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 in a Patient on SGLT2 Inhibitor with Normal Blood Glucose

The patient should be immediately evaluated for euglycemic diabetic ketoacidosis (euDKA), a potentially life-threatening complication of SGLT2 inhibitor therapy, despite having normal blood glucose levels. 1

Immediate Assessment

1. Clinical evaluation for euDKA symptoms:

   • Check for nausea, vomiting, abdominal pain, generalized weakness
   • Assess for rapid breathing or shortness of breath
   • Look for confusion or unusual behavior

2. Laboratory workup:

   • Venous blood gas to assess pH and bicarbonate
   • Serum ketones (specifically β-hydroxybutyrate)
   • Complete metabolic panel to calculate anion gap
   • C-peptide level to assess endogenous insulin production

Risk Assessment

EuDKA in patients on SGLT2 inhibitors can occur with normal blood glucose levels, making it easily missed. Several risk factors increase likelihood:

• Low C-peptide levels (indicating insulin deficiency)
• Recent carbohydrate restriction or fasting
• Reduced oral intake or illness
• Possible undiagnosed late-onset type 1 diabetes (LADA) (5-10% of adult-onset diabetes) 2

Management Algorithm

If Signs of Acidosis Present (pH <7.3, bicarbonate <18 mEq/L, elevated anion gap):

1. Immediately discontinue the SGLT2 inhibitor
2. Administer IV fluids with dextrose (even with normal BGL)
3. Start insulin infusion to suppress ketogenesis
4. Monitor electrolytes and replace as needed
5. Treat any precipitating factors (infection, dehydration)

If No Signs of Acidosis:

1. Temporarily discontinue SGLT2 inhibitor until full evaluation completed

2. Assess for precipitating factors:

   • Recent dietary changes (low carbohydrate diet)
   • Reduced oral intake
   • Concurrent illness
   • Excessive alcohol consumption

3. Monitor closely with:

   • Blood ketone measurements (β-hydroxybutyrate preferred over urine ketones) 2
   • Repeat metabolic panel in 12-24 hours
   • Patient education about warning symptoms

Prevention and Follow-up

1. Evaluate for undiagnosed type 1 diabetes:

   • Check C-peptide levels
   • Consider autoantibody testing (GAD65, ZnT8)

2. Patient education:

   • Recognize symptoms of euDKA
   • Understand when to seek medical attention
   • Avoid low carbohydrate diets while on SGLT2 inhibitors 3
   • Maintain adequate hydration and carbohydrate intake

3. Medication adjustments:

   • Consider alternative diabetes medications if high risk for euDKA
   • If continuing SGLT2 inhibitor, ensure close monitoring

Important Caveats

• Do not rely on urine ketone determinations alone for diagnosis or monitoring of DKA 2
• Normal blood glucose does not rule out DKA in patients on SGLT2 inhibitors 4
• Blood ketone determinations that measure β-hydroxybutyrate specifically are preferred for diagnosis and monitoring 2
• Patients with complex insulin regimens should have SGLT2 inhibitors managed in collaboration with diabetes specialists 2

By following this approach, you can effectively manage this potentially serious complication while ensuring patient safety and appropriate follow-up care.