Michaela Kleber

Universität Witten/Herdecke, Witten, North Rhine-Westphalia, Germany

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Publications (25)58.14 Total impact

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    ABSTRACT: Objective: The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity. Methods: Serum samples of 80 obese and 40 normal-weight children between 6 and 15 years of age were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Metabolite concentrations and metabolite ratios were compared between obese and normal-weight children as well as between children of different pubertal stages. Results: Metabolite concentration profiles of obese children could be distinguished from those of normal-weight children. After correction for multiple testing, we observed 14 metabolites (glutamine, methionine, proline, nine phospholipids, and two acylcarnitines, p < 3.8 × 10(-4)) and 69 metabolite ratios (p < 6.0 × 10(-6)) to be significantly altered in obese children. The identified metabolite markers are indicative of oxidative stress and of changes in sphingomyelin metabolism, in β-oxidation, and in pathways associated with energy expenditure. In contrast, pubertal stage was not associated with metabolite concentration differences. Conclusion: Our study shows that childhood obesity influences the composition of the serum metabolome. If replicated in larger studies, the altered metabolites might be considered as potential biomarkers in the generation of new hypotheses on the biological mechanisms behind obesity. Copyright © 2012 S. Karger GmbH, Freiburg.
    Obesity Facts 10/2012; 5(5):660-670. · 1.58 Impact Factor
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    ABSTRACT: Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention.
    Obesity 11/2011; 20(2):466-70. · 3.92 Impact Factor
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    ABSTRACT: Adult obese carriers of the A allele of SNP rs324420 in the fatty acid amide hydrolase (FAAH) gene lose more weight and improve associated phenotypes better than non-carriers during an intervention. We aimed to replicate this finding in obese children and adolescents undergoing a one year lifestyle intervention (Obeldicks program). A total of 453 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) were genotyped for rs324420 (C/A) by restriction fragment length polymorphism (RFLP) analysis. Participants were prescribed a balanced diet, containing 55 En% carbohydrates, 30 En% fat, and 15 En% proteins. Moreover, they took part in an exercise therapy once a week. Blood was taken at baseline and after 1 year of intervention. Anthropometric (height, weight, BMI, and BMI-SDS) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA) as well as blood pressure were measured. Both mean BMI and BMI-SDS improved significantly. The mean systolic blood pressure was also lowered and concentrations of HDL-cholesterol increased significantly. However, none of the measured changes were associated with FAAH rs324420 AA/AC genotype. We did not detect evidence for an association of FAAH genotypes with weight reduction in overweight and obese children and adolescents. Hence, the previous finding in adults could not be confirmed. As the length (1 year as compared to 3 months) and mode of treatment (hypocaloric diet in adults vs. physical activity plus balanced meals) of the interventions varied, these parameters might have influenced the inconsistent results.
    Hormone and Metabolic Research 11/2011; 44(1):75-7. · 2.15 Impact Factor
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    ABSTRACT: Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce. Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS. Patients included 59 obese girls with PCOS aged 12-18 yr. Intervention was a 1-yr lifestyle intervention based on nutrition education, exercise training, and behavior therapy. Menses cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG were evaluated. In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of -3.9 kg/m(2)) improved most CRF and decreased their IMT (by a mean of -0.01 cm). Testosterone concentrations decreased (by a mean of -0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (-42%) and oligoamenorrhea (-19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = -0.35; P = 0.048). A linear regression model with changes in IMT as dependent variable demonstrated a significant association with changes in blood pressure and weight status but not with changes in testosterone. Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.
