OBJECTIVE: The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction. RESEARCH DESIGN AND METHODS: Serum levels of adiponectin, leptin, fasting glucose, fasting insulin (I(F)), the homeostasis model assessment insulin resistance index (HOMA-IR), IGF-1, free IGF-1, IGF-binding protein (IGFBP)-1 and -3, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaluated in 57 children at age 4-10 years. Of these, 32 had been born appropriate size for gestational age (AGA) and 25 SGA (14 in the <3rd percentile and 11 in the 3rd-10th percentile). RESULTS; The SGA 3rd-10th percentile children were already insulin resistant at prepubertal age (I(F) 39.6 +/- 16.8 vs. 27 +/- 12 pmol/l, P < 0.01, and HOMA-IR 1.4 +/- 0.6 vs. 0.95 +/- 0.42 in SGA vs. AGA children, P < 0.05). Their IGF-1 and IGFBP-3 concentrations were significantly lower than those in AGA children (160.4 +/- 66.2 vs. 207 +/- 66.8 microg/l, P < 0.05 and 2.3 +/- 0.4 vs. 3.51 +/- 1.21 mg/l in SGA vs. AGA children, P < 0.01). The SGA <3rd percentile children had higher adiponectin (15.6 +/- 5.7 mg/l, P < 0.05) and IGFBP-1 levels (113.5 +/- 33.9 microg/l, P < 0.05) than AGA children (11.3 +/- 6.6 mg/l and 90.8 +/- 24.2 microg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 +/- 68.4 microg/l, P < 0.05 and 2.4 +/- 0.7 mg/l, P < 0.01). They also had significantly lower waist circumference (P < 0.05). Leptin levels did not differ among groups, but an inverse correlation with IGFBP-1 (r = -0.55, P < 0.01) was found in the pooled SGA group. CONCLUSIONS: Intrauterine growth restriction appears to affect the IGF axis at prepubertal age, and its severity plays a role in insulin sensitivity.