Pathogenesis of Disproportionate Septal Hypertrophy in Infants of Streptozotocin-Induced Diabetic Mother Rats

Transient hypertrophic cardiomyopathy in human infants born of diabetic mothers is well known. In order to elucidate the pathogenesis of this unique type of myocardial disease, morphological and endocrinological studies were performed on fetuses and infants of streptozotocin-induced diabetic rats in the present study.Disproportionate ventricular septal thickening (DVST) was observed in 76% of the fetuses of diabetic mothers (FDM) on day 21 of gestation and in 60% of 2-day-old infants born of diabetic mothers (IDM). Although DVST was a usual finding in fetuses on day 18 of gestation or before, it was infrequent in control fetuses on day 21 of gestation. Immature side-to-side or side-to-end type intercellular connections were more frequently seen in the ventricular cardiac muscles of FDM on day 21 of gestation and in 2-day-old IDM than in the controls. Serum insulin-like growth factor I (IGF-I) and insulin levels and pancreatic insulin content were significantly lower in FDM and IDM than in the controls, and significant negative correlations were found between serum IGF-I and insulin levels and interventricular septal to left ventricular free wall thickness ratios.The above findings indicate that DVST in FDM and IDM represents immaturity of cardiac architecture. It is also quite conceivable that insufficient secretion of IGF-I and insulin play significant roles in this immaturity.