Gudrun Weinhandl

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.

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±3.2 y; 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±2.9 y; BMI, 29.9±4.5 kg/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 (≤ 2.77 W/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.

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.

Do children and adolescents with type 1 diabetes mellitus have a higher frequency of parietal cell antibodies than healthy controls

Objectives:Parietal cell antibodies (PCA) are markers of autoimmune gastritis (AG). AG can lead to hypergastrinemia and iron-deficiency anaemia (IDA). Compared to healthy controls, adults with type 1 diabetes mellitus (T1DM) show a higher prevalence of PCA (1% vs 20%). The aim of the present study was to evaluate the frequency of PCA in children and adolescents with T1DM compared to healthy controls and the clinical and biochemical markers. Patients and Methods:We studied 170 patients (87 boys) with T1DM (mean age 12.9 years) and 101 healthy controls (49 boys; mean age 13.0 years). PCA, free T4, free T3, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured in all of the patients. In addition, gastrin, pepsinogen I, iron, ferritin, vitamin B12, and folate were measured in patients with T1DM only. Gastroscopy was carried out in patients with T1DM having high (>100 U/mL) PCA levels. Results:The frequency of PCA in patients with T1DM was 5.29% compared to 1.98% in healthy controls (not significant). PCA was strongly correlated to both thyroid peroxidase antibodies (TPOAb) and gastrin levels (P = 0.001). IDA was present in 4 of 9 patients from the PCA-positive group compared to 4 of 160 patients from the PCA-negative group. Hypergastrinemia was found in 2 PCA-positive patients. Histopathologically, 1 of 4 patients showed early symptoms of AG. Conclusions:Children and adolescents with T1DM have a lower frequency of PCA than is reported for adults. Compared to healthy controls, they seem to be at increased risk for developing PCA, in particular if positive for TPOAb, but overt clinical disease is rare in children with T1DM.

Ghrelin - an indicator for fat oxidation in obese children and adolescents during a weight reduction program.

The aim of this study was to investigate the effect of short-term energy restriction combined with physical activity on changes in substrate oxidation and changes in plasma concentrations of ghrelin. We designed a longitudinal intervention study of 4.2 MJ (= 1,000 kcal) daily with exercise. Eighteen obese children and adolescents (age: 13.1 +/- 1.6 years, 13 girls, 5 boys, 17 White, 1 Black) participated. We measured body mass index (BMI), plasma ghrelin, resting energy expenditure (REE), VCO2, VO2 and respiratory quotient (RQ) at baseline and after 10 days. There was a significant decrease of BMI during the 10 day program (28.6 +/- 4.3 vs 27.5 +/- 4.2; p < 0.001). Ghrelin and RQ showed a tendency to increase, but the difference did not reach significance (ghrelin: 83.4 +/- 37.1 vs 99.5 +/- 41.2, p = 0067; RQ: 0.83 +/- 0.06 vs 0.85 +/- 0.08, p = 0.433). The changes in RQ were significantly and independently correlated with the changes in plasma ghrelin (p = 0.029). The increase in RQ suggests a shift from fat oxidation towards carbohydrate oxidation. Ghrelin reflects the same sensitivity as RQ to changes in energy balance. Therefore, ghrelin seems to be a sensitive indicator for changes in substrate oxidation.

No relationship between leptin and cortisol in obese children and adolescents.

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.

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 (Δ) in insulin, Δ SAT-layer 1–neck, and Δ SAT-layer 3–biceps contributed to the Δ leptin (adj. r2=0.47, P<0.0001). In the weight-reduced state, circulating leptin was best explained by three SAT-layers and insulin (adj. r2=0.67, P<0.0001).DISCUSSION: The results suggest that Δ 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.

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.

Ghrelin does not regulate the GH response to insulin‐induced hypoglycaemia in children but could be involved in the regulation of cortisol secretion

Objective  Ghrelin activates the growth hormone secretagogue receptor GHS‐R. It strongly stimulates GH secretion and has a role in energy homeostasis. The relationship between plasma ghrelin and cortisol levels during insulin‐induced hypoglycaemia in prepubertal and pubertal children has not yet been investigated. The aim of the present study was to establish whether insulin‐induced hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin concentrations are related to changes in GH and cortisol in children.

Diagnosis and prevalence of Congenital Adrenal Hyperplasia (CAH) in Austrian children screened or not screened for CAH

Prevalence of Congenital Adrenal Hyperplasia (CAH) is not exactly known in the Austria; a number of patients with CAH might not be diagnosed, especially males. CAH is in about 95 % of the cases due to a defect in the 21-hydroxylation (‘classical CAH’). Newborn screening for CAH, based on the measurement of 17α-hydroxyprogesterone (17-OHP) was shown to be efficient for diagnosis, and is part of the newborn screening programme in Austria since April 2001. In our study we compared 2 groups of children: Group A, children born in Styria (a province of Austria), 1992 – 2001, n = 119.001, m 61.256, and f 57.745; Group B, children born in Styria 2002 – 2011, n = 103.228, m 52.722, and f 50.506 In group A (patients not screened), CAH was diagnosed in 8 children (m 4; f 4); 4 of them with simple virilising (SV) 21-OH deficiency (m 3; f 1) and 4 with salt wasting (SV) 21-OH deficiency (m 1; f 3). In group B, 98,7 % of all newborns born in Styria could be screened by measuring 17-OHP in a dried blood spot on filter paper. Recall rate was 0,578 %. CAH was diagnosed in 10 children (m 3: f 7). 8 of them with SW (m 2; f 6), and 2 with 11β-hydroxylase deficiency (m 1; f 1). Whereas group A displayed the expected Mendelian sex ratio, group B showed a strong female predominance (m 3; f 7) Prevalence of CAH was 1:14.875 newborns in group A (not screened). In group B (newborns screened) prevalence was 1:10.132. If one exclude the 2 patients with 11s-hydroxylase deficiency from group B, prevalence of ‘classical CAH’ was 1:14.875 in group A, compared to 1:12.903 in group B. These data show that newborn screening for CAH seems to increase the rate of detection of CAH.