HP-MRI organ imaging to identify the risk of DKA with SGLT2 inhibitors in DM
SGLT2 inhibitors are important antidiabetic drugs with a broad range of effects. Many studies including the FDA warned that the use of SGLT2 inhibitors can increase the risk of diabetic ketoacidosis. The number of DKA incidence increased markedly worldwide, with one estimate suggesting that as many as 145,000 cases/year with T1DM in North America. T1DM patients are more likely to develop SGLT2 inhibitors associated with DKA due to insulin deficiency, which are amongst the most common causes of DKA. Indeed, it has been shown that the incidence of DKA in individuals with T1DM is higher than T2DM who are exposed to SGLT2 inhibitors. To date, no medical commodity available for non-invasive imaging of DKA. Therefore, a non-invasive real-time tissue interrogation technique is critically needed. To fill this gap, we have developed a non-invasive real-time HP-MRI organ imaging technique. Indeed, using HP-MRI we have detected divergent metabolic differences in gluconeogenic tissue between models of T1 and T2DM. In this project, our laboratory is interested in studying whether we can image the DKA non-invasively in vivo, in DM models. Using two contrasting DM rat models we are particularly interested to answer the following questions: (1) Whether we can image the ketone body turnover in kidney and in the liver following SGLT2 inhibitors treatment in real-time in vivo. (2) Whether the kidneys and livers of animals treated with SGLT2 inhibitors show increased ketone body turnover; and (3) Whether SGLT2-mediated gluconeogenesis signals go hand in hand with ketogenesis

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