Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age

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(ins0-120min)/AUC(gluc0-120min) was used to estimate P-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 BAIL 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.