RESUMEN
CONTEXT: Short stature homeobox-containing gene (SHOX) variants of unknown clinical significance occur frequently among children with short stature, yet their growth hormone (GH)/insulin-like growth factor-1 (IGF-1) status and response to GH have not been studied. OBJECTIVE: To define GH and IGF-1 status in children with SHOX variants and assess their response to GH. PATIENTS AND METHODS: This is a retrospective review of children with short stature. Children with SHOX variants were compared to those with no variants. Height standard deviation scores (SDS) and IGF-1 SDS at baseline and during GH treatment at 6, 12, and 24 months were analyzed. Growth velocity (GV), maximum GH dose, IGF-BP3, and changes in height SDS, IGF-1 SDS, and GV were compared. RESULTS: Among 355 children, 83 (23%) had SHOX variants. Nineteen different SHOX variants were detected. There was no difference in age, height SDS, IGF-1 SDS, or IGF-BP3 between children with SHOX variants and those with normal SHOX. Height SDS, IGF-1 SDS, IGF-BP3, GV, and GH dose were not different between patients with SHOX variants and those without. CONCLUSIONS: The GH and IGF-1 characteristics of children with short stature were not different between children with SHOX+ variants and children with no variants. Although these findings suggest that SHOX variants are polymorphisms, studies prospectively comparing individual SHOX variants are needed.
Asunto(s)
Estatura/genética , Trastornos del Crecimiento/genética , Proteínas de Homeodominio/genética , Hormona de Crecimiento Humana/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adolescente , Estatura/efectos de los fármacos , Niño , Preescolar , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/farmacología , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Masculino , Estudios Retrospectivos , Proteína de la Caja Homeótica de Baja Estatura , Resultado del TratamientoRESUMEN
OBJECTIVE: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults. DESIGN AND METHODS: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other). RESULTS: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance. CONCLUSIONS: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.