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Prenatal growth restriction and subsequent risks
for type 2 diabetes and cardiovascular risk
Hospital Sant Joan de Déu, Universitat de Barcelona (Barcelona, Spain) Principal investigator Lourdes Ibáñez Associate researcher María Victoria Marcos, Carme Valls
Postdoctoral fellow Marta Díaz, Ana Marina Mosquera PhD student Giorgia Sebastiani
The usefulness of insulin sensitizers as modifiers of Low birth weight and the subsequent postnatal endo- pubertal onset and progression in girls with advanced crine-metabolic abnormalities have become a hot topic, and rapidly progressive puberty and a history of LBW.
mainly due to their link to increased cardiovascular risk The effects of different combinations of insulin sensitiz-and type 2 diabetes in adult life, and the potential for ers and antiandrogens on cardiovascular risk param-detecting early risk markers that allow the implementa- eters in adolescents and young women with ovarian tion of preventive strategies in childhood. Over the last hyperandrogenism, hyperinsulinism and cardiovascular few years, our research line has been centered on the risk.
field of genetic polymorphisms influencing body com-position in the first years of life, inflammation markers, endothelial function, and their relationships with both Areas of expertisebirthweight and the subsequent development of insu- Low birthweight, postnatal catch-up growth and sub- lin resistance, advanced puberty and ovarian hyperan- sequent risks for type 2 diabetes and cardiovascular disease: genetic and environmental influences.
Prepubertal hyperinsulinism and hyperandrogenism and the benefits of early insulin sensitization.
Ovarian hyperandrogenism, hyperinsulinism, abnormal The contribution of both specific genetic polymor- body composition and the benefits of combined insulin phisms and environmental factors in size at birth and in sensitizing and antiandrogen therapy.
body composition in the first two years of life.
The influence of early nutrition on future cardiovascular risks in newborns born small for their gestational age Achievements in 2008(SGA).
A description of the associations among genetic polymorphisms involved in body fat deposition (FTO hyperinsulinism/metabolic syndrome to explore poten-and MCR4 genes), postnatal growth, insulin, body tial associated molecular abnormalities, and the study composition parameters and adipokines up to age 1 of cellular and animal models to increase our under-year in two longitudinal cohorts of, respectively, AGA standing of the pathopysiological mechanisms ac-(appropriate for gestational age) and SGA newborns.
counting for intrauterine growth retardation, postnatal The efficacy of prepubertal insulin sensitization in de- catch-up growth, and associated hyperinsulinism.
laying pubertal onset and menarche; in the develop-ment of insulin resistance and abnormal endocrine-metabolic profile, including excess visceral fat, in girls Publicationsborn SGA; and in prepubertal hyperandrogenaemia Burghardt H, López-Bermejo A, Baumgartner B, Ibáñez and hyperinsulinaemia.
L, Vendrell J, Ricart W, Palacín M, Fernández-Real JM, The efficacy of pioglitazone added to combined metfor- Zorzano A. The nuclear receptor coactivator AIB3 is a min and antiandrogen therapy on cardiovascular risk in modulator of HOMA beta-cell in nondiabetic children. young women with hyperinsulinism and ovarian andro- Clin Endocrinol, 69(5), 730-736 (2008)
Ibáñez L, López-Bermejo A, Callejo J, Torres A, Cabré S, Dunger D, de Zegher F. Polycystic ovaries in non- obese adolescents and young women with ovarian Therapeutic interventions in paediatric entities asso- androgen excess: relation to prenatal growth. J Clin ciated with insulin resistance: the use of new insulin Endocr Metab, 93,196-199 (2008)
sensitizers specifically directed towards the pathophys-
iological mechanisms accounting for abnormalities in Ibáñez L, López-Bermejo A, de Zegher F. Pubertal
body composition, inflammation markers, dyslipidae-
adiposity after fetal growth restraint: towards a calorie- mia, hyperandrogenism, and related disorders of go- restriction-mimetic approach. Metabolism, 57, 672-675
The exploration of new risk markers of hyperinsulinism/metabolic syndrome in patients born SGA.
Ibáñez L, López-Bermejo A, Diaz M, Enríquez G, Metabolomic studies in paediatric patients with Valls C, de Zegher F. Pioglitazone (7.5 mg/d) added to Differences in clinical, endocrine-metabolic variables and regional fat parameters in 6-yr-old children born appropriate (AGA) vs small-for-gestational-age (SGA) matched for height, weight and body mass index [BMI (n=64)]. Results are shown as Z-scores, calculated by dividing the individual values by the corresponding baseline SD in the AGA group. For birthweight (BW) the Z-score was calculated using the corresponding SD in the general population. Plots represent means ± 95% CI. **p ≤ 0.01 and ***p ≤ 0.001 for differences between groups by Student t-test. HMW Adipo: high-molecular-weight adiponectin; Subc Fat: subcutaneous fat; Visc Fat: visceral fat.