    The Journal of clinical endocrinology and metabolism 08/2011; 96(11):3533-40. · 6.50 Impact Factor
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    ABSTRACT: The outpatient lifestyle interventions Obeldicks (for 8- to 16-year-old obese children; 1-year intervention), Obeldicks Light (for 8- to 16-year-old overweight children; 6-month intervention), and Obeldicks Mini (for 4- to 7-year-old obese children; 1-year intervention) are based on nutrition education, physical activity, behavior therapy, and individual psychological care. Only 17% dropped out of the intervention, and 79% of the more than 1,000 participants reduced their degree of overweight. The mean SDS-BMI reduction was 0.4 (~1.5-2 kg/m(2) BMI reduction) and was associated with a significant improvement of hypertension, dyslipidemia, and disturbed glucose metabolism in the participants compared to an untreated control group. This efficiency was also proven by a multicenter randomized controlled trial. Furthermore, the quality of life of the participants improved significantly. Even 4 years after the end of intervention, the achieved weight loss was sustained. Training manuals and training seminars for professionals assist in the implementation of these lifestyle interventions at further locations.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 05/2011; 54(5):628-35. · 0.72 Impact Factor
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    ABSTRACT: Impaired glucose tolerance (IGT) is a predictor of type 2 diabetes in adults. However, the converting rate from IGT to diabetes is largely unknown in obese children. We analyzed all 128 obese white European children diagnosed with IGT at our institution in the years 2003-2006 (mean age 13.5 ± 2.1 years, 53% female, mean BMI 31.7 ± 6.1 kg/m²) 3.0-5.6 years (mean 3.9 ± 0.6 years) later with an oral glucose tolerance test (oGTT). At follow-up, 20 (16%) children remained in the IGT status, 96 (75%) children converted to normal glucose metabolism, 3 (2%) children developed type 2 diabetes, and 9 (7%) children were lost to follow-up. Comparing the children according to their outcome concerning glucose metabolism at follow-up demonstrated that 2 h glucose levels in oGTT at baseline were significantly (p<0.001) higher in the children remaining IGT and highest in children developing diabetes, while the children did not differ in respect of age, gender, BMI, blood pressure, fasting glucose levels at baseline, or length of follow-up period. Apart from children developing diabetes, who increased their body weight, all the other children did not change their BMI, blood pressure, or fasting glucose levels significantly at follow-up. Obese white children with IGT will likely convert to normal glucose metabolism in the next 3-5 years. Risk factors for developing type 2 diabetes in follow-up were higher 2 h glucose levels in oGTT at baseline and weight gain.
    Experimental and Clinical Endocrinology & Diabetes 03/2011; 119(3):172-6. · 1.56 Impact Factor
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    ABSTRACT: The G-allele of the single nucleotide polymorphism (SNP) rs10830963 in MTNR1B (melatonin receptor 1B gene) is associated with type 2 diabetes mellitus and glucose levels in adults. The aim of this study was to analyze whether there is an allele-dosage effect on glucose metabolism in overweight children and to explore if changes in glucose metabolism in a lifestyle intervention do also depend on genotype. We genotyped rs10830963 in 1118 overweight children and adolescents [mean age 10.7 yr, mean body mass index (BMI) 27.8 kg/m2]; 340 of these individuals completed a 1-yr lifestyle intervention (mean age 10.7 yr, mean BMI 27.9 kg/m2). The degree of overweight [BMI-SDS (standard deviation score)], fasting insulin, glucose, homeostasis model assessment for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were measured before and after intervention. We showed a significant relationship between rs10830963 and basal glucose levels [β:1.101, 95% confidence interval (CI) 0.316-1.886 mg/dL per risk allele; p = 0.006] by linear regression adjusted for age, age(2), and sex. There was no effect of the allele on insulin or indices of insulin resistance or sensitivity. After the 1-yr lifestyle intervention, we observed a significant reduction of BMI-SDS as well as an improvement of HOMA-IR and QUICKI, but no evidence for an association between rs10830963 genotype and changes of glucose levels. The G-allele of rs10830693 in the MTNR1B gene was significantly related to glucose levels, while an impact of this genetic variant on the changes in glucose metabolism in children participating in a lifestyle intervention was not observable.
