THEN AND NOW The thrifty phenotype hypothesis revisited

their co-workers published some of their pioneering papers proposing the ‘thrifty phenotype hypothesis ’ in Diabetologia (4;35:595–601 and 3;36:62–67). Their postulate that fetal programming could represent an important player in the origin of type 2 diabetes, the metabolic syndrome and cardiovascular disease (CVD) was met with great scepticism. More recently, their observations have been confirmed and expanded in many epidemiological and animal experi-mental studies, and human integrative physiological studies have provided insights into some of the underlying molec-ular mechanisms. Type 2 diabetes is a multiple-organ dis-ease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 dia-betes and the metabolic syndrome. Only two among the 45 known type 2 diabetes susceptibility genes are associated with low birthweight, indicating that the association be-tween low birthweight and type 2 diabetes is mainly non-genetic. Prevention programmes targeting adult lifestyle fac-tors seems unable to stop the global propagation of type 2 diabetes, and intensive glucose control is inadequate to reduce the excess CVD mortality in type 2 diabetic patients. Today, the thrifty phenotype hypothesis has been established as a promising conceptual framework for a more sustainable inter-generational prevention of type 2 diabetes