Hyperketonemia as the diagnostic basis for hypothermia: An experimental study in diabetic and control mice

Hypothermia is an important cause of death in forensic pathology. For the forensic diagnosis of hypothermia, some reports point out the possibility that hypothermia without diabetes may cause ketoacidosis. In this study, we evaluated the diagnostic value of ketoacidosis in a murine model of hypothermia, using the cold stress at 4 °C for 3 or 5 hrs in genetically diabetic (BKS.Cg-+Lepr^db/+Lepr^db/J) mice, compared with control (BKS.Cg- Dock7^m+/Dock7^m+/J) mice. The core temperature decrease was larger in diabetic mice than in control mice. We observed a novel finding that ketoacidosis assessed by elevated serum 3-hydroxybutyrate (3HB) occurs in hypothermia both in diabetic and control mice. Diabetic mice showed a prominent elevation of serum 3HB under cold stress. The protein expressions of monocarboxylate cotransporter 1 (MCT1), the channel protein used for the uptake of 3HB in skeletal muscles, showed a statistically significant decrease under cold stress for 3 hrs in control mice, indicating that the serum 3HB increase may be partially due to the decrease in the cellular uptake through the channel protein. Our results suggest the usefulness of hyperketonemia for the diagnosis of hypothermia not only in diabetic but also in non-diabetic cases.