    Pediatric Diabetes 03/2011; 12(4 Pt 2):435-41. · 2.08 Impact Factor
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    ABSTRACT: Obesity has been shown to be associated with a hypercoagulable state. However, the effect of weight loss on these haemostatic alterations has not been studied yet with an overall function test such as the thrombin generating test (TG) in obese children. We prospectively determined weight status as SDS-BMI, fibrinogen, and performed TG determining time to peak (TTPeak), peak, time preceding the thrombin burst (lag-time), and "endogenous" thrombin potential (ETP) in 27 overweight children (mean age 11.9 ± 2.4 years, 45% female, mean BMI 27.5 ± 5.6 kg/m(2), mean SDS-BMI 2.31 ± 0.48) both at baseline and after 1 year lifestyle intervention based on nutrition education, exercise therapy, and psychological care. Furthermore, thrombin generating test and fibrinogen were determined in 50 healthy children of same age. Overweight children demonstrated significantly higher fibrinogen levels (p = 0.013), shorter lag-time (p < 0.001), and TTPeak (p = 0.028) compared to normal-weight children. ETP (p < 0.001) and peak (p < 0.001) were significantly higher in overweight than in normal-weight children. The overweight children reduced their degree of overweight significantly (-0.4 5 ± 0.22 SDS-BMI; p < 0.001). At the end of the lifestyle intervention, all haemostatic alterations normalized (significant decrease of fibrinogen (p = 0.036), ETP (p = 0.034), and peak (p = 0.001); significant increase of lag-time (p = 0.040) and TTPeak (p < 0.001)). The alterations in the haemostatic system in obese children normalized after weight loss due to lifestyle intervention demonstrating their reversibility.
    Atherosclerosis 02/2011; 216(1):170-3. · 3.71 Impact Factor
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    ABSTRACT: Die ambulanten Schulungen Obeldicks (für acht- bis16-jährige adipöse Kinder; Schulungsdauer ein Jahr), Obeldicks Light (für acht- bis 16-jährige übergewichtige Kinder; Schulungsdauer sechs Monate) und Obeldicks Mini (für vier- bis siebenjährige adipöse Kinder; Schulungsdauer ein Jahr) basieren auf einer Ernährungs-, Verhaltens- und Bewegungstherapie sowie auf individuellen Einzelberatungen. Von den über 1000Teilnehmern reduzierten 79% ihr Übergewicht am Ende der Schulung, nur 17% brachen die Schulung frühzeitig ab. Die mittlere Übergewichtsreduktion lag bei 0,4SDS-BMI (~BMI-Reduktion 1,5–2kg/m2) und verbesserte bei den Teilnehmern – im Vergleich zu einer unbehandelten Kontrollgruppe – den Bluthochdruck, eine Dyslipidämie und Glukosestoffwechselstörungen signifikant. In einer multizentrischen, kontrolliert, randomisierten Studie konnte die Effektivität bestätigt werden. Die Lebensqualität der Teilnehmer verbesserte sich ebenfalls signifikant. Die Übergewichtsreduktion ist nachhaltig, da die erzielten Erfolge auch noch vier Jahre nach Schulungsende nachweisbar sind. Zur Implementierung an anderen Standorten liegen alle Schulungsmaterialien in Form von Trainermanualen vor, und es werden regelmäßig Seminare für Therapeuten angeboten. The outpatient lifestyle interventions Obeldicks (for 8- to 16-year-old obese children; 1-year intervention), Obeldicks Light (for 8- to 16-year-old overweight children; 6-month intervention), and Obeldicks Mini (for 4- to 7-year-old obese children; 1-year intervention) are based on nutrition education, physical activity, behavior therapy, and individual psychological care. Only 17% dropped out of the intervention, and 79% of the more than 1,000 participants reduced their degree of overweight. The mean SDS-BMI reduction was 0.4 (~1.5–2kg/m2 BMI reduction) and was associated with a significant improvement of hypertension, dyslipidemia, and disturbed glucose metabolism in the participants compared to an untreated control group. This efficiency was also proven by a multicenter randomized controlled trial. Furthermore, the quality of life of the participants improved significantly. Even 4years after the end of intervention, the achieved weight loss was sustained. Training manuals and training seminars for professionals assist in the implementation of these lifestyle interventions at further locations. SchlüsselwörterLangfristige Evaluation–Ambulante Adipositasbehandlung–Kardiovaskuläre Risikofaktoren–Kinder–Jugendliche KeywordsTreatment outcome–Outpatient care–Risk factors–Children–Adolescents
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2011; 54(5):628-635. · 0.72 Impact Factor
  • Michaela Kleber, Alexandra Schwarz, Thomas Reinehr
