What is the appropriate management for a non-diabetic patient with positive urine glucose and ketones?

Management of Non-Diabetic Patient with Positive Urine Glucose and Ketones

In a non-diabetic patient with positive urine glucose and ketones, immediately measure blood glucose and blood beta-hydroxybutyrate to differentiate between physiologic starvation ketosis (most common), undiagnosed diabetes, or other metabolic emergencies, as urine testing alone is unreliable for diagnosis or management. 1

Immediate Diagnostic Workup

Essential Laboratory Tests

• Measure blood glucose immediately to confirm the patient is truly non-diabetic (glucose <200 mg/dL) and rule out undiagnosed diabetes or euglycemic diabetic ketoacidosis 1, 2
• Obtain blood beta-hydroxybutyrate (bOHB) rather than relying on urine ketones, as standard urine dipsticks only detect acetoacetate and miss bOHB, the predominant ketone body in pathologic ketosis 1, 3
• Check arterial or venous blood gas to assess for metabolic acidosis (pH <7.3, bicarbonate <15 mmol/L) which distinguishes pathologic ketoacidosis from benign starvation ketosis 1, 4
• Calculate anion gap to identify high anion gap metabolic acidosis suggestive of ketoacidosis 4, 5

Critical Clinical Assessment

• Evaluate for symptoms of ketoacidosis: nausea, vomiting, abdominal pain, Kussmaul breathing, altered mental status, or dehydration 1, 4, 6
• Obtain detailed history focusing on: fasting duration, recent illness, alcohol consumption, medication use (especially SGLT2 inhibitors if diabetic status uncertain), pregnancy status in women of childbearing age 1, 3, 2

Differential Diagnosis Algorithm

Most Likely: Physiologic Starvation Ketosis

• Positive urine ketones occur in up to 30% of first morning specimens during fasting or starvation 1, 3
• Blood glucose is normal to mildly elevated (rarely >250 mg/dL) 3
• Acidosis is mild or absent, with serum bicarbonate typically not lower than 18 mEq/L 3
• Management: Increase oral fluid and carbohydrate intake; no specific treatment needed beyond addressing underlying cause 2

Critical to Exclude: Undiagnosed Diabetes with DKA

• New-onset diabetes can present with ketoacidosis as the first manifestation 2, 4
• Euglycemic DKA is possible (glucose <200 mg/dL with ketoacidosis), particularly with SGLT2 inhibitor use, though less likely in truly non-diabetic patients 5, 7, 8
• Diagnostic criteria: Hyperglycemia (or euglycemia with high clinical suspicion), blood bOHB >3 mmol/L, pH <7.3, bicarbonate <15 mmol/L, elevated anion gap 1, 4
• Management: Immediate hospitalization, IV fluids, insulin infusion (0.1 unit/kg/h after 0.15 unit/kg bolus if not hypokalemic), electrolyte replacement 4

Consider: Alcoholic Ketoacidosis

• Presents with positive ketones but hyperglycemia is usually absent 1
• History of alcohol use with recent cessation or binge drinking combined with poor oral intake 1
• Management: IV dextrose-containing fluids, thiamine supplementation, electrolyte repletion 6

Rare: Non-Diabetic Ketoacidosis from Other Causes

• Severe illness, prolonged vomiting, or metabolic disorders can cause ketoacidosis in non-diabetics 6
• Treatment with insulin plus glucose supplementation provides quicker recovery than bicarbonate infusion alone 6

Common Pitfalls to Avoid

Urine Testing Limitations

• Never rely solely on urine ketones for diagnosis or monitoring, as they do not measure bOHB and can underestimate total ketone body concentration 1, 3
• False-positive urine ketones can occur with highly colored urine or sulfhydryl drugs like captopril 1
• False-negative readings occur when test strips are exposed to air or urine is highly acidic 1

Delayed Recognition

• Normal or mildly elevated glucose can mask serious ketoacidosis, delaying recognition of the emergent nature of the problem 5, 7, 8
• Check blood pH and ketones in any ill patient regardless of blood glucose levels 5

Inappropriate Treatment

• Bicarbonate infusion without insulin in ketoacidosis is associated with slower recovery and potential complications including transient coma and seizures 6
• Failure to provide glucose supplementation with insulin when treating non-diabetic ketoacidosis can cause dangerous hypoglycemia 6

Disposition Based on Findings

Outpatient Management (Starvation Ketosis)

• Blood glucose normal, no acidosis (pH >7.35, bicarbonate >18 mEq/L), patient able to tolerate oral intake 3, 2
• Instruct to increase carbohydrate and fluid intake 2
• Follow-up if symptoms persist or worsen 2

Emergency Department/Hospital Admission

• Any metabolic acidosis (pH <7.3, bicarbonate <15 mEq/L) with elevated ketones 4, 6
• Inability to maintain oral hydration due to vomiting or altered mental status 2, 4
• Blood bOHB >3 mmol/L regardless of glucose level 4, 6