From the Guidelines
Elevated beta-hydroxybutyrate (BHBT) is primarily caused by ketosis, a metabolic state where the body burns fat for energy instead of carbohydrates, with the most common causes including prolonged fasting, very low-carbohydrate diets, uncontrolled diabetes, excessive alcohol consumption, and starvation. The most recent and highest quality study, 1, published in 2023, highlights the importance of measuring ketone bodies, including BHBT, in the diagnosis and management of diabetes mellitus. According to this study, the presence of urine ketones is highly sensitive for diabetic ketoacidosis (DKA) or significant ketosis, with a high negative predictive value, suggesting its utility in ruling out DKA.
Causes of Elevated BHBT
- Prolonged fasting
- Very low-carbohydrate diets (ketogenic diets)
- Uncontrolled diabetes (particularly type 1)
- Excessive alcohol consumption
- Starvation
- Certain metabolic disorders
- Prolonged vomiting
- Severe infections
- Some medications like SGLT2 inhibitors
In diabetic patients, insulin deficiency prevents glucose utilization, forcing the body to break down fat, which produces ketone bodies, including BHBT, as noted in 1. This can progress to diabetic ketoacidosis, a medical emergency requiring immediate treatment with insulin, fluids, and electrolyte replacement. Other studies, such as 1, published in 2020, emphasize the importance of monitoring BHBT levels in children and adolescents with type 1 diabetes, especially during physical activity, to prevent hypoglycemia and ketosis.
Physiologically, when glucose is unavailable or cannot be used effectively, the liver converts fatty acids into ketone bodies (including BHBT) as an alternative energy source for the brain and other organs, as explained in 1. While mild elevation may be intentional in ketogenic diets, significant elevation, especially with symptoms like nausea, vomiting, abdominal pain, confusion, or rapid breathing, requires immediate medical attention to prevent serious complications.
From the Research
Causes of Elevated Beta-Hydroxybutyrate (BHB)
- Elevated BHB levels can be caused by various factors, including diabetic ketoacidosis (DKA) 2, 3, 4, 5, 6
- The use of sodium glucose cotransporter inhibitors, such as sotagliflozin, can increase BHB levels in insulin-requiring patients 2
- Baseline BHB levels and changes in BHB over time can be associated with an increased risk of DKA 2, 4
- Age, insulin pump use, and sotagliflozin use can also be associated with DKA episodes 2
Diagnostic Criteria for DKA
- BHB levels can be used to diagnose DKA, with threshold values of 3.0 mmol/L in children and 3.8 mmol/L in adults 3
- A BHB value of <1.5 mmol/L can be used to define resolution of DKA 4
- BHB demonstrates strong discrimination for DKA, with an area under the curve of 0.95 6
- A BHB value of 5.3 mmol/L can predict DKA with optimal accuracy, with a sensitivity of 76.7% and specificity of 96.4% 6
Monitoring and Management of DKA
- Frequent biochemical monitoring is required for DKA management 4
- BHB testing and monitoring can be important for individualizing patient education on DKA risk, mitigation, identification, and treatment 2
- Plasma BHB can provide a direct measure of the pathophysiologic derangement in DKA, compared to nonspecific measurements of blood pH and bicarbonate 6