Acute Hyperketonemia Does Not Affect Glucose or Palmitate Uptake in Abdominal Organs or Skeletal Muscle

Context It has recently been hypothesized that ketone bodies may have independent cardioprotective effects due to increased myocardial efficiency and that this may explain the improved 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 for preservation of conscience and circulation. We investigated the effect of acute hyperketonemia on substrate metabolism in less prioritized tissues such as abdominal organs, adipose tissue, and skeletal muscle. Design Acute, randomized, single-blinded, crossover design. Setting Ambulatory care. Participants Eight healthy participants completed the study. Two additional participants withdrew because of claustrophobia during the scans. Intervention Infusions of saline and ketone bodies during a hyperinsulinemic-euglycemic clamp. Main Outcome Measures Organ-specific glucose and palmitate uptake was determined by dynamic positron emission tomography/computed tomography (PET/CT) scans with 18F-fluorodeoxyglucose (18F-FDG) and 11C-palmitate. Blood flow to abdominal organs was measured with O-15-labeled water (15O-H2O) perfusion PET. The study was performed as a post hoc 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 skeletal muscle or abdominal tissues, supporting the notion that ketone bodies are selectively used by critical organs such as the heart and brain.