Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers

Abstract

To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.