Significance of Ketones in Urine in a 58-Year-Old Woman Without Diabetes
In a 58-year-old woman with no known diabetes, urine ketones most likely represent benign starvation ketosis from reduced caloric intake, but you must immediately check blood glucose to exclude life-threatening diabetic ketoacidosis (DKA) or undiagnosed diabetes. 1, 2
Immediate Diagnostic Steps
Check blood glucose immediately - this single test distinguishes benign starvation ketosis (normal or low glucose) from DKA (glucose >250 mg/dL), which is a medical emergency. 3, 1
If Blood Glucose is Normal or Low (<140 mg/dL):
- Most likely diagnosis is starvation ketosis - the most common benign explanation occurring when patients feel unwell and eat less, causing the body to shift to fat metabolism for energy. 2
- Up to 30% of first morning urine specimens show positive ketones even in healthy individuals, and this increases during fasting states. 4, 2
- Starvation ketosis is characterized by serum bicarbonate usually not lower than 18 mEq/L and blood ketones ranging 0.3-4 mmol/L. 1
If Blood Glucose is Elevated (>250 mg/dL):
- This is a medical emergency requiring immediate DKA evaluation. 3, 1
- Obtain blood beta-hydroxybutyrate, electrolytes, and arterial blood gas immediately. 2
- DKA diagnostic criteria require: glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, and anion gap >10 mEq/L. 1
- This could represent new-onset diabetes (type 1 or type 2) presenting as DKA. 4
Critical Medication History
Ask specifically about SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) - these medications increase DKA risk and can cause euglycemic DKA where glucose may be <250 mg/dL despite severe ketoacidosis. 4, 5, 6, 7
- SGLT2 inhibitors decrease the hyperglycemia that typically accompanies DKA, making diagnosis more challenging. 4
- Blood ketone action thresholds: <0.5 mmol/L (no intervention), 0.5-1.5 mmol/L (initiate sick-day rules), ≥1.5 mmol/L (immediate medical attention). 3, 1
Additional Differential Diagnoses to Consider
Alcoholic Ketoacidosis:
- Individuals with alcoholic ketoacidosis will have positive urine ketone readings, but hyperglycemia is not usually present. 4
- Obtain alcohol history and toxicology screening if clinical suspicion exists. 5
Pregnancy:
- Positive urine ketone readings are found in up to 30% of first morning urine specimens from pregnant women (with or without diabetes). 4
Hypoglycemia:
- Ketones can appear after hypoglycemic episodes. 4
Important Testing Limitations
Urine dipsticks only detect acetoacetate, NOT beta-hydroxybutyrate, which significantly underestimates total ketone body concentration. 3, 2, 8
- Blood beta-hydroxybutyrate measurement is strongly preferred over urine testing for all clinical decision-making. 4, 3, 1, 2
- The nitroprusside method (standard urine dipstick) does not measure beta-hydroxybutyrate, the predominant ketone body in DKA. 4
- False-positive ketones can occur with sulfhydryl drugs like captopril. 3, 2
- False-negative results occur with prolonged air exposure of test strips or highly acidic urine. 3, 2
Risk Stratification Algorithm
High-Risk Features Requiring Immediate Evaluation:
- Blood glucose >250 mg/dL 3, 1
- Currently taking SGLT2 inhibitors 1, 2
- Symptoms of DKA: polyuria, polydipsia, weakness, abdominal pain, Kussmaul respirations, altered mental status 1
- History of prior DKA 1
Lower-Risk Features Suggesting Starvation Ketosis:
- Normal blood glucose 1
- Recent decreased oral intake 1
- No abdominal pain or altered mental status 1
- No diabetes history 1
Common Pitfalls to Avoid
- Do not rely solely on urine ketone testing - always obtain blood glucose and consider blood beta-hydroxybutyrate measurement for accurate assessment. 4, 3, 2
- Do not dismiss ketones in patients on SGLT2 inhibitors - they can develop euglycemic DKA with glucose levels as low as 75 mg/dL. 5
- Do not assume absence of diabetes history excludes DKA - this could be new-onset diabetes or undiagnosed latent autoimmune diabetes in adults (LADA). 5