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Objective: In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long-term (10 years) effect of GH to SGA-children on IR and safety during treatment. Design: This was a multicenter observational study. Patients: SGA-children who received GH treatment in Spain (stratified by Tanner-stage and age at GH onset [two groups: ≤6 years old or >6 years old]). Measurements: The analysed variables (yearly measures) included auxologic, metabolic (insulin-like growth factor-1 (IGF-1), height velocity [HV], weight and homeostatic model assessment-IR [HOMA-IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005–2007). Results: A total of 389 SGA children (369 Tanner-I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF-1 (standard deviation score [SDS]) and HOMA-IR values tended to increase until the sixth year of GH-treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: −3.0; tenth year: −1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39). Conclusions: HOMA-IR values increased significantly in SGA-children during the first year of GH-treatment, remained stable and were within normal ranges in all cases. Our 10-year data suggests that long-term GH treatment does not promote IR and is well-tolerated, safe and effective. The present work was financed by Merck, S.L.U.

Background. In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance [IR] has been investigated for a short-term period, being necessary a longer observation. Objectives. Evaluate the long-term (10 years) effect of the GH administered to SGA-children on IR and the safety during treatment. Methods. Multicenter observational study in SGA children receiving GH treatment in Spain (stratified by Tanner stage and age at GH onset [two groups: ≤6 years; >6 years]). Analyzed variables (yearly) included auxologic (growth velocity [GV]), metabolic (IGF-1, homeostatic model assessment- IR [HOMA-IR]), and safety ones. Data were collected prospectively since study approval (2007) and retrospectively from GH treatment onset (2005- 2007). Results. Interim analysis (6 years' follow-up) of 389 SGA children (369 Tanner I) from 27 centers. Mean age (SD) at GH treatment onset): 7.2 (3.1) years. IGF-1 (SDS) and HOMA-IR tended to increase until the sixth year with significant differences at the first year, and remaining stable thereafter (within normal ranges). Height (SDS) increased significantly (basal: -3.0; sixth year: -1.5); being the maximum GV at the first year (8.60 cm/year, with higher values in the ≤6 years group). Twenty-one adverse events were reported, two of them serious: type 2 diabetes, and osteonecrosis. Conclusions. The HOMA-IR increased significantly in SGA children during the first year of GH treatment, remaining stable later on, within normal ranges in any case. Our sixth-year data suggest that long-term GH treatment does not promote IR, is well tolerated, safe, and effective Antecedentes. En niños pequeños para su edad gestacional (PEG), se ha investigado la relación entre el tratamiento con hormona de crecimiento (GH) y la resistencia a insulina [RI] a corto plazo, siendo necesario un período mayor. Objetivos. Evaluación del efecto a largo plazo (10 años) de la GH administrada a niños PEG sobre la RI y la seguridad durante el tratamiento. Métodos. Estudio multicéntrico observacional en niños PEG tratados con GH en España, según estadio Tanner y edad al inicio del tratamiento (dos grupos: ≤6 años y >6 años). Las variables analizadas (mediciones anuales) incluyeron parámetros auxológicos (velocidad de crecimiento [VC]), metabólicos (IGF-1, RI [HOMA-IR]) y de seguridad. Datos recogidos prospectivamente, desde aprobación del estudio (2007), y retrospectivamente desde el inicio GH (2005-2007). Resultados. Análisis intermedio (seguimiento a 6 años) de 389 pacientes PEG (369 Tanner I) de 27 centros. Edad media (DE) al inicio GH: 7,2 (3,1) años. IGF-1 (SDS) y HOMA-IR tendieron a aumentar hasta el año 6, con diferencias significativas en el primer año y permaneciendo posteriormente estables (manteniéndose en rangos normales). La talla (SDS) aumentó significativamente (basal: -3,0; año 6: -1,5), con VC máxima en el primer año (8,60 cm/año, mayor en el grupo ≤6 años). Se comunicaron 21 acontecimientos adversos, 2 graves: diabetes mellitus 2 y osteonecrosis. Conclusiones. En niños PEG, el tratamiento con GH aumenta significativamente el índice HOMA-IR en el primer año, permaneciendo posteriormente estable, y siempre dentro de la normalidad. Los datos a 6 años sugieren que este tratamiento a largo plazo no induce RI, es bien tolerado, seguro y efectivo.

