One infant with nesidioblastosis, and five of 18 infants of diabetic mothers had echocardiographically determined septal hypertrophy (greater than or equal to 6 mm). No correlation was found between the septal hypertrophy and the presence of hypocalcemia, polycythemia, birth asphyxia, or other observed clinical findings. All of the infants with septal hypertrophy, however, had profound hypoglycemia shortly after birth in contrast to those infants without septal hypertrophy. Macrosomic IDM have intrauterine hyperglycemia and hyperinsulinemia. The presence of profound neonatal hypoglycemia is consistent with the metabolic effects of significant neonatal hyperinsulinemia which is also present in the fetus. Infants with nesidioblastosis also have fetal hyperinsulinemia. Recent investigations have suggested an important role for insulin in the developing heart since it is rich in insulin receptors and contains marked insulin degrading capacity. Although fetal hyperglycemia has been suggested as the cause of septal hypertrophy in IDM, we hypothesize that fetal hyperinsulinemia contributes directly to the spinal hypertrophy.