53 Effects of Intrauterine Growth Restriction (IUGR) and Postnatal Catch-Up Growth on Arterial Blood Pressure (BP), Glucose Tolerance (GT) and Renal Func

Abstract

Introduction: Epidemiological and experimental studies demonstrate that low birth weight is associated with increased risk of arterial hypertension and metabolic diseases in adulthood. Rapid postnatal catch-up growth may constitute an additional risk factor.Aim: To investigate the long term effects of early postnatal overfeeding (OF) after IUGR, on arterial systolic blood pressure (SBP), GT, and renal function in 12 month old, adult rats.Methods: 4 groups of animals were investigated from birth to 12 months: group I, controls: offspring of dams fed normal diet (NP, casein 22 %); group II: offspring of dams fed isocaloric low-protein diet (LP, casein 9 %); group III: postnatal OF (obtained by reduction of litter size); group IV: LP rats exposed to postnatal OF. SBP was measured at 1, 2, 8 and 12 months, glomerular number was determined in newborn pups and renal function (creatinine clearance (CrCl), was assessed at 4 and 12 months. Intraperitoneal glucose tolerance test was performed in 12 months old animals. Data were analyzed by Kruskall-Wallis and Mann-Withney tests.Results: (mean +/- SEM). LP rats offspring had a 20 % birth weight and 38 % glomerular number reduction (p < 0.01). Postnatally OF rats had the higher growth rate during suckling period (p <0.005). Although smaller at birth, LP+OF rats caught up the weight of control offspring within the first postnatal month. Catch-up growth was associated with an elevated SBP from the age of 4 weeks (110 +/-3; 117 +/- 2; 116 +/- 3; 127 +/- 2 mmHg in groups NP, LP, OF, LP+OF rats respectively; p < 0.05), which remained higher in 12 months old LP+OF rats. LP and OF rats displayed a significantly elevated SBP from the age of 2 months in comparison with controls (144 +/- 3; 146 +/-1.6; 130 +/- 3 mmHg, respectively; p < 0.05). But the difference in SBP between LP and controls rats disappeared at the age of 12 months. CrCl decreased with age in LP+OF rats but reached statistical significance in males at 12 months (3.34 +/- 0.2; 4.26 +/-0.3; 4.61+/-1.6; 5.48 +/-1.6 ml/min/kg in LP+OF, LP, OF, controls respectively). At the age of 12 months, fasting glycaemia was significantly elevated in LP+OF rats compared to controls (6.4 vs 5.1 mmol/l). After challenge with a glucose load OF and LP+OF rats had significantly higher 30 min blood glucose levels compared with controls (24+/-1.9; 19+/-1.8; 17 +/-1.2;17+/-0.8 mmol/l in LP+OF, OF, LP, controls respectively; p<0.05).Conclusion: Early catch-up growth in IUGR rats enhances alteration of SBP, glucose tolerance and renal function in adulthood. Long term alteration of renal function seems influenced by gender. Early postnatal overfeeding may amplify single nephron hyperfiltration, and insulin-resistance associated with IUGR, resulting in cardiovascular and metabolic diseases at adulthood.