Glucose Tolerance, Insulin Sensitivity, and Insulin Secretion in Children Born Small for Gestational Age

Abstract

Intrauterine growth retardation is associated with an increased risk of developing adult diseases, such as noninsulin-dependent diabetes mellitus (NIDDM). NIDDM could result from a decreased insulin sensitivity or a reduced insulin secretion or a combination of both. Glucose tolerance, insulin sensitivity, and insulin secretion were studied in prepubertal children born small for gestational age (SGA). Twenty-nine SGA children with a mean age of 9.1 +/- 1.1 yr and 24 children born appropriate for gestational age (AGA), with a mean age of 9.0 +/- 1.1 yr, were studied. All children were born at term and were prepubertal. Children were studied on two separate days after 12 h of overnight fasting. Day 1: Glucose tolerance was studied with an oral glucose tolerance test. AUC(ins0-120 min)/AUC(gluc0-120 min) was used to estimate beta-cell function in the two groups. Day 2: A hyperinsulinemic euglycemic clamp study was performed to determine insulin sensitivity (M-value). Glucose tolerance and beta-cell function were not different between the two groups. M-value in SGA children was significantly lower than M-value in AGA children: 12.9 +/- 4.0 mg/kg.min vs. 15.6 +/- 2.3 mg/kg.min [P = 0.009; after adjustment for appropriate gestational age body mass index (BMI), P = 0.001]. The M-value tended to be higher in SGA children without catch-up growth compared with SGA children with catch-up growth (15.8 +/- 4.3 vs. 12.3 +/- 3.8 mg/kg.min; P = 0.079) and was comparable to AGA controls (15.6 +/- 2.3 mg/kg.min). The M-value in SGA children who had shown catch-up growth was comparable to AGA children (13.4 +/- 3.4 vs. 15.6 +/- 2.3 mg/kg.min; P = 0.06), provided they had a BMI of 17 kg/m(2) or less. However, the SGA children with catch-up growth and a BMI greater than 17 kg/m(2) were those having the lowest M-values (9.3 +/- 3.4 mg/kg.min). In conclusion, during oral glucose tolerance tests, no differences were found in glucose tolerance and beta-cell function between the SGA and AGA groups. However, the hyperinsulinemic clamp showed a reduced insulin sensitivity in SGA children, which may contribute to the enhanced risk of developing NIDDM in adult life, especially in SGA children with catch-up growth and a high BMI. The implications of our findings in relation to height are unclear, but might be of potential importance when considering GH treatment. In addition, interventions to improve fetal growth and to control obesity in childhood seem to be important factors in the prevention of NIDDM.

Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants

“…Previous studies show that school-aged SGA born children have reduced insulin sensitivity and higher blood pressure than AGA born controls (2,3,6,8,9). Reduced insulin sensitivity in SGA born infants can already be demonstrated in early childhood (5,7).…”

“…This is based on the studies of Barker et al (1), who first indicated the importance of fetal growth for development of the metabolic syndrome in adulthood and showed an increasing prevalence with decreasing birth weight. Not only term smallfor-gestational-age (SGA) born infants, but also preterm born infants have an increased prevalence of several components of the metabolic syndrome, already in childhood (2)(3)(4)(5)(6)(7)(8)(9). The relation between metabolic syndrome components in childhood and fetal growth was studied by Jaddoe et al (10); they showed that first trimester fetal growth restriction is associated with an adverse cardiovascular risk profile at 6 y of age.…”

Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth

“…A recent study shows that insulin sensitivity was not affected in prepubertal children born SGA with subsequent catch-up growth provided that they showed a current BMI within the normal range [25]. Here, we showed that catch-up height has no influence on insulin resistance in subjects born SGA, which is in agreement with studies reporting that insulin resistance is not related to linear growth in children born SGA [25,26]. By contrast, we found a strong effect of catch-up in BMI on insulin resistance in subjects born SGA.…”

Efecto del estado nutricional neonatal en el riesgo de síndrome metabólico en niños obesos de 2 comunas de la Región del Bío-Bío

“…La falta de asociación entre SM y la condición de desnutrición neonatal establecida por las tablas de Juez y Pittaluga/ Alarcón se podría atribuir a que el percentil 10 de IPN no sea el mejor valor de corte para predecir El resultado más sorprendente de nuestro estudio fue la reducción en el riesgo de SM observada en escolares obesos que tuvieron IPN > 90, hallazgo que contrasta con la menor sensibilidad a la insulina descrita para este grupo de RN cuando fueron clasificados en base al peso de nacimiento [27][28][29] . Adicionalmente, las curvas obtenidas al graficar la relación entre el logaritmo del riesgo de SM y el estado nutricional neonatal fueron diferentes si éste fue descrito por IPN o por el peso de nacimiento corregidos por edad gestacional.…”

“…La función que asocia el peso de nacimiento y la glicemia post carga en escolares asume forma de U, teniendo los niños que fueron pequeños y grandes para la edad gestacional menor sensibilidad a la insulina que sus controles normales [27][28][29] . Sin embargo, al evaluar el riesgo de síndrome metabólico infanto-juvenil de acuerdo al estado nutricional neonatal, los resultados han sido contrapuestos 30,31 .…”