term energy restriction combined with physical activity on serum concentrations of Interleukin-6 (IL-6) in obese children and adolescents. DESIGN: Longitudinal intervention study of 3.8-5 MJ daily with exercise. SUBJECTS: Forty-nine white obese children and adolescents (31 girls, age 11.9+/-1.8 y; 18 boys, age 11.6+/-1.7 y). MEASUREMENTS: Indexes of obesity, IL-6, leptin, estradiol, systolic and diastolic blood pressure, heart rate at baseline and after 3 weeks. RESULTS: All determined parameters decreased significantly during the 3 week program (IL-6: 3.9+/-4.7 vs 2.0+/-2.2 pg/ml; P<0.05). Body mass index (BMI) fat mass, percentage fat mass (indexes of obesity), and leptin were not related to IL-6 before the program. In contrast, IL-6 concentrations correlated significantly with indexes of obesity and leptin after weight loss. IL-6 concentrations did not correlate with estradiol, systolic and diastolic blood pressure, and heart rate. Changes in IL-6 concentrations correlated significantly with changes in BMI (r=0.25, P<0.05). CONCLUSION: An improved body composition induced by restriction of energy intake and increase in physical activity is associated with more favorable serum concentrations of IL-6 in obese children and adolescents.

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.

The pattern of subcutaneous fat (SAT) is related to metabolic risk factors in obese children. Because weight loss improves the risk-factor profile, we sought to determine whether changes in SAT or SAT-pattern contribute to the improvement in the risk-factor profile after 3 weeks of a low-calorie diet and physical activities. In 22 obese boys (mean age, 11.9 years) and 40 obese girls (mean age, 12 years), fat mass (by means of impedance) and fat distribution (waist and hip circumference) were assessed. The thickness of 15 different subcutaneous adipose tissue layers (SAT-layers) was measured using a Lipometer (Moeller Messtechnik, Graz, Austria). SAT and SAT-pattern (arm-SAT, trunk-SAT, leg-SAT) were calculated. Blood samples were taken for the determination of insulin, glucose, triglycerides, and cholesterol. After 3 weeks, fat mass, waist and hip circumference, SAT, arm-SAT, trunk-SAT (all P <.0001), and leg-SAT (P <.01) were reduced. Besides glucose, metabolic parameters were lowered (all P <.001) but changes in metabolic parameter were interrelated in boys and girls. Age- and sex-adjusted regression revealed that changes in body mass contributed to the variability in changes of insulin (adjusted R(2) =.15, P =.0015). For the change in triglycerides, changes in cholesterol together with subtle alterations in glucose and changes in leg-SAT were found to be the main determinants (adjusted R(2) =.587, P <.0001). The results indicate that the change in the atherogenic and metabolic risk factor profile is largely independent from the concomitant loss in SAT. The reduction in body mass explained only a small part of the variability in changes of insulin, but leg-SAT might participate in the lowering of triglycerides, especially in boys. The contribution of SAT-pattern to the risk factor profile is an issue that needs further investigation.

Determinants of homocysteine during weight reduction in obese children and adolescents.

Plasma homocysteine levels have been shown to be associated with indexes of obesity and insulin resistance in obese children and adolescents. We, therefore, investigated the contribution of changes in body composition, markers of insulin resistance, folate, and vitamin B(12) to changes in homocysteine during a weight reduction program in obese children and adolescents. Thirty-seven obese white girls (mean SD; age, 12 +/- 1.8 years, body mass index [BMI], 26.9 +/- 5.25) and 19 obese white boys (age, 11.9 +/- 1.7 years; BMI, 26.2 +/- 5.2) were investigated for body composition, fasting total plasma homocysteine (tHcy), insulin, C-peptide, folate, and vitamin B(12) before and after a 3-week weight reduction program including physical activities. During weight reduction BMI, fat mass (FM), percentage fat mass, insulin, and C-peptide decreased significantly, whereas homocysteine and vitamin B(12) showed a significant increase. Folate and lean body mass (LBM) remained unchanged. tHcy concentration before weight reduction was a function of age, folate, and C-peptide, whereas tHcy concentration after weight reduction was a function of folate and baseline LBM. Changes in tHcy during weight reduction correlated significantly with baseline LBM and were related inversely to changes in LBM during weight reduction. Children who increased LBM showed lower increases in tHcy compared with children who lost LBM. In multiple linear regression analysis, only baseline LBM contributed independently and significantly to changes in tHcy. Our study suggests that LBM has a significant impact on tHcy metabolism during weight reduction.

Effects of weight loss on leptin, sex hormones, and measures of adiposity in obese children.

Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p < 0.0001), leptin, insulin, and estradiol (all p < 0.0001) but not testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r = 0.54; p < 0.01) and inversely related to the fall in estradiol (r = -0.41; p < 0.05). In girls, changes in testosterone (r = 0.33; p < 0.05) and in estradiol (r = 0.40; p < 0.01) were related to changes in insulin. Stepwise regression showed that initial leptin was the best determinant for the fall in leptin (adjusted R2 = 0.87; p < 0.0001). The results show that alterations in sex hormones are related to changes in certain fat depots in boys whereas in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

Subcutaneous adipose tissue layers as a stable correlate of leptin in response to short term energy restriction in obese girls.

AIMS: We studied the relationship of subcutaneous adipose tissue layers (SAT-layers) measured at 15 specified body sites with leptin before and after a weight loss program for three weeks. SUBJECTS AND METHODS: In 70 obese girls, SAT-layers were measured by means of the optical device, lipometer. Fat mass (FM) was estimated by means of bioelectrical impedance. RESULTS: At the beginning of the study, all estimates of adiposity, insulin, and SAT-layers from the upper body (from 1-neck to 6-lateral chest) were correlated to leptin at a P-value of<0.0001. Percentage FM together with SAT-layer 4-upper back and insulin explained 75% of the variation in leptin (P<0.0001). After three weeks, estimates of adiposity and leptin were reduced (all P<0.0001). Most SAT-layers were reduced, but SAT-layers 8-lower abdomen and 9-lower back were significantly increased. Changes in leptin were best explained by initial leptin, but percentage change (Delta) in insulin, Delta SAT-layer 1-neck, and Delta SAT-layer 3-biceps contributed to the Delta leptin (adj. r(2)=0.47, P<0.0001). In the weight-reduced state, circulating leptin was best explained by three SAT-layers and insulin (adj. r(2)=0.67, P<0.0001). DISCUSSION: The results suggest that Delta changes in leptin are attributable to changes in the endocrine state and subcutaneous fat, and SAT-layers may serve as a stable correlate of leptin in the weight-reduced state.

Effects of short-term energy restriction and physical training on haemostatic risk factors for coronary heart disease in obese children and adolescents.

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+/-1.8 y; body mass index (BMI), 26.9+/-5.25) and 19 obese white boys (age, 11.9+/-1.7 y; BMI, 26.2+/-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 significantly 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 profile in obese children and adolescents.

The influence of weight loss on fibrinolytic and metabolic parameters in obese children and adolescents.

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.

Relationship between plasminogen activator inhibitor-1 antigen, leptin, and fat mass in obese children and adolescents.

Hyperleptinemia may be associated with cardiovascular risk and is linked with parameters of fibrinolytic processes in adults. We studied whether body fatness, leptin, and insulin interact with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children and adolescents. Twenty-three boys (mean +/- SD: age, 10.7 +/- 3.3 years; body mass index [BMI], 28.7 +/- 5.4 Kg/m2) and 19 girls (age, 11.9 +/- 2.7 years; BMI, 29.4 +/- 4.8 Kg/m2) were investigated. Body fat mass (FM) in the children was calculated by bioelectrical impedance analysis, and blood samples were obtained for leptin, insulin, C-peptide, PAI-1-Ag, and tPA-Ag. The children were divided into 3 subgroups according to maturation. Maturity was associated with greater adiposity and higher levels of leptin and C-peptide, but insulin and PAI-1-Ag were not different between prepubertal, pubertal, and late/postpubertal children. PAI-1-Ag was associated with leptin and insulin, but not after adjustment for fatness. PAI-1-Ag was independently associated with tPA-Ag (r = .36, P < .02). Multiple regression analysis showed that tPA-Ag failed to reach the level of significance (P = .07), but FM contributed to the variation in PAI-1-Ag (adjusted R2 = .29). The BMI was the main determinant for the variation in leptin (adjusted R2 = .386) and in insulin (adjusted R2 = .60, all P < .001). Neither gender, maturation, chronological age, or leptin contributed significantly to the variation in either PAI-1-Ag or tPA-Ag. Our data suggest that adiposity and other variables contribute to higher levels of PAI-1-Ag. Leptin seems not to be independently linked with fibrinolytic parameters, but an unfavorable metabolic and fibrinolytic risk profile might emanate from the obese pubertal stage.

The relationship between different subcutaneous adipose tissue layers, fat mass and leptin in obese children and adolescents.