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    ABSTRACT: The relationships between obesity, pubertal development, and height are controversial. Therefore, we compared the prevalence of pubarche, menarche, and voice break between a large collective of obese and normal-weight children and adolescents aged 10-16 years. We assessed weight, height, pubarche, menarche, and voice break in 1383 obese German children and in 6615 children of a representative national German cohort aged 10-16 years. In all obese children, gonadotropins were determined and birth weight data were collected. Independently of gender, the height standard deviation score (SDS) was significantly greater (0.3-1.0) in obese children <14 years compared to the reference cohort. Independently of age, the percentage of obese boys with pubarche was significantly lower compared to age-matched normal-weight boys. In girls <13 years, the prevalence of obese girls with pubarche was significantly lower compared to age-matched normal-weight girls. In boys > or =11 years, the percentage of obese boys with change of voice was significantly lower compared to age-matched normal-weight boys. In girls > or =11 years, the prevalence of obese girls with menarche was significantly lower compared to age-matched normal-weight girls. Birth weight had no impact on pubarche in the obese children. Luteinizing hormone was > 0.3 IU/L in 86% of the children > or =10 years with pubarche. Obese children are taller than normal-weight children up to the age of 14 years. Since obese children demonstrated pubarche, menarche, and voice break later than their normal-weight peers, the increase in height in obese children does not seem to be attributable to earlier onset of puberty.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 24(3-4):125-30. · 0.75 Impact Factor
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    ABSTRACT: Die ambulanten Schulungen Obeldicks (für acht- bis16-jährige adipöse Kinder; Schulungsdauer ein Jahr), Obeldicks Light (für acht- bis 16-jährige übergewichtige Kinder; Schulungsdauer sechs Monate) und Obeldicks Mini (für vier- bis siebenjährige adipöse Kinder; Schulungsdauer ein Jahr) basieren auf einer Ernährungs-, Verhaltens- und Bewegungstherapie sowie auf individuellen Einzelberatungen. Von den über 1000 Teilnehmern reduzierten 79% ihr Übergewicht am Ende der Schulung, nur 17% brachen die Schulung frühzeitig ab. Die mittlere Übergewichtsreduktion lag bei 0,4 SDS-BMI (~BMI-Reduktion 1,5–2 kg/m2) und verbesserte bei den Teilnehmern – im Vergleich zu einer unbehandelten Kontrollgruppe – den Bluthochdruck, eine Dyslipidämie und Glukosestoffwechselstörungen signifikant. In einer multizentrischen, kontrolliert, randomisierten Studie konnte die Effektivität bestätigt werden. Die Lebensqualität der Teilnehmer verbesserte sich ebenfalls signifikant. Die Übergewichtsreduktion ist nachhaltig, da die erzielten Erfolge auch noch vier Jahre nach Schulungsende nachweisbar sind. Zur Implementierung an anderen Standorten liegen alle Schulungsmaterialien in Form von Trainermanualen vor, und es werden regelmäßig Seminare für Therapeuten angeboten.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 01/2011; 54(5). · 0.72 Impact Factor
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    ABSTRACT: Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic syndrome (MetS), which is related to insulin resistance. We examined 51 obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3, IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and HDL-cholesterol concentrations were determined at onset and the end of the one-year lifestyle intervention. In contrast to IGF-I and IGFBP-3, IGFBP-1 correlated significantly to most parameters of the MetS in cross-sectional (waist circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r = -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r = ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of IGFBP-1 was stronger than the associations between changes of leptin or adiponectin, and changes of HOMA. The risk for the MetS was inversely related to IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l) than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese children with fatty liver assessed by ultrasound had significantly lower IGFBP-1 levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ? 4.1 ng/ml). The strong relationships between IGFBP-1, insulin resistance, and the MetS suggest that IGFBP-1 might be a promising marker for these entities in obesity. This study is registered at clinicaltrials.gov (NCT00435734).
