We review the progress in testing the thrifty phenotype hypothesis. Many @entity1 epidemiological studies both by ourselves and others have confirmed and extended the original observations on which the hypothesis was based. We are not aware of any contradictory findings and we emphasise the strength of the association between birth weight and the subsequent development of the @entity209 . We have worked extensively experimentally to test the hypothesis in a @entity35 model in which pregnant and/or lactating dams are fed a diet moderately restricted in proteins. The range of programming effects that we have discovered in this example of fetal and early postnatal growth restriction is listed and includes changes in hormone receptors, signalling molecules and regulatory enzymes. We have shown the model to develop @entity6 , the @entity209 and signs of @entity177 . We summarise these and other similarities between the phenotype of this model and @entity1 @entity2175 . The number of insults during early development which can lead to a similar outcome is discussed and the suggestion is made that the early life response to stress is limited in its flexibility with outcomes including ageing and decreased longevity. Our preliminary results indicate that some MODY genes could suggest pathways whereby the changes occur and that epigenetic changes during development are involved. We conclude that the way is now clear to discover early @entity1 markers of programming by early life growth restriction and to use these to devise strategies for the prevention of @entity164 2 @entity6 .

For debate: Fetal and early postnatal growth restriction lead to XXXX , the @entity209 and @entity177 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity2175 :: ('MESH:D003924', 'Disease') :: ['Type 2 diabetes and the metabolic syndrome'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic syndrome'] @entity177 :: ('MESH:D051437', 'Disease') :: ['premature renal failure'] @entity164 :: ('MESH:D017827', 'Disease') :: ['Type'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity6 :: (MESH:D003920,Disease) :: ['diabetes']
