Concentration‐dependent effects of dichloroacetate in type 2 diabetic hearts assessed by hyperpolarized [1‐¹³C]‐pyruvate magnetic resonance imaging

Abstract

Personalized medicine or individualized therapy promises a paradigm shift in healthcare. This is particularly true in complex and multifactorial diseases such as diabetes and the multitude of related pathophysiological complications. Diabetic cardiomyopathy represents an emerging condition that could be effectively treated if better diagnostic and, in particular, better therapeutic monitoring tools were available. In this study, we investigate the ability to differentiate low and high doses of metabolically targeted therapy in an obese type 2 diabetic rat model. Low-dose dichloroacetate (DCA) treatment was associated with increased lactate production, while no or little change was seen in bicarbonate production. High-dose DCA treatment was associated with a significant metabolic switch towards increased bicarbonate production. These findings support further studies using hyperpolarized [1-13 C]-pyruvate magnetic resonance imaging to differentiate treatment effects and thus allow for personalized titration of therapeutics.