IUGR in the absence of postnatal "catch-up" growth leads to improved whole body insulin sensitivity in rat offspring

A sub-optimal in utero environment leads to fetal adaptations to ensure short term survival but, in the long-term may lead to disease when the postnatal growth does not reflect that in utero. This study examined the effect of intrauterine growth restriction on whole body insulin sensitivity and metabolic activity in adult rats. Female Wistar-Kyoto rats were fed either a normal protein diet (NPD 20 casein) or a low protein diet (LPD; 8.7 casein) during pregnancy and 2 weeks of lactation. In offspring at 32 weeks of age, indirect calorimetry and dual energy x-ray absorptiometry (DEXA) were performed to assess metabolic activity and body composition. Insulin sensitivity was assessed using a euglycemic-hyperinsulinemic clamp. At 3 days of age, male and female LPD offspring were 23 and 27 smaller than controls, respectively. They remained significantly smaller throughout the experimental period (approximately 10 smaller at 32 weeks). Importantly, there was increased insulin sensitivity in LPD offspring (47 increase in males and 38 increase in females); pancreatic insulin content was normal. Body composition, O2 consumption, respiratory exchange ratio (RER) and locomotor activity were not different to controls. These findings suggest that in the absence of catch-up growth intrauterine growth restriction programs for improved insulin sensitivity.