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Reinehr T.,Witten/Herdecke University | Karges B.,RWTH Aachen | Meissner T.,University Childrens Hospital Dusseldorf | Wiegand S.,Charite - Medical University of Berlin | And 3 more authors.
Journal of Pediatrics | Year: 2016

Objectives To analyze inflammatory markers, adipokines, and hepatokines in obese adolescents with and without type 2 diabetes mellitus (T2DM). Study design We studied high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin-1β, and interferon-γ, the hepatokines (fetuin-A and fibroblast growth factor [FGF]-21), and the adipokines (adiponectin and leptin) in a cross-sectional study of 74 predominately Caucasian adolescents with T2DM aged 12-18 years and in 74 body mass index (BMI)-, age-, and sex-matched controls. Results Adolescents with T2DM had significantly higher concentrations of hsCRP, TNF-α, and interleukin-1β compared with obese controls without T2DM. Interferon-γ was not detectable in obese adolescents with or without T2DM. In multiple linear regression analysis, hsCRP was significantly associated with FGF-21 and BMI, but not with hemoglobin A1c, adiponectin, leptin, fetuin-A, sex, or age. TNF-α was significantly related negatively to leptin, positively to BMI, but not to hemoglobin A1c, adiponectin, fetuin-A, FGF-21 sex, or age in multiple linear regression analysis. Conclusions Increased inflammatory markers are associated with T2DM in adolescents. Because hsCRP was related to FGF-21 and TNF-α was associated with leptin, these findings suggest a link between increased levels of these adipokines and hepatokines and chronic inflammation. Future longitudinal studies in humans are necessary to confirm these hypotheses. © 2016 Elsevier Inc. All rights reserved.

Salgin B.,University of Cambridge | Salgin B.,University Childrens Hospital Dusseldorf | Norris S.A.,University of Witwatersrand | Prentice P.,University of Cambridge | And 7 more authors.
International Journal of Obesity | Year: 2015

Background: Early postnatal rapid 'catch-up' weight gain has been consistently associated with subsequent higher obesity risk and earlier pubertal development. In many low- and middle-income countries, infancy catch-up weight gain is transient and often followed by growth faltering. We explored the hypothesis that even transient catch-up weight gain during infancy is associated with later obesity risk and earlier puberty. Methods: A total of 2352 (1151 male, 1201 female) black South African children in the birth to twenty prospective birth cohort study (Johannesburg-Soweto) underwent serial measurements of body size and composition from birth to 18 years of age. At the age of 18 years, whole-body fat mass and fat-free mass were determined using dual-energy X-ray absorptiometry. Pubertal development was assessed by the research team between ages 9 and 10 years, and it was recorded annually from the age of 11 years using a validated self-assessment protocol. Results: Catch-up weight gain from birth to the age of 1 year, despite being followed by growth faltering between ages 1 and 2 years, was associated with greater mid-upper arm circumference (P = 0.04) and skinfold thickness (P = 0.048) at 8 years of age, and with higher weight (P < 0.001) and body mass index (P = 0.001) at 18 years of age after adjustment for sex, age, smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status. Infancy catch-up weight gain was also associated with younger age at menarche in girls (P < 0.001). This association persisted after adjustment for smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status (P = 0.005). Conclusion: Transient catch-up weight gain from birth to the age of 1 year among children born in a low-income area of South Africa was associated with earlier menarche and greater adiposity in early adulthood. This observation suggests that modifiable determinants of rapid infancy weight gain may be targeted in order to prevent later obesity and consequences of earlier puberty in girls. © 2015 Macmillan Publishers Limited. All rights reserved.

Salgin B.,University of Cambridge | Salgin B.,University Childrens Hospital Dusseldorf | Ong K.K.,University of Cambridge | Ong K.K.,Institute of Metabolic Science | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function. Objective: Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Design: We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity. Results: Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr. Conclusions: Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D. Copyright © 2012 by The Endocrine Society.

Koy A.,University of Cologne | Koy A.,University Childrens Hospital Dusseldorf | Hellmich M.,University of Cologne | Pauls K.A.M.,University of Cologne | And 4 more authors.
Movement Disorders | Year: 2013

Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society.

Klingmann V.,University Childrens Hospital Dusseldorf | Spomer N.,University Childrens Hospital Dusseldorf | Lerch C.,Cochrane Metabolic and Endocrine Disorders Group | Stoltenberg I.,Heinrich Heine University Dusseldorf | And 4 more authors.
Journal of Pediatrics | Year: 2013

Objective To evaluate acceptability of 2 mm solid dosage forms (mini-tablets) as an alternative administration modality in young children in comparison with syrup. Study design Three hundred six pediatric in- and outpatients aged 6 months-5 years (51 in each of 6 age groups) were recruited. An open, randomized cross-over study was conducted to compare acceptability and capability to swallow 2 mm uncoated or coated mini-tablets vs 3 mL syrup. Results In the overall patient population of 306 children, the acceptability of uncoated mini-tablets was superior to syrup (difference in proportions 14.8%, 95% CI 10.2-19.4; P <.0001). In line with this finding, the level of capability to swallow was higher for uncoated mini-tablets compared with syrup as well (difference in proportions 12.3%, 95% CI 5.4-19.3; P =.0008). All 3 pharmaceutical formulations were well tolerated, and none of the 306 children inhaled or coughed because of the syrup or the uncoated mini-tablet; only 2 of the 306 children (both in age group 0.5-1 year) coughed because of the coated mini-tablet, in both cases without clinical relevance. Conclusions Mini-tablets are a valuable alternative to syrup for children 6 months-6 years of age and are more acceptable compared with liquid formulation. Regulatory bodies such as Food and Drug Administration and European Medicine Agency are encouraged to take our data into account for guideline updates and future drug approval processes. © 2013 Mosby Inc. All rights reserved.

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