Early Life Development of Cardiac Hypertrophy in Rat Offspring from Pregnancies Complicated by Gestational Diabetes Mellitus

Abstract

Metabolic and cardiovascular health is influenced by early life events. During the late prenatal and early postnatal period of life, growth of the heart switches from hyperplastic to hypertrophic growth. Therefore, regulation of cardiomyocyte size may be permanently programmed during the early life environment. Cardiac hypertrophy is characterized by increased myocardial cell size and influences the development of diabetic cardiomyopathy. Currently, little is known regarding the developmental origins of diabetic cardiomyopathy. Exposure to gestational diabetes mellitus (GDM) increases the susceptibility of rat offspring to the development of cardiac hypertrophy. Maternal GDM was caused by feeding high-fat- (45%) and sucrose (HFS)-containing diets to female rats for 6 weeks prior to and throughout pregnancy. Lean control pregnant rats received low fat (LF; 10%) diets. Newborn pup hearts were analyzed for cardiac hypertrophy. The remaining offspring were weaned at 3 weeks of age and randomly assigned to LF or HFS diets for a period of 12 weeks. Consumption of HFS diets by pregnant rats caused elevated gestational weight gain and mid-gestational hyperglycemia. The heart weight and heart weight:body weight ratio was 1.3-fold (p<0.01) greater in newborn neonates from GDM mothers. The postnatal consumption of HFS diets by offspring from GDM mothers increased the postnatal heart weight:tibia length ratio 1.3-fold (p<0.05) compared to offspring from lean mothers. GDM increases the susceptibility of rat offspring to cardiac hypertrophy. These findings have important implications since GDM may be an important factor that contributes to the early onset of diabetic cardiomyopathy.