From the Guidelines
Elevated beta-hydroxybutyric acid (BHB) is primarily caused by ketosis, a metabolic state where the body burns fat for energy instead of carbohydrates, with the most common cause being diabetic ketoacidosis (DKA), as supported by 1.
Causes of Elevated BHB
The causes of elevated BHB can be categorized into several groups, including:
- Diabetic ketoacidosis (DKA), a dangerous complication of type 1 diabetes where insulin deficiency leads to excessive fat breakdown and ketone production, as discussed in 1 and 1.
- Alcoholic ketoacidosis from prolonged alcohol consumption with poor nutrition.
- Starvation ketosis from extended fasting or severe caloric restriction.
- Intentional nutritional ketosis from very low-carbohydrate diets (below 50g daily).
- Certain metabolic disorders like MCAD deficiency or other fatty acid oxidation disorders, as mentioned in 1.
- Pregnancy complications, particularly hyperemesis gravidarum with prolonged vomiting, may trigger ketosis.
Pathogenesis
The pathogenesis of elevated BHB involves a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone, as explained in 1 and 1. This leads to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues, resulting in hyperglycemia and parallel changes in osmolality of the extracellular space.
Treatment
Treatment depends on the underlying cause, with DKA requiring immediate insulin, fluids, and electrolyte management, as stated in 1 and 1. Alcoholic ketoacidosis needs hydration, nutrition, and glucose, while nutritional ketosis typically resolves with carbohydrate consumption. It is essential to address the underlying cause to prevent morbidity, mortality, and to improve quality of life, as emphasized in 1 and 1.
From the FDA Drug Label
Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin Hyperglycemia can be brought about by any of the following: ... In patients with type 1 or insulin-dependent diabetes, prolonged hyperglycemia can result in DKA (a life-threatening emergency) The first symptoms of DKA usually come on gradually, over a period of hours or days, and include ... With DKA, blood and urine tests show large amounts of glucose and ketones.
The causes of elevated beta hydroxybutyric (a type of ketone) include:
- Hyperglycemia (high blood sugar)
- Diabetic Ketoacidosis (DKA), which can be caused by:
- Omitting insulin or taking less than prescribed
- Eating more than the meal plan suggests
- Developing a fever, infection, or other stressful situation
- Prolonged hyperglycemia in patients with type 1 or insulin-dependent diabetes 2 2
From the Research
Causes of Elevated Beta Hydroxybutyric
- Elevated beta hydroxybutyric (BHB) levels can be caused by various factors, including diabetic ketoacidosis (DKA) 3, 4, 5, 6, 7
- The use of sodium glucose cotransporter inhibitors, such as sotagliflozin, can increase BHB levels in insulin-requiring patients 3
- Baseline BHB levels and changes in BHB levels over time can be associated with an increased risk of DKA 3
- Age, insulin pump use, and baseline BHB levels can also be associated with DKA episodes 3
- Elevated 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 4
- BHB levels can provide a direct measure of the pathophysiologic derangement in DKA, and can be used to predict DKA with high accuracy 7
Diagnostic Criteria for DKA
- DKA can be diagnosed using various criteria, including elevated blood glucose levels, the presence of high urinary or blood ketoacids, and a high anion gap metabolic acidosis 6
- BHB levels can be used as a diagnostic criterion for DKA, with a value of 5.3 mmol/L predicting DKA with optimal accuracy 7
- The sensitivity, specificity, and positive and negative predictive values of BHB levels in diagnosing DKA can be high, making it a useful diagnostic tool 7
Risk Factors for DKA
- Various risk factors can contribute to the development of DKA, including baseline BHB levels, changes in BHB levels over time, age, insulin pump use, and the use of certain medications such as sotagliflozin 3, 6
- Early diagnosis and management of DKA are crucial to improve patient outcomes, and BHB levels can be used to monitor the effectiveness of treatment 6