Postnatal decrease in insulin binding to erythrocytes in infants of diabetic mothers.

To clarify the role of insulin receptors in the macrosomia and the tendency to hypoglycemia in infants of mothers with insulin-treated diabetes mellitus (IDM) we studied insulin binding in erythrocytes from mixed umbilical blood and from peripheral venous blood collected when the infants were 3-14 days old. Normal infants were matched for gestational and postnatal age. The IDM infants were macrosomic, with significantly higher birth weights relative to gestational age than the control infants. Plasma free insulin concentrations in cord blood were 15-fold higher in the IDM than in the normal infants and more than 3-fold higher in the peripheral venous blood at the median age of 4 days. Hypoglycemia occurred in 12 of the 17 IDM and in none of the normal infants. In umbilical blood insulin binding to erythrocytes was similar in the IDM and normal infants. In both groups insulin binding decreased during the first postnatal weeks, but the decrease was significantly greater in the IDM than in the normal infants. The decrease in insulin binding to erythrocytes was a consequence of decreased receptor affinity as well as decreased receptor concentration in the IDM infants, but was mainly due to decreased receptor concentration in the normal infants. We conclude that insulin binding to its erythrocyte receptor in cord blood in IDM infants is similar to that in normal infants in spite of the simultaneous gross hyperinsulinemia in the IDM infants. The resulting increase in insulin action would then contribute to the tendency toward hypoglycemia and may be partly responsible for the macrosomia in IDM infants. The marked postnatal decrease in insulin binding in IDM infants is a possible explanation for their diminishing risk of hypoglycemia after the first few days of life in spite of persisting hyperinsulinemia.