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Prats-Puig A.,Girona Institute for Biomedical Research | Grau-Cabrera P.,Pediatrics | Riera-Perez E.,Pediatrics | Cortes-Marina R.,Catalonian Institute of Health | And 7 more authors.
International Journal of Obesity | Year: 2013

Objective: Shorter sleep duration predisposes to obesity, but the mechanisms whereby sleep deprivation affects body weight are poorly understood. We tested whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3. Subjects: Body mass index (BMI), waist circumference, visceral fat (abdominal ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297 asymptomatic children (151 boys, 146 girls; age range 5-9 years; BMI s.d. score range-2.0-4.0). Associations between sleep duration and the abovementioned outcomes were tested for three common single-nucleotide polymorphisms (SNPs), namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as for their combination. Results: TT homozygotes (but not A * carriers) for the FTO SNP, exhibited nominal associations between decreasing sleep duration and increasing BMI, waist circumference, visceral fat and HOMA-IR (all P<0.05). Similar associations were observed in children with risk alleles (but not in those without risk alleles) for the TMEM18 and NRXN3 SNPs (P<0.05 to P<0.0001). The three SNPs had additive effects on the negative associations between sleep and, respectively, BMI (P<0.001), waist (P<0.005), visceral fat (P<0.001), HOMA-IR (P=0.010) and SBP (P<0.0005). The combined effects on obesity measures and SBP remained significant after correction for multiple testing. On average, 2 h of sleep less per night was associated with an increase in BMI of 1.0 s.d. (95% confidence interval 0.5-1.6 s.d.) and with 8.0 cm (95% confidence interval 3.6-12.2 cm) more waist circumference in genetically susceptible children. Conclusion: By age 7, common variations in FTO, TMEM18 and NRXN3 influence the vulnerability to metabolic complications of sleep deprivation. Further genetic studies are warranted to replicate these findings in other populations. © 2013 Macmillan Publishers Limited All rights reserved. Source

De Zegher F.,Catholic University of Leuven | Diaz M.,University of Barcelona | Diaz M.,Institute Salud Carlos III | Sebastiani G.,University of Barcelona | And 7 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - Soluble preadipocyte factor 1 (Pref-1) inhibits adipocyte differentiation. We tested whether circulating levels of soluble Pref-1 are higher in smaller fetuses. RESEARCH DESIGN AND METHODS - We performed longitudinal assessments of circulating Pref-1 in infants born appropriate for gestational age (AGA) or small for gestational age (SGA) and also in late-gestational women and in newborns on days 2 and 3. RESULTS - At birth, Pref-1 levels were ~100-fold higher than in adults, being in SGA fetuses ~50% higher than in AGA fetuses. By age 4 months, Pref-1 had reached near-adult levels and the original AGA versus SGA difference had disappeared. Pref-1 levels were low in late-gestational women and were still elevated in newborns. CONCLUSIONS - Pref-1 is abundantly present in the fetus, is higher in SGA than in AGA fetuses, and is likely to be of fetal origin. We speculate that Pref-1 in early life contributes to variation in postnatal adipocyte numbers, in the subsequent expandability of adipose tissue, and thus in the susceptibility to diabetes in later life. © 2012 by the American Diabetes Association. Source

Ibanez L.,University of Barcelona | Ibanez L.,Institute Salud Carlos III | Lopez-Bermejo A.,Girona Institute for Biomedical Research | Diaz M.,University of Barcelona | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). Objective: The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. Design: This was a randomized, open-label study over 7 yr. Setting: The study was conducted at a university hospital. Patients: Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Intervention: Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Main Outcome Measures: Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). Results: None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. Conclusions: In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche. Copyright © 2011 by The Endocrine Society. Source

Ibanez L.,University of Barcelona | Lopez-Bermejo A.,Girona Institute for Biomedical Research | Diaz M.,University of Barcelona | De Zegher F.,Catholic University of Leuven
Fertility and Sterility | Year: 2011

Objective: To study across childhood the features of small for gestational age (SGA) girls with spontaneous catch-up growth. Design: Longitudinal study (age 2-8 years). Setting: University hospital. Patient(s): Post-catch-up SGA girls (n = 18) versus healthy control girls born appropriate for gestational age (AGA; n = 13). Intervention(s): None. Main Outcome Measure(s): Height, weight, fasting glucose, insulin, IGF-I, high-molecular-weight (HMW) adiponectin, LDL and HDL cholesterol, triglycerides, body composition by absorptiometry (2-8 years); visceral fat by magnetic resonance imaging (6-8 years); bone age (by automated reading), sex hormone-binding globulin, DHEAS, and leptin (8 years). Result(s): At age 2 years, AGA and SGA girls were comparable for all study markers. Between 2 and 8 years, girls were prepubertal; AGA and SGA girls gained height, lean mass, and bone mineral content similarly; other outcomes diverged so that, at age 8, SGA girls had markedly higher levels of circulating insulin, IGF-I, DHEAS, LDL cholesterol, and leptin; lower HMW adiponectin and SHBG levels; more total and visceral fat (without being obese); and an older bone age. Conclusion(s): After completing catch-up growth and before starting puberty, SGA girls develop an ensemble that includes not only central adiposity, hyperinsulinemia, and hypoadiponectinemia but also hyperleptinemia, dyslipidemia, lower SHBG and higher DHEAS levels, and faster bone maturation. © 2011 by American Society for Reproductive Medicine. Source

Carrion C.,University of Girona | Aymerich M.,University of Girona | Bailles E.,University Pompeu Fabra | Lopez-Bermejo A.,University of Girona | Lopez-Bermejo A.,Girona Institute for Biomedical Research
Dementia and Geriatric Cognitive Disorders | Year: 2013

Background: The evolution of dementia depends on the underlying pathology, early diagnosis and the availability of effective treatment for some of the symptoms that interfere with the patients' or caregivers' quality of life. Even though there is no specific treatment to reverse dementia, some interventions such as reality orientation and skills training can retard cognitive impairment. Aim: To review existing scientific evidence regarding the efficacy of therapies included in the category of cognition-oriented approaches for people suffering from dementia. Methods: Papers were retrieved from several bibliographic databases (last publication date: 2009) with pre-specified selection criteria, data extraction and methodological quality assessment. Results: Nine reality orientation and 8 skills training trials were identified as meeting the inclusion criteria. Conclusions: Stimulation of cognitive functions, especially by means of reality orientation, improves overall cognitive function in patients suffering from dementia. © 2013 S. Karger AG, Basel. Source

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