What does the presence of ketones in the urine indicate?

What Ketones in Urine Mean

Ketones in urine indicate that your body is breaking down fat for energy instead of using glucose, which is normally present at very low concentrations but becomes elevated in conditions ranging from benign fasting states to life-threatening diabetic ketoacidosis (DKA). 1

Basic Physiology

Ketone bodies—acetoacetate (AcAc), beta-hydroxybutyrate (β-OHB), and acetone—are produced by the liver from fatty acid breakdown when carbohydrate availability is limited. 1

• Normal concentrations: Ketones are always present in blood and urine but typically at very low levels (total serum ketones <0.5 mmol/L). 1
• The three ketone bodies exist in specific proportions: β-OHB and AcAc are usually present in approximately equal amounts (1:1 ratio), while acetone is present in much smaller quantities. 1, 2

Clinical Significance: When to Worry

In People with Diabetes (High Risk)

Elevated urine ketones in diabetic patients—especially those with type 1 diabetes, history of DKA, or taking SGLT2 inhibitors—suggest impending or established diabetic ketoacidosis, which is a medical emergency requiring immediate action. 1, 3

• The presence of urine ketones is highly sensitive for DKA with high negative predictive value, making it useful for ruling out DKA. 1, 3
• Two mechanisms drive ketone elevation in diabetes: increased production from triglycerides and decreased utilization in the liver, both resulting from absolute or relative insulin deficiency plus elevated counterregulatory hormones (cortisol, epinephrine, glucagon, growth hormone). 1

In Non-Diabetic Individuals (Usually Benign)

Positive urine ketones can represent normal physiological responses:

• Fasting or starvation: Up to 30% of first morning urine specimens show positive ketones during fasting states. 3, 4
• Pregnancy: Up to 30% of first morning specimens from pregnant women may show ketones. 3
• Ketogenic diets: People following very-low-carbohydrate diets for weight loss or diabetes control commonly have detectable urine ketones. 1
• Prolonged exercise: Activates lipid metabolism and ketone production. 5, 6

Critical Limitation of Urine Testing

Standard urine dipsticks using the nitroprusside reaction only detect acetoacetate and NOT beta-hydroxybutyrate, which is the predominant ketone body in DKA. 1, 3, 5

• This creates a dangerous paradox: As DKA resolves with treatment, β-OHB is oxidized to acetoacetate, so urine ketones may actually increase even as the patient improves. 5
• The equilibrium shifts toward β-OHB formation in conditions that alter hepatic mitochondrial redox state (hypoxia, fasting, DKA, alcoholic ketoacidosis), meaning urine tests can severely underestimate total ketone body concentration. 1
• Blood ketone testing is strongly preferred over urine testing for diagnosis and monitoring of ketosis because it directly measures β-OHB. 3, 7

When to Test for Ketones

The American Diabetes Association recommends that ketosis-prone individuals (type 1 diabetes, history of DKA, or on SGLT2 inhibitors) should measure ketones when they have:

• Unexplained hyperglycemia 1
• Symptoms of ketosis: abdominal pain, nausea 1
• Acute illness or stress 3
• Blood glucose persistently elevated despite insulin 7

Management Algorithm for Elevated Ketones

For Diabetic Patients with Positive Ketones:

1. Increase oral fluid intake to prevent dehydration 7
2. Monitor blood glucose and ketone levels every 3-4 hours 3, 7
3. Administer additional short or rapid-acting insulin if blood glucose is elevated 7
4. For normal blood glucose but elevated ketones: Consider consuming some carbohydrates along with insulin to help suppress ketone production 3

Seek Immediate Medical Attention If:

• Unable to tolerate oral hydration due to vomiting 7
• Blood glucose levels do not improve with insulin 7
• Altered mental status develops 7
• Ketone levels continue to increase despite interventions 7
• Symptoms of DKA develop: drowsy feeling, flushed face, thirst, loss of appetite, fruity breath odor, heavy breathing, rapid pulse 8

Important Caveats and Pitfalls

False-Positive Results:

• Highly colored urine 3, 4
• Sulfhydryl drugs including captopril (antihypertensive) 3
• Salicylates 8

False-Negative Results:

• Test strips exposed to air for extended periods 3
• Highly acidic urine specimens 3
• Testing at suboptimal times (lowest detection rates occur mid-morning around 10:00 AM) 9

Special High-Risk Populations:

• SGLT2 inhibitor users: At increased risk for euglycemic DKA (DKA with relatively normal blood glucose levels). 7
• Pregnant women: May present with euglycemic DKA and should seek immediate medical attention if ketones are elevated. 7

Distinguishing Different Types of Ketosis

Starvation ketosis typically produces less severe acidosis than DKA, with serum bicarbonate usually not lower than 18 mEq/L, and blood glucose is normal to mildly elevated (rarely >250 mg/dL). 4

• In acute DKA, the ketone body ratio (β-OHB:AcAc) rises from normal (1:1) to as high as 10:1. 2
• Alcoholic ketoacidosis must also be distinguished from diabetic and starvation ketosis. 4, 6

Optimal Testing Timing

For those monitoring ketogenic diet compliance, the highest detection rates (>90%) for ketonuria occur at 7:00 AM, 10:00 PM, and 3:00 AM, with the highest absolute levels at 10:00 PM and 3:00 AM. 9