HYPOXIA-INDUCED SYMPATHETIC INHIBITION OF THE FETAL PLASMA-INSULIN RESPONSE TO HYPERGLYCEMIA

Large-for-delivery date babies, considered characteristic of diabetic pregnancy, are believed to result from fetal hyperinsulinemia. Paradox ically, infant birth weights tend to be low-for-delivery date in mothe rs with more severe diabetes. We tested the hypothesis that hypoxemia in such fetuses leads to sympathoadrenal stimulation and inhibition of insulin secretion; and, thus, produces a net reduction in the growth- promoting effects. Fetal sheep were prepared with chronic peripheral a nd adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and e pinephrine secretion rates; and plasma norepinephrine, glucose, and im munoreactive insulin concentrations were determined at 30-min interval s during a 2-h baseline period and a 4-h period of hyperglycemia divid ed into 2-h segments of hypoxemia (with and without alpha-blockade) an d hyperoxia. Hypoxemia-hyperoxia sequences were varied randomly. Well- oxygenated fetuses responded to a threefold increase in glucose with a sixfold increase in plasma immunoreactive insulin. With hypoxemia, no repinephrine and epinephrine secretion were elevated and the insulin r esponse was blocked. With hypoxemia and phentolamine blockade, the ins ulin response was enhanced with a 10-fold increase above baseline. In severe maternal diabetes with vascular disease or with poor control an d very high glucose levels, the fetus is likely to be relatively hypox emic. Our experiments suggest that in this situation, the fetal insuli n response to hyperglycemia will be attenuated; this effect is mediate d, at least partly, through sympathoadrenal stimulation.