Abstract 9241: High Sugar Intake May Improve Survival and Does Not Adversely Affect Cardiac and Metabolic Dysfunction in Genetic Cardiomyopathy

Abstract

High sugar intake increases the risk of heart disease in humans, and in some animal models of hypertension it increases oxidative stress and accelerates the development of heart failure. Recent studies suggest that glucose 6-phosphate dehydrogenase (G6PD) may be responsible for ROS generation, as it produces NADPH, which is used by NADPH oxidase to produce superoxide, while on the other hand it can facilitate the removal of reactive oxygen species (ROS) via the glutathione pathway. We hypothesized that a high sugar diet would increase flux through G6PD to increase myocardial [NADPH] and ROS production, and accelerate cardiac dysfunction and death. Cardiomyopathic TO-2 hamsters, a nonhypertensive model of genetic cardiomyopathy, were fed a either a high starch/sugar free diet or a high sugar diet (57% of energy from fructose +sucrose; n=12/group for echocardiography and biochemical analysis; n=30/cardiomyopathic group and n=10 healthy controls for survival analysis). However, after 24 weeks, the high sugar diet alleviated the decrease in ejection fraction associated with cardiomyopathy, and there was a strong trend for high sugar intake to increase survival (p=0.087)(Figure). High sugar intake increased left ventricular superoxide production, but did not affect [NADPH] or lipid peroxidation products. Cardiomyopathy resulted in metabolic abnormalities including decreased left ventricular mitochondrial oxidative enzyme activities, high circulating glucose, triglycerides and free fatty acids and decreased insulin, however the high sugar diet did not affect any of these parameters. These results indicate that despite a sugar-induced increase in superoxide production, there was no worsening of cardiac function or survival. In contrast, the high sugar diet improved systolic dysfunction and show a strong trend for prolonged survival.