What does it mean if a patient, possibly with a history of diabetes, has ketones in their urine?

Ketones in Urine: Clinical Significance and Management

The presence of ketones in urine indicates mild ketosis that may represent either a benign physiological response (such as fasting or pregnancy) or a warning sign of impending diabetic ketoacidosis (DKA) in high-risk patients, particularly those with type 1 diabetes, requiring immediate risk stratification based on diabetes history, blood glucose level, and clinical symptoms. 1

Immediate Risk Stratification Required

The critical first step is determining whether this represents dangerous pathological ketosis versus benign physiological ketosis:

High-Risk Patients Requiring Immediate Evaluation:

• Known type 1 diabetes - even mild ketones may signal insufficient insulin and impending DKA, which is a medical emergency 1
• Currently on SGLT2 inhibitors - these medications increase DKA risk and can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis 2, 3, 4
• History of prior DKA episodes 2
• Blood glucose >250 mg/dL - this indicates a medical emergency requiring immediate DKA evaluation with blood beta-hydroxybutyrate, electrolytes, and arterial blood gas 5, 2

Lower-Risk Patients (Likely Starvation Ketosis):

• No diabetes history with normal blood glucose 2
• Recent decreased oral intake - starvation ketosis from reduced caloric intake is the most common benign explanation 5
• First morning urine specimen - up to 30% of first morning urine specimens show positive ketones even in healthy individuals 1, 2
• Pregnancy - up to 30% of first morning urine specimens from pregnant women show positive ketones 1, 2

Critical Testing Limitations and Recommendations

Blood ketone testing is strongly preferred over urine testing for all clinical decision-making because urine dipsticks only detect acetoacetate, NOT beta-hydroxybutyrate, which is the predominant ketone body in DKA and can significantly underestimate total ketone concentration 5, 2, 6, 7. This creates a dangerous clinical pitfall where urine tests may appear falsely reassuring.

Additional Testing Pitfalls:

• False-positive results occur with highly colored urine and sulfhydryl drugs like captopril 1, 5
• False-negative results occur with prolonged air exposure of test strips or highly acidic urine 1, 5
• Urine ketones lag behind clinical status - urine ketone tests might be increasing even as DKA is resolving because beta-hydroxybutyrate is oxidized to acetoacetate during recovery 6

DKA Diagnostic Criteria

If DKA is suspected, all of the following criteria must be present for diagnosis 2, 8:

• Plasma glucose >250 mg/dL (though SGLT2 inhibitors can cause euglycemic DKA with lower glucose) 2
• Arterial pH <7.30 2
• Serum bicarbonate <15 mEq/L 2
• Positive urine or serum ketones 2
• Anion gap >10 mEq/L 2

Clinical Presentation of DKA:

• Early signs: glycosuria and ketonuria 9
• Progressive symptoms: polyuria, polydipsia, weakness, abdominal pain, Kussmaul respirations, altered mental status, fruity breath odor 2, 9
• Symptoms develop gradually over hours to days 9

Management Based on Risk Category

For Diabetic Patients with Ketones:

Blood ketone action thresholds (when available) 2:

• <0.5 mmol/L: No intervention needed
• 0.5-1.5 mmol/L: Initiate sick-day rules (increase fluids, monitor every 3-4 hours, consider additional rapid-acting insulin)
• ≥1.5 mmol/L: Immediate medical attention required

Specific interventions for mild ketosis 1:

• Increase oral fluid intake to prevent dehydration
• Monitor blood glucose and ketone levels every 3-4 hours
• Consider additional short or rapid-acting insulin if ketone levels increase or symptoms develop
• For patients with normal blood glucose but elevated ketones, consume some carbohydrates along with insulin to help suppress ketone production

Seek immediate medical care if 1:

• Ketone levels increase despite interventions
• Any symptoms of ketoacidosis develop (nausea, vomiting, abdominal pain, confusion)
• Blood glucose remains >250 mg/dL

For Non-Diabetic Patients:

• If fasting or decreased oral intake: This likely represents normal physiological ketosis requiring no intervention beyond resuming normal eating 5, 2
• If pregnant: This is a common finding in up to 30% of first morning specimens and typically benign 1, 2
• If on SGLT2 inhibitors for any reason: Requires immediate evaluation as these medications increase ketoacidosis risk even in non-diabetics 2

Special Medication Considerations

SGLT2 inhibitors create unique diagnostic challenges 2:

• They decrease the hyperglycemia that typically accompanies DKA, making diagnosis more challenging
• They can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis
• Patients on these medications with any ketones and symptoms (nausea, vomiting, malaise) require immediate evaluation

Insulin management during illness 9:

• Insulin requirements may be altered during illness, emotional disturbances, or other stresses
• Hyperglycemia and ketoacidosis can develop if patients take less insulin than needed during illness or infection
• Never omit insulin doses even when not eating well