New translational research presented Aug. 26 at ESC Congress 2018 provides a characterization of the cardiac energetics and fuel metabolic flux in an experimental model of diabetes treated with and without the SGLT2 inhibitor empagliflozin. The study was also simultaneously published in JACC: Basic to Translational Science.

Given the growing interest in the hypothesis that SGLT2 inhibitors improve cardiac function through an effect on cardiac energy production, in part through increasing ketone body production/oxidation, researchers evaluated cardiac energy production and bioenergetics in an experimental model of diabetes treated with empagliflozin. They treated diabetic mice with or without empagliflozin and measured rates of glucose oxidation, fatty acid oxidation, ketone oxidation, glycolysis and cardiac function.

Results showed rates of glucose and ketone oxidation in the hearts of untreated diabetic mice were significantly decreased. However, fatty acid oxidation was increased with a significant overall reduction in cardiac ATP production compared to non-diabetic mice. Additionally, researchers noted that empagliflozin increased overall cardiac ATP production by roughly 30 percent and prevented cardiac failure.

Based on the findings, researchers suggest that "empagliflozin enhances the cardiac energy pool by increasing cardiac energy production from glucose and fatty acid oxidation, but not ketone oxidation. "These data provide translational clues as to how SGLT2 inhibitors may prevent cardiac failure, through augmenting glucose and fatty acid oxidation," researchers said. "Contrary to prior hypotheses, increased rates of cardiac ATP production, as opposed to increased cardiac efficiency, may explain the beneficial effects of SGLT2 inhibitors on improving cardiac function in diabetes."

In a related editorial, Peter A. Crawford, MD, PhD, writes that "ongoing experiments need to test for combinatorial effects of SGLT2 inhibition, and also account for variations posed by the model studied, including the nature of the metabolic and hemodynamic insult, as well as species- and sex-dependent differences."

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism

Keywords: ESC18, ESC Congress, Sodium-Glucose Transporter 2, Diabetes Mellitus, Glucose, Ketones, Metabolic Syndrome

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