Background Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the beta-cell. Given the immunomodulating effects of ghrelin and its trophic effects on beta-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset.Methods BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. beta-cell mass, islet area, islet number, beta-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test.Results Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p

Background. The aim of this study was to investigate the relation between the different bariatric surgeries and pancreatic β-cell turnover. Material and Methods. We used healthy adult male Wistar rats to undergo the different techniques. Three surgical techniques were developed (malabsorptive, Sleeve gastrectomy and Roux-Y Gastric Bypass-), together with two control groups (Sham and fasting control). Pancreatic β-cell mass was measured, as well as apoptosis, proliferation and neogenesis related to cellular turnover. Otherwise, we measured the functional issues to elucidate the physiological role that these surgical techniques trigger in the carbohydrate metabolism (e.g. food intake, weight gain, intraperitoneal glucose tolerance test, and basal glycaemia). Results included the differences in phenotypes of the rat after the surgery. The rats did not show important differences in glycaemic parameters between the surgical groups. The β-cell mass presented modifications related with proliferation processes. A significant increase of β-cell mass in the malabsorptive technique was reported. On the other hand, the peripheral resistance to insulin tended to be reduced in rats which underwent malabsorptive and mixed techniques. Conclusion. This work showed an increase in β-cell mass after the resection of an important portion of small bowel. The Roux-Y Gastric Bypass produced a non-significant increase in β-cell mass. We considered that these implications of surgery over the endocrine pancreas must be one of the mechanisms related to the improvement of type 2 Diabetes mellitus following bariatric surgery.

Los objetivos de este estudio son, realizar una descripción de las características demográficas, antropométricas y de las alteraciones metabólicas de niños atendidos por obesidad resaltando las características aquellos casos de obesidad de inicio temprano (< 10 años) y los de inicio precoz (< 5 años), y evaluar la capacidad diagnóstica de la definición de síndrome metabólico (SM) según diferentes criterios. Métodos: Es un estudio retrospectivo, caso-control, transversal, multicéntrico. Han participado un total de 10 Unidades de Endocrinología Pediátrica de diferentes hospitales españoles con un grupo de 469 niños con obesidad de inicio temprano y otro grupo de 30 niños con obesidad de inicio precoz. El grupo control estuvo constituido por 224 niños sanos menores de 10 años. Se realizó una valoración antropométrica y determinación analítica de parámetros del metabolismo de los hidratos de carbono y lipidograma. Resultados: La presencia de alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil en España es notable, de forma aislada, o englobada bajo la definición de SM. La prevalencia de éste aumenta sustancialmente cuando se considera la resistencia periférica a la acción de la insulina como criterio diagnóstico. Se demuestra cómo en niños menores de 10 años, dichas alteraciones están presentes en un porcentaje reseñable, y se encuentran las primeras alteraciones metabólicas ya en niños obesos < 5 años. Conclusión: En los niños españoles existen alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil de forma aislada o englobada bajo la definición de SM, y ya están presentes a edades precoces. The objectives of this study are to provide a description of the demographic, anthropometric characteristics and metabolic abnormalities in children with early-onset (< 10 years) and of very-early-onset obesity (< 5 years). We also evaluate the diagnostic ability using the definition of metabolic syndrome (MS) according to different criteria. Methods: It is a retrospective, case-control, cross-sectional, multicenter study. A total of 10 Pediatric Endocrinology Units in different Spanish hospitals were involved. A group of 469 children with early-onset obesity and another group of 30 children with very early-onset obesity were studied. The control group consisted of 224 healthy children younger than 10 years. Anthropometric and analytical determination of carbohydrates metabolism parameters and the lipid profile were performed. Results: The presence of metabolic alterations associated with obesity in children and adolescents in Spain is remarkable, either on their own, or encompassed within the definition of MS. This prevalence increases substantially when considering the peripheral resistance to insulin action as a diagnostic criterion. It also shows how children who could not be diagnosed with MS according to the definition provided by the International Diabetes Federation (IDF) due to age below 10 years, these alterations are already present in a remarkable percentage. In fact, metabolic abnormalities are already present in the very-early-onset obese children (