The diabetic pregnancy, macrosomia, and perinatal nutritional programming.

Health and diseases are generally perceived to be caused genetically. It is meanwhile accepted, however, that alterations in the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may also predispose to disorders and diseases throughout later life. Studies in the offspring of diabetic mothers (ODM) have decisively contributed to this perception and our understanding of causal mechanisms. It has long been known that hormones are environment-dependent organizers of the developing neuroendocrine-immune network, which regulates all fundamental processes of life. When present in non-physiological concentrations during critical periods of development, induced by altered intrauterine and/or neonatal environment, hormones can therefore also act as endogenous functional teratogens. Fetal and neonatal hyperinsulinism is the pathognomic feature in ODM. Epidemiological, clinical, as well as experimental data obtained by our group indicate that insulin itself, when occurring in elevated concentrations during perinatal life, may program the development of obesity and diabetes. Similar situations may occur due to maternal overweight accompanied by increased fetal food supply, and neonatal overfeeding. From a clinical point of view, general screening and therapy of all types of diabetes during pregnancy as well as avoidance of early postnatal overfeeding are therefore recommended. These measures might serve as causal approaches to a genuine primary prevention.