Etude de l'influence du poids de naissance, de la croissance postnatale précoce et de l'indice de masse corporelle actuel sur la répartition de la masse grasse, la sensibilité à l'insuline et les facteurs de risque cardiovasculaire chez 97 enfants obèses

L'obésité infantile et le retard de croissance intra-utérin (RCIU) constituent des facteurs de risque cardiovasculaire à l'âge adulte, pour lesquels l'insulinorésistance joue un rôle physiopathologique central. Le but de l'étude était d'évaluer, chez des enfants obèses, si la croissance fœtale (les coordonnées de naissance) et l'indice de masse corporelle (IMC) mesuré lors de l'évaluation influençaient la répartition corporelle de la masse grasse (MG), l'insulinosensibilité des tissus hépatiques, musculaire et adipeux et l'existence de facteurs de risque cardiovasculaire. Nous avons mesuré la composition corporelle par absorptiométrie de rayons X, calculé à partir d'une hyperglycémie provoquée par voie orale (HGPO) plusieurs index d'insulinosensibilité validés et recherché des facteurs de risque cardiovasculaire chez 97 enfants obèses. L'index d'insulinosensibilité était différent chez les sujets nés RCIU (poids ou taille de naissance 4 kg) : 4.65 +- 2.07 ; 4.35 +- 2.72 et 7.44 +- 3.3 respectivement (p < 0.05). Pour un pourcentage de MG identique, les sujets nés RCIU avaient une répartition tronculaire préférentielle de la MG, comparativement aux sujets nés eutrophiques ou macrosomes (ratio MG androïde/MG gynoïde : 1.19 +- 0.19 ; 1.04 +- 0.28 et 0.91 +- 0.23 respectivement ; p < 0.05). Le RCIU et un IMC actuel élevé favorisaient de manière indépendante l'accumulation tronculaire de la MG et l'insulinorésistance. Ainsi, les enfants obèses ne seraient pas tous égaux face au risque de développer un diabète de type 2 et/ou des maladies cardiovasculaires à l'âge adulte. Outre l'IMC actuel, la prise en compte des coordonnées de naissance, de la croissance pondérale avant 2 ans permettrait, dans la population d'enfants obèses vue en consultation, de mieux identifier les sujets à risque, afin de leur proposer une prise en charge thérapeutique adaptée.PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Laparoscopic adjustable gastric banding in adolescents with severe obesity: Psychological aspects, decision makers of surgery, and 2-year outcomes. A case series

International audienceBACKGROUND: The results of medical treatment of severe obesity in the adolescent population (balanced diet and physical activity) are often unsatisfactory, and bariatric surgery is questioned. The psychological determinants for requesting bariatric surgery in these adolescents are unclear. The objective of this study was to report the psychiatric and psychological aspects as well as the determinants of the medical decision for surgery in a cohort of obese adolescents requesting bariatric surgery by laparoscopic adjustable gastric banding.METHODS: Thirty-five adolescents (12.3-17.7 years of age), were recruited from January 2007 to December 2012. Semistructured interviews were conducted.RESULTS: Fifty-four percent of the adolescents had a psychiatric history and 85% had psychiatric comorbidities. In adolescents undergoing surgery, excess weight loss was 46% after 1 year and 51% after 2years. For patients not receiving surgery, excess weight loss was 0.43% after 1 year (P=0.001). Compliance with medical treatment was the only significant element contributing to the decision to perform surgery. Results in terms of satisfaction and perception 1 and 2years after surgery were encouraging.CONCLUSION: Bariatric surgery is feasible in young patients and produces good results in terms of excess weight loss. We argue that compliance with medical treatment is probably one of the most important elements for making the decision to perform bariatric surgery and in excess weight loss after surgery. We probably need to focus on the compliance of young patients and evaluate how this can be improved

Novel compound heterozygous Thyroglobulin mutations c.745+1G>A/c.7036+2T>A associated with congenital goiter and hypothyroidism in a Vietnamese family. Identification of a new cryptic 5′ splice site in the exon 6

