Obese Children with Low Birth Weight Demonstrate Impaired β-Cell Function during Oral Glucose Tolerance Test

Abstract

Objective:Epidemiological studies have shown an association between birth weight and future risk of type 2 diabetes, with individuals born either small or large for gestational age at increased risk. We sought to investigate the influence of birth weight on the relation between insulin sensitivity and ␤-cell function in obese children. Subjects and Methods:A total of 257 obese/overweight children (mean body mass index-SD score, 2.2 Ϯ 0.3), aged 11.6 Ϯ 2.3 yr were divided into three groups according to birth weight percentile: 44 were small for gestational age (SGA), 161 were appropriate for gestational age (AGA), and 52 were large for gestational age (LGA). Participants underwent a 3-h oral glucose tolerance test with glucose, insulin, and C-peptide measurements. Homeostasis model of assessment for insulin resistance, insulinogenic index, and disposition index were calculated to evaluate insulin sensitivity and ␤-cell function. Glucose and insulin area under the curve (AUC) were also considered. One-way ANOVA was used to compare the three groups.Results: SGA and LGA subjects had higher homeostasis model of assessment for insulin resistance than AGA subjects, but they diverged when oral glucose tolerance test response was considered. Indeed, SGA subjects showed higher glucose AUC and lower insulinogenic and disposition indexes. Insulin AUC was not different between groups, but when singular time points were considered, SGA subjects had lower insulin levels at 30 min and higher insulin levels at 180 min.Conclusions: SGA obese children fail to adequately compensate for their reduced insulin sensitivity, manifesting deficit in early insulin response and reduced disposition index that results in higher glucose AUC. Thus, SGA obese children show adverse metabolic outcomes compared to AGAs andLGAs. (J Clin Endocrinol Metab 94: 4448 -4452, 2009)

Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass

“…First, the fetal period is critical for endocrine pancreatic development in rodents and humans [19]. Second, clinical data show that children and adults with low birth weight demonstrate impaired beta-cell function compared with their normal birth-weight counterparts [20, 21] and human fetuses with severe growth retardation, have a reduction in pancreatic endocrine cell mass [22]. …”

Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

“…We have previously showed that obese children and adolescents born SGA manifest reduced insulin secretion in the context of increased insulin resistance milieu and more evident central repartition of fat than AGA and LGA, with LGA presenting the highest insulinogenic index, despite comparable degree of insulin resistance [17]. Similar to our findings, a study conducted in French obese children has showed a favourable metabolic profile in children born LGA, with obese children and adolescents born with high birth weight displaying approximately 60% higher insulin sensitivity and lower central fat distribution compared with those born eutrophic [9].…”

“…Moreover, as we were interested in the role of fetal factor in the development of metabolic comorbidities [17], low and high birth weights (as defined below) were additional selection factors. Participants were not following a weight-reducing diet, taking any medication, or carrying a previous clinical diagnosis known to influence body composition, glucose metabolism, physical activity, or dietary intake.…”

Birth weight was negatively correlated with plasma ghrelin, insulin resistance, and coenzyme Q10 levels in overweight children

“…This finding is in agreement with previous data reported by Bouhours-Nouet et al [40] who demonstrated that obese children with low birth weight (BW: 2.5 ± 0.4 kg) had higher HOMA-IR and lower muscle insulin sensitivity than those with high birth weight (BW: 4.3 ± 0.4 kg), and high weight gain after 4 years was associated with lower insulin sensitivity, suggesting that low birth weight and no early catch-up weight have been associated with increased risks of insulin resistance from childhood onward and later type 2 diabetes and cardiovascular disease. Brufani et al [41] have also found that SGA obese children showed higher glucose area under curve (AUC) and lower insulinogenic and disposition indexes, suggesting that obese children with low BW resulted in an adverse metabolic outcome compared to obese children with normal and high birth weight.…”