What causes ketones in urine?

Causes of Ketones in Urine

Ketones in urine are primarily caused by diabetic ketoacidosis, starvation/fasting, very low carbohydrate diets, prolonged exercise, and alcoholic ketoacidosis. 1

Main Causes of Ketonuria

Diabetic Causes

• Type 1 diabetes: Especially in those with history of previous DKA 1
• Insulin insufficiency: Leading to increased lipolysis and conversion of free fatty acids to ketone bodies 2
• SGLT2 inhibitor use: Can cause euglycemic DKA (ketoacidosis with blood glucose <200 mg/dL) 1
• Pregnancy with diabetes: Higher risk of euglycemic DKA 1
• Missed insulin doses: Leading to insulin deficiency 1

Non-Diabetic Causes

• Prolonged fasting: When carbohydrates are unavailable, the body turns to fat metabolism 1
• Very low carbohydrate diets: Diets with <20-30g carbohydrates daily 1, 3
• Prolonged exercise: Depletes glycogen stores, leading to ketone production 1, 4
• Alcoholic ketoacidosis: Alcohol consumption can trigger ketosis 1, 5
• Starvation: Limited carbohydrate availability forces the body to use ketones as an energy source 4, 6
• Pregnancy: Normal physiological state that can have mild ketosis 4
• Neonatal state: Newborns can have elevated ketones 4

Pathophysiology of Ketone Production

Ketone bodies are produced by the liver when glucose is not readily available:

• During insulin deficiency, lipolysis increases, releasing free fatty acids
• These fatty acids are converted in the liver to ketone bodies (mainly beta-hydroxybutyrate and acetoacetate) 2
• Beta-hydroxybutyrate is the predominant ketone in blood during ketoacidosis 2
• Acetoacetate is the predominant ketone found in urine 2
• Acetone (the third ketone body) forms through spontaneous decarboxylation of acetoacetate and can be measured in breath 2

Clinical Significance of Ketone Levels

Ketone levels in blood can be classified as follows:

• <0.5 mmol/L: Normal range
• 0.5-1.5 mmol/L: Mild elevation (may be due to fasting or exercise)
• 1.5-3.0 mmol/L: Moderate elevation (requires monitoring)

• 3.0 mmol/L: Dangerous level (requires immediate medical attention)

• 7.0-8.0 mmol/L: Severe ketoacidosis 1

Special Considerations

Euglycemic DKA

• Characterized by metabolic acidosis, ketosis, but blood glucose <250 mg/dL 3, 5
• Risk factors include:
  • SGLT2 inhibitor use 1
  • Pregnancy 1
  • Severe carbohydrate restriction/ketogenic diets 3
  • Cocaine abuse (due to anorexic effects) 5
  • Starvation in insulin-dependent diabetics 5

Ketogenic Diet-Induced Ketosis

• Intentional dietary ketosis is increasingly common
• Can mask symptoms of developing DKA in diabetic patients 3
• May precipitate euglycemic DKA in susceptible individuals 3

Common Pitfalls in Detecting Ketones

• Relying only on urine ketone testing: The nitroprusside test only detects acetoacetate, not beta-hydroxybutyrate (the predominant ketone in DKA) 4
• Missing euglycemic DKA: Failing to check for ketones in patients with normal blood glucose 1
• Misinterpreting ketone trends during treatment: As DKA resolves, beta-hydroxybutyrate is oxidized to acetoacetate, so urine ketones may appear to increase even as the condition improves 2

When to Seek Medical Attention

Patients with large ketonuria should receive immediate medical attention, especially if they have:

• Type 1 diabetes
• Symptoms of acidosis (nausea, vomiting, abdominal pain, rapid breathing)
• Blood ketone levels >3.0 mmol/L
• Pregnancy
• Use of SGLT2 inhibitors 1

Treatment includes insulin administration, hydration, and identification of underlying causes to prevent progression to full DKA 1.