Several patients were identified with dyshormonogenesis caused by mutations in the thyroglobulin (TG) gene. These defects are inherited in an autosomal recessive manner and affected individuals are either homozygous or compound heterozygous for the mutations. The aim of the present study was to identify new TG mutations in a patient of Vietnamese origin affected by congenital hypothyroidism, goiter and low levels of serum TG. DNA sequencing identified the presence of compound heterozygous mutations in the TG gene: the maternal mutation consists of a novel c.745+1G>A (g.IVS6 + 1G>A), whereas the hypothetical paternal mutation consists of a novel c.7036+2T>A (g.IVS40 + 2T>A). The father was not available for segregation analysis. Ex-vivo splicing assays and subsequent RT-PCR analyses were performed on mRNA isolated from the eukaryotic-cells transfected with normal and mutant expression vectors. Minigene analysis of the c.745+1G>A mutant showed that the exon 6 is skipped during pre-mRNA splicing or partially included by use of a cryptic 5′ splice site located to 55 nucleotides upstream of the authentic exon 6/intron 6 junction site. The functional analysis of c.7036+2T>A mutation showed a complete skipping of exon 40. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool NNSplice, Fsplice, SPL, SPLM and MaxEntScan programs were investigated and evaluated in relation with the experimental evidence. These analyses predicted that both mutant alleles would result in the abolition of the authentic splice donor sites. The c.745+1G>A mutation originates two putative truncated proteins of 200 and 1142 amino acids, whereas c.7036+2T>A mutation results in a putative truncated protein of 2277 amino acids. In conclusion, we show that the c.745+1G>A mutation promotes the activation of a new cryptic donor splice site in the exon 6 of the TG gene. The functional consequences of these mutations could be structural changes in the protein molecule that alter the biosynthesis of thyroid hormones.Fil: Citterio, Cintia Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Morales, Cecilia Mariel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Bouhours Nouet, Natacha. Centre Hospitalier Universitaire d'Angers; FranciaFil: Machiavelli, Gloria Angelica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Bueno, Elena. Universidad de Salamanca; EspañaFil: Gatelais, Frédérique. Centre Hospitalier Universitaire d'Angers; FranciaFil: Coutant, Regis. Centre Hospitalier Universitaire d'Angers; FranciaFil: González Sarmiento, Rogelio. Universidad de Salamanca; EspañaFil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Salamanca; EspañaFil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Salamanca; Españ

Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor &beta; gene (THRB) and exon 7 of the albumin gene (ALB). We found 56 THRB variants (i.e., 38% of the 303 index cases, called RTH&beta; group). Among the samples screened for FDH variants, 18% had the variant R218H in ALB (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTH&beta; group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTH&beta; patients. Clinically, patients with FDH had fewer symptoms than patients with RTH&beta;. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay

Lower Circulating Sertoli and Leydig Cell Hormone Levels During Puberty in Obese Boys: A Cross-sectional Study

International audienceAbstract Context Alterations in semen characteristics and circulating Sertoli and Leydig cell hormones have been described in obese male adults. Whether hormonal alterations occur before adulthood has not been fully evaluated. Objective We describe circulating Sertoli and Leydig cell hormone levels in overweight–obese (ow/ob) boys through childhood and adolescence in a cross-sectional study. Methods Monocentric study in the Pediatric Endocrinology Unit of Angers University Hospital. Three hundred and fifty-one obese and overweight boys aged 5-19 years underwent physical examination, dual-energy X-ray absorptiometry for body composition, oral glucose tolerance test on insulin and glucose, and measurements of follicle-stimulating hormone, luteinizing hormone, anti-Müllerian hormone (AMH), inhibin B, testosterone, and estradiol. Hormonal levels were compared with normative data obtained from 652 healthy nonoverweight nonobese boys of similar age or Tanner stage. Results Median inhibin B and testosterone levels during puberty were significantly lower in ow/ob than in healthy boys (1) from age &gt;12 years and thereafter for inhibin B, and (2) from age &gt;14 years and thereafter for testosterone. At Tanner stages 4 and 5, 26%, 31%, and 18% of inhibin B, testosterone, and AMH values were below the 5th percentile in ow/ob subjects (P &lt; .01). In multiple regression analyses, estradiol and total bone mineral density Z-score were negative predictors of inhibin B, fat mass percentage was a negative predictor of testosterone, and insulin was a negative predictor of AMH. Conclusion Lower Sertoli and Leydig cell hormone levels during puberty were observed in the ow/ob boys

Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism

International audienceAbstract Context Resistance to thyroid hormone β syndrome (RTHβ) is caused by pathogenic variants in the THRB gene, but such variants are found in only 85% of cases. We report the case of a patient with RTHβ phenotype but for whom we found a pathogenic variant of the THRB gene in a mosaic state. Case Description The patient is a 52-year-old woman with clinical and biological signs of RTHβ. Symptoms included asthenia, cardiac palpitations, and diarrhea. Repeated thyroid function tests showed an elevated serum TSH, elevated serum free T4, and variably normal or slightly elevated serum fT3. Pituitary magnetic resonance imaging was normal, and the thyrotropin-releasing hormone test result was compatible with the diagnosis of RTHβ syndrome. Initial Sanger sequencing on blood samples could not highlight the presence of a mosaic variant because of insufficient sensitivity. When next-generation sequencing became accessible, blood samples were retested and we found a known pathogenic variant: c.949G &gt; A; p.(ala317Thr), with an allelic frequency of 12%. Other samples from tissues of different embryological origin were also tested and found an allelic frequency of 5.7%, 17.9%, 9.9%, 6.4%, and 0% on urine tests, oral swab, nasal mucosa swab, skin biopsy, and conjunctival swab, respectively. Cloning confirmed the allelic frequency observed. Conclusions We highlight that a pathogenic variant in a mosaic state in the THRB gene may be the cause of an authentic RTHβ syndrome. High-throughput sequencing of multiple tissues eases the detection of pathogenic variant in a mosaic state and allows the correct diagnosis of patients with true RTHβ, thus avoiding patient mismanagement

Outcomes of hybrid closed‐loop insulin delivery activated 24/7 versus evening and night in free‐living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial

International audienceAims: To assess the safety and efficacy of hybrid closed-loop (HCL) insulin delivery 24/7 vs. only evening and night (E/N), and on extended 24/7 use, in free-living children with T1D.Materials and methods: Pre-pubertal children (n = 122; 49F/73M, age: 8.6 ± 1.6, diabetes duration: 5.2 ± 2.3 years, insulin pump use: 4.6 ± 2.5 years, HbA1c: 7.7 ± 0.7%/61 ± 5 mmol/mol) from 4 centers were randomized for 24/7 vs. E/N activation of the Tandem Control-IQ system for 18 weeks. Afterwards, all children used the activated system 24/7 for 18 more weeks. Primary outcome was %time spent in 70-180 mg/dL glucose range (TIR).Results: HCL was active 94.1% and 51.1% of time on 24/7 and E/N modes, respectively. TIR from baseline increased more on 24/7 vs. E/N: 52.9 ± 9.5 to 67.3 ± 5.6 (+14.4%, 95CI: 12.4-16.7%) vs. 55.1 ± 10.8 to 64.7 ± 7.0 (+9.6%, 95CI: 7.4-11.6%), p = 0.001. Mean %time below range was similarly reduced from 4.2 and 4.6 to 2.7, and mean %time above range more on 24/7 mode: 41.9 to 30.0 (-11.9%, 95CI: 9.7-14.6%) vs. 39.8 to 32.6 (-7.2%, 95CI: 5.0-9.9%), p = 0.007. TIR increased through the whole range of baseline levels and always more with 24/7 use. The results were maintained during extension phase in those initially on 24/7 use and improved in those with initial E/N use up to those with 24/7 use. Neither ketoacidosis nor severe hypoglycemia occurred.Conclusions: Our study demonstrates the safety and efficacy of Tandem Control-IQ system in free-living children with T1D for both E/N and 24/7 use. 24/7 use shows better outcomes, sustained for up to 36 weeks with no safety issue. This article is protected by copyright. All rights reserved