What should I do for a 45-year-old male with ketonuria (presence of ketones in the urine) and normal Blood Glucose Level (BGL) while taking an SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor?

Management of Ketonuria with Normal Blood Glucose in a Patient on SGLT2 Inhibitor

The presence of ketones in urine with normal blood glucose in a patient taking an SGLT2 inhibitor requires immediate evaluation for euglycemic diabetic ketoacidosis (euDKA) and discontinuation of the SGLT2 inhibitor until the cause is determined. 1

Immediate Assessment

1. Evaluate for euDKA symptoms:

   • Check for nausea, vomiting, abdominal pain, weakness, rapid breathing, or confusion 2, 1
   • Measure vital signs (especially respiratory rate)
   • Assess hydration status

2. Laboratory workup:

   • Blood ketones (specifically β-hydroxybutyrate) - preferred over urine ketones 2
   • Venous blood gas to assess for acidosis
   • Electrolytes and anion gap
   • C-peptide levels to assess endogenous insulin production 1

Management Algorithm

If patient is symptomatic OR has acidosis:

1. Discontinue SGLT2 inhibitor immediately
2. Administer IV fluids (normal saline)
3. Start IV insulin with glucose (dextrose-containing fluids) 3
4. Monitor electrolytes (especially potassium)
5. Admit to hospital for close monitoring

If patient is asymptomatic with normal anion gap:

1. Temporarily discontinue SGLT2 inhibitor

2. Identify and address precipitating factors:

   • Recent low carbohydrate intake or fasting 4
   • Reduced insulin dose
   • Alcohol consumption
   • Acute illness
   • Dehydration

3. Increase carbohydrate intake and ensure adequate hydration

4. Monitor blood ketones (not urine ketones) until resolution 2

Risk Factors for euDKA to Evaluate

• Low C-peptide levels (indicating insulin deficiency) 1
• Possible undiagnosed late-onset type 1 diabetes or LADA 3
• Recent weight loss (as seen in case reports) 3
• Low carbohydrate or ketogenic diet 4
• Recent reduction in insulin dose >20% 2
• Prolonged fasting or reduced oral intake 3

Prevention of Recurrence

1. Consider alternative therapy if patient has risk factors for euDKA:

   • Low C-peptide levels
   • Antibody testing for LADA if clinically suspected 3

2. Patient education if SGLT2 inhibitor is continued:

   • Recognize symptoms of euDKA
   • Avoid prolonged fasting
   • Avoid ketogenic/very low carbohydrate diets 4
   • Monitor ketones during illness
   • When to seek medical attention

3. Coordination with diabetes specialist for complex insulin regimens 2

Important Caveats

• euDKA can occur with normal blood glucose levels (75-250 mg/dL) 3, 5
• Urine ketone tests using nitroprusside reaction do not measure β-hydroxybutyrate (the predominant ketone in DKA) and should not be used for monitoring treatment 2
• SGLT2 inhibitors should be discontinued 3 days before elective procedures 6
• Do not reduce insulin doses by >20% when initiating SGLT2 inhibitors 2, 1

This patient's presentation with ketonuria and normal blood glucose while on an SGLT2 inhibitor should be taken seriously as it may represent early or developing euDKA, a potentially life-threatening condition that requires prompt intervention.