Acute hyperketonemia does not affect glucose or palmitate uptake in abdominal organs or skeletal muscle

Abstract

Context: It has recently been hypothesized that ketone bodies may have independentcardioprotective effects due to increased myocardial efficiency and that this may explain theimproved survival of individuals with type 2 diabetes treated with mildly ketogenic sodium-glucose cotransporter-2 inhibitors.Objective: To determine whether ketone bodies are selectively utilized in tissues critical forpreservation of conscience and circulation. We investigated the effect of acute hyperketonemiaon substrate metabolism in less prioritized tissues such as abdominal organs, adipose tissue, andskeletal muscle.Design: Acute, randomized, single-blinded, crossover design.Setting: Ambulatory care.Participants: Eight healthy participants completed the study. Two additional participantswithdrew because of claustrophobia during the scans.Intervention: Infusions of saline and ketone bodies during a hyperinsulinemic-euglycemicclamp.Main Outcome Measures: Organ-specific glucose and palmitate uptake was determinedby dynamic positron emission tomography/computed tomography (PET/CT) scans with18F-fluorodeoxyglucose (18F-FDG) and 11C-palmitate. Blood flow to abdominal organs wasmeasured with O-15-labeled water (15O-H2O) perfusion PET. The study was performed as a posthoc analysis.Results: We found that ketone body infusion did not affect glucose uptake, palmitate uptake,or blood flow to abdominal organs and skeletal muscles.Conclusion: Acute hyperketonemia does not affect glucose or palmitate uptake in skeletalmuscle or abdominal tissues, supporting the notion that ketone bodies are selectively used bycritical organs such as the heart and brain.