We studied the relationships of subcutaneous adipose tissue layers (SAT-layers), body fat mass (FM) and waist-to-hip ratio (WHR) with leptin in obese children and adolescents. Twenty-nine obese children and adolescents (12 boys: age: 11.3 +/- 3.7 yr; body mass index [BMI]: 28.5 +/- 4) and 17 girls (age: 12.2 +/- 2.2 yr; BMI: 29.8 +/- 4.7) (mean +/- SD) were studied. FM was estimated by bioelectrical impedance. SAT-layers were determined at 15 different body sites from 1-neck to 15-calf by the Lipometer optical device. Leptin and insulin were determined by RIA. Maturity was associated with a greater thickness of certain SAT-layers from the upper body and with a lower thickness of SAT-layers from the abdominal region and lower extremities. Significant correlations were found for all estimates of adiposity and leptin (all p<0.001). Waist and hip circumferences were not correlated to leptin after adjustment for FM. SAT-layers from the upper body were significantly and positively correlated to leptin. Multiple regression analysis revealed FM as a main contributor to the variation in leptin (R2=0.53, p<0.0001). FM together with SAT-layers 5-front chest and 13-rear thigh explained 72% of the variation in leptin (p<0.0001). In a body fat distribution model, hip circumference together with SAT-layers 4-upper back and 2-triceps explained 75% of the variation in leptin (p< 0.0001). The results suggest that SAT-layers and their topography are main determinants for leptin in obese children and adolescents. Maturity in obese children is associated with higher values of upper body SAT-layers and lower values of abdominal and lower extremities SAT-layers. Whether leptin is under the control of certain subcutaneous adipose tissue depots from the upper body remains to be elucidated by longitudinal studies.

No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity.

We studied whether leptin is an independent associate of blood pressure in obese children and adolescence. 102 obese children (48 girls, age: 11.6 +/- 2.22 yr; body mass index [BMI]: 27.45 +/- 4.4; blood pressure: 122.5 +/- 11.1/64.7 +/- 10.6 mm Hg and 54 boys, age: 11.5 +/- 2.4 yr; BMI: 27.6 +/- 4.4; blood pressure: 122.5 +/- 13.2/60.9 +/- 8.1 mm Hg [mean +/- SD]) were investigated. Serum leptin and insulin were measured by RIA; glucose was determined enzymatically. Fat mass (FM) was calculated by bioelectrical impedance. Leptin was higher in girls than in boys (p=0.018) but no significant gender differences were found with respect to indices of adiposity and systolic blood pressure (SBP). Children were divided into three groups, according to pubertal stage (Group 1: prepubertal, 32 boys/13 girls; Group 2: pubertal, 17 boys/25 girls; Group 3: late/postpubertal, 5 boys/10 girls). SBP and DBP correlated with body weight in the whole group (r=0.49, p<0.0001, and r=0.27, p=0.004). In Group 1, BMI showed the highest correlation to SBP; in Group 3 no indices of adiposity were related to SBP. In no case was leptin significantly associated with SBP after adjustment for adiposity. In Group 2, glucose was significantly associated with SBP after adjustment for body weight. In Group 3, however, no correlations were found between SBP, DBP and metabolic characteristics, perhaps due to small sample size. Stepwise multiple regression revealed that body weight and glucose contributed to the variation in SBP in the whole group (R2=0.31, p<0.0001). Insulin accounted for almost 8% of the variation in DBP (R2=0.08, p=0.0034). Body weight contributed significantly to SBP in boys (R2=0.39, p<0.0001) and girls (R2=0.24, p< 0.001). The results imply that body weight contributes independently to the variation in blood pressure. Glucose and insulin contribute to mean blood pressure to some extent, but our data do not support the assumption that leptin per se serves as an independent predictor of blood pressure in obese children and adolescents.

Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents.

OBJECTIVE: To investigate the contribution of serum lipids, parameters of glucose metabolism, body composition and cardiovascular fitness 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 +/- 3.2y; body mass index (BMI), 30.4 +/- 5.3 kg/m2), were screened for haemostatic and metabolic risk factors for CHD. Thirty-five of the participants (18 male, age 13.5 +/- 2.9y; BMI, 29.9 +/-4.5kg/m2; 17 female, age 12.8+/-2.1 y, BMI, 31.1 +/- 5.3 kg/m2) were assessed for cardiovascular fitness by means of incremental cycle ergometer exercise. RESULTS: After adjustment for age, fat mass correlated significantly with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) in boys and girls and factor VIIc only in girls. Children with lower power output (< or = 2.77W/kg) showed significantly higher values for factor VIIc, fibrinogen and tissue-type plasminogen activator antigen (tPA-Ag). Neither body composition nor cardiovascular fitness 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 significant independent proportions of the variance of tPA-Ag. Factor VIIc was explained by C-peptide, insulin and fibrinogen. Von Willebrand factor antigen (vWF-Ag) was significantly 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 fitness.

Inverse correlation between thyroid function and hemostatic markers for coronary heart disease in obese children and adolescents.

