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 presence of ketones in the urine (ketonuria) with normal blood glucose levels in a patient taking an SGLT2 inhibitor requires immediate assessment for euglycemic diabetic ketoacidosis (euDKA), which is a medical emergency requiring hospital admission and insulin therapy.

Initial Assessment

1. Evaluate for symptoms of DKA:

   • Nausea, vomiting, abdominal pain
   • Generalized weakness or fatigue
   • Rapid breathing or shortness of breath
   • Confusion or unusual behavior 1, 2

2. Immediate laboratory testing:

   • Serum beta-hydroxybutyrate (bOHB) levels (preferred over nitroprusside-based blood ketone tests) 1
   • Venous blood gas to assess for metabolic acidosis
   • Serum electrolytes and anion gap calculation
   • Complete blood count
   • C-peptide level (to assess endogenous insulin production) 2

Management Algorithm

If symptomatic OR laboratory confirms euDKA (acidosis + elevated bOHB):

1. Immediate hospital admission
2. Treatment protocol:
   • IV fluids (typically dextrose-containing when glucose is normal)
   • IV insulin therapy
   • Electrolyte monitoring and replacement as needed
   • Discontinue SGLT2 inhibitor 1, 3

If asymptomatic with only ketonuria:

1. Temporarily discontinue the SGLT2 inhibitor 2
2. Increase carbohydrate intake (at least 30g per meal) 4
3. Increase fluid intake (non-caloric fluids)
4. Monitor blood glucose and ketones every 3-4 hours 1
5. Consider supplemental insulin doses if ketones persist despite above measures

Risk Factors for euDKA to Assess

• Recent reduction in insulin dose (>20% reduction increases risk) 1
• Low carbohydrate or ketogenic diet 4
• Reduced oral intake or fasting state 5
• Recent illness, surgery, or increased physical stress 6
• Possible undiagnosed late-onset type 1 diabetes or LADA (Latent Autoimmune Diabetes in Adults) 2, 5

Follow-up Plan

1. If euDKA is ruled out and patient is stable:

   • Consider measuring C-peptide levels to assess insulin deficiency risk 2
   • Re-evaluate appropriateness of SGLT2 inhibitor therapy
   • Consider alternative diabetes medications if high risk for euDKA

2. Patient education:

   • Recognize symptoms of euDKA
   • Avoid low-carbohydrate diets while on SGLT2 inhibitors
   • Maintain adequate hydration
   • When to seek immediate medical attention 1, 2

Important Considerations

• SGLT2 inhibitors can precipitate euDKA even with normal blood glucose levels due to increased glucagon/insulin ratio and metabolic shift from glucose to lipid utilization 6
• Approximately 5-10% of adult-onset diabetes is late-onset type 1, and these patients have increased risk of euDKA when taking SGLT2 inhibitors 1
• Blood ketone determinations that rely on nitroprusside reaction should not be used for monitoring treatment of DKA; specific measurement of bOHB is preferred 1

This case highlights the importance of recognizing that SGLT2 inhibitors can cause euDKA without significant hyperglycemia, making diagnosis challenging but critical for proper management.