    International journal of pediatric obesity: IJPO: an official journal of the International Association for the Study of Obesity 01/2011; 6(3-4):236-43. · 2.00 Impact Factor
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    ABSTRACT: The metabolic syndrome (MetS) is associated with central obesity and leads to increased morbidity and mortality due to cardiovascular disease (CVD). Since obesity is associated with a hypercoagulable state, it has been speculated that hypercoagulation is linking MetS to CVD. We prospectively examined 81 overweight children and 32 normal-weight children aged 10-16 years. We analyzed blood pressure, fasting lipids, glucose, insulin, fibrinogen, and thrombin generating test determining time to peak (TTPeak), peak, time preceding the thrombin burst (lag-time), and 'endogenous' thrombin potential (ETP). Overweight children demonstrated significantly higher fibrinogen levels (p<0.001), shorter lag-time (p<0.001), and TTPeak (p=0.038) compared to normal-weight children. Furthermore, ETP (p<0.001) and peak (p<0.001) were significantly higher in overweight than in normal-weight children. Fibrinogen and all parameters of the clotting test correlated significantly (p always <0.05) to body mass index (BMI) but not significantly to insulin resistance index HOMA-IR or occurrence of MetS in multiple linear backward regression analyses adjusted for age and gender. The increased fibrinogen levels and the changes in the thrombin generation test points towards a haemostatic alteration in overweight children. The parameters of the clotting test were related to the degree of overweight but not to insulin resistance or occurrence of MetS questioning a direct association between MetS and the coagulation system. Longitudinal studies are needed to confirm these findings.
    Atherosclerosis 10/2010; 212(2):650-5. · 3.71 Impact Factor
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    ABSTRACT: To investigate which obese children have an increased risk for impaired glucose tolerance (IGT), a risk factor for later diabetes. We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline. Waist circumference, fasting glucose, lipids, blood pressure, pubertal stage, 2 h glucose in oral glucose tolerance test (oGTT), and HbA1c were determined at baseline and 1 year later. One year after baseline, 19 (11.2%) children demonstrated IGT, 4 (2.4%) children had impaired fasting glucose, no (0%) child suffered from diabetes, and 146 (86%) children still showed normal glucose tolerance. At baseline, the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter, apart from pubertal stage. The children developing IGT entered puberty significantly more frequently (37% vs 3%, P < 0.001). One year after baseline, the children with IGT demonstrated significantly increased waist circumference, blood pressure values, insulin and triglyceride concentrations, and insulin resistance index HOMA. The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes. During the study period of 1 year, more than 10% of the obese children with normal glucose tolerance converted to IGT. Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance, waist circumference, blood pressure, or triglyceride concentrations.
    World journal of diabetes. 09/2010; 1(4):129-34.