flutamide-metformin in women with androgen excess: Research networks and grantsadditional increments of visfatin and high-molecular- Effects on endocrine-metabolic parameters and body weight adiponectin. Clin Endocrinol, 68, 317-320 (2008)
composition of the addition of low-dose pioglitazone to combined metformin+flutamide therapy in young Ibáñez L, López-Bermejo A, Diaz M, Marcos MV, de women with ovarian hyperandrogenism, hyperinsulin-Zegher F. Metformin treatment for 4 yr to reduce to- tal and visceral fat in low-birthweight girls with pre- Instituto de Salud Carlos III. FIS, PI07/90105: cocious pubarche. J Clin Endocr Metab, 93, 1841-
Research directors: Ibáñez L (PI), Casano P, Callejo J, Diaz M, Valls C, del Rio L, Marcos MV, López-Bermejo Ibáñez L, López-Bermejo A, Suárez L, Marcos MV, Diaz A, Enríquez G
M, de Zegher F. Visceral adiposity without overweight in
children born small-for-gestational-age. J Clin Endocr Effect of prenatal growth restraint and putative thrifty
Metab, 93, 2079-2083 (2008)
genes on size at birth and on body composition, and endocrine-metabolic parameters during the first 2 Ibáñez L, Sebastiani G, Diaz M, López-Bermejo A, years of lifeGómez-Roig MD, de Zegher F. Gender specificity of Instituto de Salud Carlos III. FIS, PI05/2405: 2005-2008body adiposity and circulating adiponectin, visfatin, in- Research directors: Ibáñez L (PI), Casano P, Marcos sulin and IGF-I at term birth: relation to prenatal growth. MV, Krauel X, Valls C, del Rio L, Gómez-Roig MD
J Clin Endocr Metab, 93, 2774-2778 (2008)
Diagnostic value of fetal corticosteroids and of the Ibáñez L, Suárez L, López-Bermejo A, Diaz M, Valls adrenal circulation doppler in intrauterine growth C, de Zegher F. Early development of visceral fat ex- cess following spontaneous catch-up growth in chil- Instituto de Salud Carlos III. FIS, PI06/0997: 2006-2008 dren with low birthweight. J Clin Endocr Metab, 93, Research directors: Vela A (PI), Diaz M, Valls C,
925-928 (2008)
Marcos MV, Hernández A, Torres A, Sabrià J, Ferrero S, Marimón A, Mestre M López-Bermejo A, de Zegher F, Díaz-Silva M, Vicente
MP, Valls C, Ibáñez L. Cord serum visfatin at term Influence of early feeding in neurodevelopment and in
birth: maternal smoking unmasks the relation to foetal subsequent cardiovascular risks in infants born small
growth. Clin Endocrinol, 68, 77-81 (2008)
for gestational ageInstituto de Salud Carlos III. FIS, PI08/0443: 2008-2010 López-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Research directors: Ibáñez L (PI), Díaz M, Sebastiani Zegher F, Dunger DB, Ibáñez L. The association be- G, Bosch L, del Rio L, Jiménez R, Hernández, A, tween the FTO gene and fat mass in humans develops Gómez-Roig MD
within two weeks after birth. J Clin Endocr Metab, 93,
1501-1505 (2008)
Endocrine-metabolic and body composition effects of metformin administration in prepubertal children with a López-Bermejo A, Sitjar C, Cabacas A, Vazquez-Ruiz low birthweight for gestational age, postnatal catch-up M, García-González MM, Mora C, Soriano P, Ibáñez growth and risk markers for the metabolic syndromeL. Prenatal programming of renal function: the esti- Instituto de Salud Carlos III. FIS, EC08/00160: mated glomerular filtration rate is influenced by size at 2008-2010
birth in apparently healthy children. Pediatr Res, 64, Research directors: Ibáñez L (PI), Casano P, Diaz M,
97-99 (2008)
Valls C, del Rio L, Marcos MV, Enríquez G, Sebastiani G, Hollenberg G, Fortea E, Cortés R Martin KA, Chang J, Ehrmann DA, Ibáñez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo Influence of early feeding in subsequent cardiovascu-BA. Evaluation and treatment of hirsutism in pre- lar risk in infants born small for gestational age menopausal women: an Endocrine Society Clinical Instituto de Salud Carlos III. FIS, FI06/000425:
Practice Guideline. J Clin Endocr Metab, 93, 2007-2009
1105-1120 (2008)
Research directors: Sebastiani G (PI), Ibáñez L Other funding sourcesOvarian hyperandrogenism and polycystic ovaries in adolescence: influence of birthweight and postnatal body mass indexHospital Sant Joan de Déu, AFR 08/004: 2008-2009Research directors: Conde N (PI), Ibáñez L CollaborationsAll research lines:Francis de Zegher, Department of Woman and Child, Katholieke Universiteit Leuven (Leuven, Belgium)Abel López-Bermejo, Hospital Universitari de Girona Dr Josep Trueta (Girona, Spain)Luís del Río, Centro Médico CETIR (Barcelona, Spain) Usefulness of FABP4 assessment as a prognostic marker in patients with hyperandrogenism, insulin re-sistance, and markers of cardiovascular risk treated with insulin sensitizers and antiandrogens:Lluís Masana, IISPV-Hospital Universitari Sant Joan de Reus (Reus, Spain) and CIBERDEM Metabolomic patterns in patients with hyperandrogen-ism, insulin resistance, and markers of cardiovascular risk treated with insulin sensitizers and antiandrogens:Xavier Correig, Universitat Rovira i Virgili (Tarragona, Spain) and CIBERDEM AwardsResearch Award from the Spanish Society for Paediatric Endocrinology: «Visceral adiposity without overweight in children born smal -for-gestational-age». Madrid, 2008Awardee: Lourdes Ibáñez Research Award from the Spanish Society of Paediatrics: «Molecular and genetic determinants in the development of visceral adiposity and its interaction with prenatal and postnatal growth in prepubertal children». Santiago de Compostela, 2008Awardees: Abel López Bermejo, Lourdes Ibáñez ٩


Pii: s0278-6915(02)00094-7

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