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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.