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    ABSTRACT: Former small for gestational age (SGA) children are at risk of both obesity and insulin resistance. Longitudinal studies are required to assess a possible relationship between former SGA status and insulin resistance independent of weight status. We hypothesized that obese children with former appropriate for gestational age (AGA) status improve their insulin resistance during weight loss more effectively compared to obese children with former SGA status. A 1-yr longitudinal follow-up study design was adopted in the primary care setting and 341 obese children [8% SGA, mean age 10.5 +/- 0.1 yr, body mass index (BMI) 27.7 +/- 0.2, BMI-standard deviation score (SDS) 2.47 +/- 0.02] were taken for the study. Outpatient 1-yr intervention was based on exercise, behavior and nutrition therapy. We measured insulin resistance index following the Homeostasis model assessment model (HOMA), blood pressure, lipids, glucose, and insulin in all children before and after the 1-yr intervention. In a multiple linear regression analysis adjusted for age, gender, and pubertal stage, changes of HOMA were significantly related to changes of BMI-SDS (-2.55 per loss of 1 BMI-SDS unit; p < 0.001) and SGA status (+2.05 for SGA children; p < 0.001). Changes of BMI-SDS together with gender and age explained 10% of the variance of changes of HOMA, while SGA status explained an additional 4%. After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was not significantly related to any other considered cardiovascular risk factor. Change of weight status predicted change of HOMA in obese children participating in a lifestyle intervention. Changes of HOMA were also predicted by former SGA status supporting that former SGA status influences insulin resistance.
    Pediatric Diabetes 09/2010; 11(6):431-7. · 2.08 Impact Factor
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    ABSTRACT: Impaired glucose tolerance (IGT) is regarded at risk factor for later diabetes. The aim of this study was to identify predictive factors for outcome of IGT in obese children and adolescents. We prospectively examined 79 obese white children and adolescents (mean age 13.1 +/- 2.1 years, 51% female, 76% pubertal) with IGT. Anthropometrics, 2-h glucose in oral glucose tolerance test (OGTT), fasting glucose, insulin, insulin resistance index homeostasis model assessment (HOMA), glycated haemoglobin (HbA(1c)), lipids, blood pressure, waist circumference and pubertal stage were determined at baseline and 1 year later. At follow-up, 32% of the children continued to have IGT, 66% converted to normal glucose metabolism, one child had impaired fasting glucose and one child developed Type 2 diabetes mellitus (T2DM). Children with improvement of IGT had significantly lower weight, waist circumference, triglycerides, 2-h glucose during OGTT and HbA(1c) at baseline compared with children who continued to have IGT. In the children whose glucose tolerance became normal, weight fell, and serum insulin concentrations, HOMA, lipids and blood pressure improved. They were also more likely to enter the late or post-pubertal stage than children who continued to have IGT. Predictive factors for the frequent normalization of IGT in obese children and adolescents were lower weight, HbA(1c) and 2-h glucose levels in OGTT at baseline, as well as a reduction of weight and entering late puberty stages during follow-up. Cardiovascular risk factors and HOMA improved along with the improvement of IGT, supporting an association between IGT, insulin resistance and features of the metabolic syndrome.
    Diabetic Medicine 05/2010; 27(5):516-21. · 3.24 Impact Factor
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    ABSTRACT: Long-term outcome after lifestyle interventions in obese children is largely unknown but important to improving intervention. The aim was to identify predictors of long-term changes in body mass index (BMI) after lifestyle intervention. Annual changes in the BMI SD score (BMI-SDS) over 5 y in 663 obese children (aged 4-16 y) motivated to participate in an outpatient lifestyle intervention were analyzed. Child-specific longitudinal curves based on multilevel growth curve models (MLMs) over 5 y were estimated depending on patient characteristics (age and sex). The mean decrease in BMI-SDS was 0.36 (95% CI: 0.33, 0.39) at the end of the 1-y intervention and 0.46 (95% CI: 0.36, 0.55) 4 y after the intervention. Change in BMI-SDS in the intervention period predicted long-term outcome after 5 y (P < 0.001). MLMs identified age but not sex as a predictor of the outcome: the youngest children (<8 y) at the onset of the intervention had the greatest decrease in BMI-SDS over 5 y, and the oldest children (>13 y) had the least decrease in BMI-SDS (P < 0.05). Whereas there was a larger reduction in BMI-SDS during the intervention in children aged 8-10 y than in children aged 11-12 y, long-term decrease in BMI-SDS was greater in 11-12-y-old children (P < 0.001). Younger age was associated with the best long-term outcome after participation in the lifestyle intervention, which supports the need for early intervention in childhood obesity. Children aged 8-10 y may need modified intervention, because BMI-SDS increased more in the older children in the long term. However, mean BMI-SDS was significantly lower 4 y after the end of the intervention than at baseline in all age groups. This study was registered at clinicaltrials.gov as NCT00435734.
