The fetal programming hypothesis states that fetal undernutrition during pregnancy results in permanent changes in the offspring's metabolism. A large number of animal studies have evaluated the effect of prenatal undernutrition on later glucose metabolism. Aim: We systematically reviewed the existing animal literature examining effects of prenatal undernutrition on glucose and insulin metabolism. Methods: An electronic search was performed in Medline and Embase to identify all articles that

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... orted studies investigating the effect of prenatal undernutrition on plasma insulin, plasma glucose and beta cell mass in animal models. Summary estimates of the effect of prenatal undernutrition on mean glucose concentration, insulin level, and beta cell mass were obtained through meta-analysis. Results: The search resulted in 1827 articles, of which 117 were potentially eligible, based on title and abstract, and 49 met the selection criteria and were included in the review. Prenatal protein restriction (but not general undernutrition) increased plasma glucose concentrations (0.42 mmol/l (95% CI 0.07 to 0.77)). Both prenatal general undernutrition and protein restriction reduced plasma insulin concentrations (general undernutrition: -0.03 nmol/l (95% CI -0.04 to -0.01), protein restricted: -0.04 nmol/l (95% CI -0.08 to 0.00)) and beta cell mass (general undernutrition: -1.24 mg (95% CI -1.88 to -0.60), protein restriction: -0.99 mg (95% CI -1.67 to -0.31)). In all cases, heterogeneity was significant. Conclusions: Despite significant heterogeneity, evidence from experiments in different species suggests that prenatal undernutrition -both general or protein restriction -results in increased glucose and reduced insulin concentrations as well as beta cell mass in later life.