Abstract P151: Cardiac Outcome in Offspring of Diabetic Pregnancy

Introduction: Obesity and associated pathologies like insulin resistance and diabetes reach epidemic proportions worldwide. Parental diabetes has been acknowledged as a risk factor for cardiovascular disease in offspring. Objective: We investigated the influence of a diabetic pregnancy on the heart in offspring using a transgenic rat model of diabetes. Methods: We elicited pre-gestational hyperglycemia and hyperinsulinemia in transgenic Tet29 rats by application of doxycycline, which induces a knock down of the insulin receptor via RNA interference. Wild-type Sprague-Dawley (SD) rats served as controls receiving doxycycline as well. Heart analysis was performed in fetuses and adult groups at the age of 8 months challenged by a high fat diet lasting over 12 weeks. Cardiac function was evaluated by speckle tracking echocardiography and gene expression levels were measured by qRT-PCR. Results: Tet29 mothers had higher blood glucose levels throughout and at the end of pregnancy (blood glucose 153.9±22.2 vs. 93.3±4.2 mg/dl). The quantity of pups was unaffected. Fetuses from diabetic mothers were growth restricted (brain-liver-ratio 0.554±0.011 vs. 0.515±0.009) and they had lower blood glucose levels at birth (63.3±3.0 vs. 91.2±3.2 mg/dl). Fetal heart-body-ratio remained unchanged. After 8 months of normal chow, no difference in cardiac performance was detectable. However, after feeding a high fat diet, the male offspring of diabetic mothers showed a reduced cardiac function revealed by echocardiography (ejection fraction 50.4±2.7 vs. 57.0±1.9 %, global longitudinal strain -16.2±0.5 vs. -18.0±0.5 %, left ventricular mass 1242.3±32.9 vs. 989.4±65.1 mg) and gene expression analysis (Myh-6/Myh-7 1.1±0.1 vs. 1.7±0.2). Discussion: We hypothesize that a diabetic pregnancy per se, has no acute effect on cardiovascular health in offspring in our model. However, challenges like a high fat diet, may unravel an increased susceptibility of these rats.