    American Journal of Clinical Nutrition 03/2010; 91(5):1165-71. · 6.50 Impact Factor
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    ABSTRACT: Interventions for obese preschool children are missing in Germany. However, an effective and long-lasting improvement of the health behaviour seems plausible especially in this age, since the health behaviour is impressed in this age span. Therefore, we developed the outpatient one-year lifestyle intervention "Obeldicks Mini" for obese children aged 4 to <8 years and their parents based on nutrition, education, physical activity, and behaviour therapy. This intervention addressed primarily the parents. The training program was evaluated in 84 patients. In the three months before intervention, the degree of overweight significantly increased in the participants (in mean+0.12 SDS-BMI; p=0.002). Based on an intention-to-treat approach, 69% of the participants reduced their overweight, while 24% dropped out of the intervention. The mean SDS-BMI reduction was 0.46 (p<0.001) and was associated with a significant improvement of cardiovascular risk factors such as hypertension, dyslipidemia and insulin resistance. Intima-media thickness as predictive factor for later atherosclerosis decreased significantly. Even 3 years after end of intervention, the achieved weight loss sustained.
    Klinische Pädiatrie 10/2009; 221(5):290-4. · 1.90 Impact Factor
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    ABSTRACT: While an association between androgens and the metabolic syndrome (MS) is well established in obese women, studies concerning this relationship are scarce in obese adolescent girls. Therefore, we analysed the relationships between androgens, MS and intima-media thickness (IMT) in this age-group. In 160 obese girls (aged 12-18 years, mean BMI: 32.6 +/- 5.0 kg/m((2))), androgens [testosterone, dehydroepiandrosterone sulphate (DHEA-S), androstenedione], SHBG and the components of MS (waist circumference, blood pressure (BP), lipids, uric acid, insulin, glucose, 2 h glucose in oral glucose tolerance test (oGTT)) were studied. Furthermore, IMT was determined in a subgroup of 71 randomly chosen girls. Testosterone correlated significantly to systolic BP (r = 0.20), diastolic BP (r = 0.24), 2 h glucose in oGTT (r = 0.30), triglycerides (r = 0.19), uric acid (r = 0.17), waist circumference (r = 0.25) and IMT (r = 0.54). These relationships (except for waist circumference and uric acid) were independent of BMI and insulin resistance index homeostasis model assessment. In contrast to testosterone, DHEA-S, androstenedione and SHBG showed no or weaker correlations to any parameter of MS. The 48 girls with MS demonstrated significantly higher testosterone (1.8 +/- 0.7 nmol/l; P = 0.025) and DHEA-S (4.7 +/- 2.3 micromol/l; P = 0.008) concentrations as compared with the 112 girls without MS (mean testosterone 1.5 +/- 0.7 nmol/l, mean DHEA-S 3.6 +/- 2.3 micromol/l). Testosterone was significantly related to MS and its components in obese adolescent girls independently of BMI and insulin resistance. As IMT was significantly associated with testosterone, this supports the clinical relevance of this finding.
    Clinical Endocrinology 09/2009; 72(6):770-4. · 3.40 Impact Factor

Publication Stats

206 Citations
58.14 Total Impact Points

Institutions

  • 2010–2012
    • Universität Witten/Herdecke
      • • Vestische Kinder- und Jugendklinik Datteln, Universität Witten / Herdecke
      • • Chair of Pediatrics
      Witten, North Rhine-Westphalia, Germany
  • 2011
    • University Hospital Essen
      • Institut für Medizinische Informatik, Biometrie und Epidemiologie
      Duisburg, North Rhine-Westphalia, Germany
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2010–2011
    • Medical University of Graz
      • Clinical Institute of Medical and Chemical Laboratory Diagnostics
      Graz, Styria, Austria