Alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may cause a predisposition for disorders and diseases throughout later life. Studies in offspring of diabetic mothers (ODM) have decisively contributed to this perception and our understanding of causal mechanisms. Hormones in particular are environment-dependent organizers of the developing organism. When they are present in non-physiological concentrations during critical periods of early development, they can dose-dependently lead to a permanent malprogramming of fundamental regulatory systems. Worthy of note, fetal and neonatal hyperinsulinism is the pathognomic feature in ODM. Epidemiological, clinical, as well as experimental data obtained by our group during the past two decades indicate that insulin itself, when occurring in elevated concentrations during perinatal life, may program the development of obesity and diabetes. Similarly, this may occur due to general increase of fetal food supply, e.g., in overweight pregnant women and neonatal overfeeding. From a clinical point of view, universal screening and therapy for all types of diabetes during pregnancy as well as avoidance of early postnatal overfeeding, especially by promoting breast feeding, are, therefore, recommended. These measures might serve as causal approaches to a genuine primary prevention.