BACKGROUND: Childhood obesity may be associated with thyroid dysfunction. Both obesity and hypothyroidism are related to increased risk of coronary heart disease (CHD) in adults through high levels of serum lipids and/or hemostatic abnormalities. OBJECTIVE: To investigate a possible relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents. STUDY DESIGN: Thirty-nine obese children and adolescents were investigated for thyroid function and markers for CHD after overnight fast. Thyroid hormones were measured by radioimmunoassay. Factor VII coagulant activity (VIIc) and factor VIII coagulant activity (VIIIc) were determined using one stage clotting assays; fibrinogen was measured according to the method of Clauss; von Willebrand factor antigen (vWF-Ag), tissue type plasminogen activator antigen (tPA-Ag), and plasminogen activator inhibitor-1 antigen (PAI-1-Ag) were determined by ELISA. RESULTS: We found a significant inverse correlation between fT4 and factor VIIc (r = -0.33, p = 0.03) and fibrinogen (r = -0.35, p = 0.02), which remained significant after adjustment for body fat mass. Factor VIIIc (r = -0.26, p = 0.066) and vWF-Ag (r = -0.28, p = 0.053) tended to be correlated negatively to fT4. fT4 did not correlate with tPA-Ag and PAI-1-Ag. fT3 was inversely related to factor VIIc (r = -0.3, p = 0.039), which was not independent of body fat mass, and showed a less impressive negative correlation with fibrinogen (r = -0.27, p = 0.058). fT3 did not correlate with vWF-Ag, tPA-Ag, or PAI-1-Ag. There was no relationship between TSH and the determined hemostatic markers. CONCLUSION: Our study demonstrates a close relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents and suggests that thyroid dysfunction is associated with an unfavorable hemostatic state even in pediatric patients.

Correlation between cholesterol, soluble P-selectin, and D-dimer in obese children and adolescents.

Thirty-eight obese children and adolescents were investigated for a possible relation between cholesterol and markers of platelet activation, endothelial cell dysfunction, and activation of the coagulation system. Soluble P-selectin, von Willebrand factor antigen (vWf-Ag), D-dimer, and prothrombin fragment 1 + 2 (F1 + 2) were determined by enzyme-linked immunosorbent assays, and factor VIII coagulant activity (VIIIc) was measured by means of one-stage clotting assay. Cholesterol correlated significantly with log P-selectin (r = 0.43, P = 0.003) and log D-dimer (r = 0.33, P = 0.02). Cholesterol did not correlate with vWf-Ag, factor VIIIc, and F1 + 2. Log P-selectin correlated significantly with log D-dimer (r = 0.42, P = 0.003), which remained significant after adjustment for cholesterol (P = 0.02). Log D-dimer correlated significantly with F1 + 2 (r = 0.38, P = 0.01). Our study demonstrates that, in obese children and adolescents, cholesterol is significantly associated with P-selectin and D-dimer, and suggests an unfavorable intercorrelation between metabolic and hemostatic risk factors for coronary heart disease in childhood obesity.

Changes in leptin, insulin and body composition in obese children during a weight reduction program.

BACKGROUND: Girls have higher leptin concentrations than boys at all stages of biological development and this is also seen in the state of obesity. Little is known about whether gender and biological development of obese children influence changes in leptin associated with a short-term weight reduction program. OBJECTIVE: To study whether leptin concentration, body composition and insulin levels in obese children were influenced by a 3-week intervention program including diet and sports. STUDY DESIGN: Sixty-two obese children (32 boys and 30 girls) were examined before and after the intervention program. Body composition was measured by bioelectrical impedance and BMI-SDS was calculated. Serum leptin and serum insulin were determined by RIA. RESULTS: Girls had higher leptin levels than boys, before and after the weight reduction program. Body mass, fat mass (FM), leptin and insulin were decreased after the intervention in both sexes. We found a greater change in serum leptin in girls but the change in FM was of greater magnitude in boys. However, percentage changes in leptin were not significantly different between the sexes. Before the intervention, leptin concentrations were correlated with %FM, FM and moderately with BMI-SDS in all children. Only in pubertal boys did correlation of leptin with %FM increase after the intervention (from r=0.57 to r=0.75, p<0.01). Changes in leptin were found to be associated with initial leptin values in boys (r=0.95, p<0.01) and in girls (r=0.93, p<0.01), independent of Tanner stages. CONCLUSION: Serum leptin levels were positively correlated with adiposity in obese children and a diet and sports intervention program decreased serum leptin, insulin and body fat in all children. Changes in leptin were best described by the initial leptin concentration. The increase in correlation of leptin with %FM in obese pubertal boys after the intervention could have its underlying mechanism in an increased sensitivity to leptin and anabolic hormones.