Ketone Body Physiology and Testing

Introduction to Ketone Bodies

Total serum ketones should be less than 0.5 mmol/L under normal physiological conditions, according to the American Diabetes Association 1
Semiquantitative test-strip methods that utilize specific reactions for ketones are recommended for urine testing, as stated by the American Diabetes Association 1

People following very-low-carbohydrate (ketogenic) diets can experience ketosis, as noted by the American Diabetes Association 1
Diabetic Ketoacidosis (DKA) can occur, particularly when accompanied by hyperglycemia and symptoms like abdominal pain or nausea, as indicated by the American Diabetes Association 1
DKA is suggested by the presence of positive ketones in urine, typical symptoms, and hyperglycemia in patients with diabetes, with diagnosis requiring hyperglycemia, increased ketone bodies in blood or β-hydroxybutyrate (bOHB), and acidosis with an increased anion gap, as stated by the American Diabetes Association 1

Measuring β-hydroxybutyrate (bOHB) in blood is the preferred method for diagnosing DKA, being more accurate and reliable than urine ketones, according to the American Diabetes Association 1, 2
Urine ketone tests, which mainly measure acetoacetate, can give false-positive results with certain medications and false-negative results with prolonged exposure to air or acidic urine samples 3
Urine ketone levels can be estimated as + (~0.5 mmol/L), ++ (~0.7 mmol/L), and +++ (~3 mmol/L), with positive readings also found in normal individuals during fasting and in up to 30% of morning urine samples from pregnant women 1, 3
Blood ketone levels can be classified as: <0.5 mmol/L (normal), 0.5-1.5 mmol/L (mild elevation), 1.5-3.0 mmol/L (moderate elevation), and >3.0 mmol/L (dangerous level), with levels >7.0-8.0 mmol/L indicating severe ketoacidosis, as recommended by the American Diabetes Association 2, 4

Key laboratory tests for DKA diagnosis include:

Test	Description
Blood glucose	Measure blood glucose levels
Venous blood gases	Measure venous pH and bicarbonate levels
Electrolytes	Measure sodium, potassium, and chloride levels
Blood urea nitrogen	Measure BUN levels
Creatinine	Measure creatinine levels
Calcium	Measure calcium levels
Phosphorus	Measure phosphorus levels
Urinalysis	Measure urine ketones and other parameters

DKA is primarily caused by insulin deficiency or omission, with other risk factors including glucocorticoid therapy, acute illness or infection, surgery, trauma, or myocardial infarction, and SGLT2 inhibitor use, as stated by the American Diabetes Association 7, 8, 9, 1, 10
Ensuring adequate hydration and carbohydrate intake (150-200g daily) can help prevent DKA, with patients advised not to stop basal insulin and to follow detailed instructions on insulin dose adjustments during illness, as recommended by the American Diabetes Association 11, 12, 13, 14
High-risk patients for DKA include those with type 1 diabetes, history of previous DKA, SGLT2 inhibitor use, pregnancy, illness or infection, missed insulin doses, very low-carbohydrate diets, and alcohol consumption, as stated by the American Diabetes Association 12

Administering glucose-containing IV fluids and providing insulin therapy, such as continuous insulin infusion at 0.1 unit/kg/hr, are recommended for the treatment of DKA, with a strength of evidence level of high, as stated by the American Diabetes Association 4, 1
Correcting fluid and electrolyte imbalances and monitoring ketones using blood bOHB measurements are crucial in the management of DKA, as recommended by the American Diabetes Association 1
DKA is considered resolved when glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap <12 mEq/L, with a strength of evidence level of high, as stated by the American Diabetes Association 4, 5