Programming of adult cardiovascular disease following exposure to late-gestation hyperglycemia.

BACKGROUND In utero exposure to hyperglycemia is becoming increasingly prevalent as the number of women entering pregnancy with type II diabetes, or developing gestational diabetes, increases. Both animal studies and epidemiologic investigations have found cardiovascular abnormalities in adult offspring of hyperglycemic mothers (OHM). OBJECTIVE We hypothesized that adult OHM would have abnormal cardiac function in vivo and increased susceptibility to ischemia. METHODS Pregnant rats were made diabetic on day 12 of gestation. Serum glucose was monitored twice daily and insulin provided to maintain serum glucose at 200-400 mg/dl. Offspring were fostered to normal mothers after birth. Adult OHM were studied at 8-10 months of age with echocardiography to assess in vivo cardiac function and isolated hearts to determine the response to ischemia. RESULTS Echocardiography found significant diastolic dysfunction in male OHM compared to male controls. In isolated hearts, baseline cardiac function and left ventricular compliance was significantly diminished in male OHM compared to controls. Ischemia caused a significant decline in heart function in controls and female OHM, while function in male OHM remained unchanged. CONCLUSIONS Adult male OHM demonstrate programmed cardiac dysfunction. Given the growing number of pregnancies complicated by hyperglycemia, additional assessment of cardiac function of adults born to diabetic mothers may be warranted.