What is concerning about elevated ketone levels in diabetes?

Elevated Ketone Levels in Diabetes: Serious Complications and Management

Elevated ketone levels in diabetes are concerning primarily because they can lead to diabetic ketoacidosis (DKA), a life-threatening condition that can cause significant morbidity and mortality if not promptly identified and treated. 1

Understanding Ketones and Their Dangers

Ketones are produced by the liver when there is insufficient insulin to allow glucose utilization, causing the body to break down fat for energy. The three main ketone bodies are:

• Beta-hydroxybutyrate (BHB) - most abundant in pathological states
• Acetoacetate
• Acetone

Why High Ketones Are Dangerous

1. Metabolic Acidosis: High ketone levels lead to metabolic acidosis, which disrupts normal cellular function throughout the body 2

2. Risk of Diabetic Ketoacidosis (DKA): DKA is diagnosed by:

   • Elevated blood glucose (typically >250 mg/dL)
   • Metabolic acidosis (pH <7.3, serum bicarbonate <15 mEq/L)
   • Ketonemia with BHB ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults 2

3. Severity Classification:

   • Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L
   • Moderate DKA: pH 7.00-7.24, bicarbonate 10-<15 mEq/L
   • Severe DKA: pH <7.00, bicarbonate <10 mEq/L 2

Clinical Manifestations of High Ketones

When ketones rise to dangerous levels, patients may experience:

• Nausea and vomiting
• Abdominal pain
• Kussmaul respiration (deep, rapid breathing)
• Polyuria, polydipsia, weight loss, and dehydration
• Altered mental status (especially in hyperglycemic hyperosmolar state)
• Acetone breath 1, 3

High-Risk Populations

Certain groups are at increased risk for developing elevated ketones and DKA:

• Type 1 diabetes patients (primary risk group)
• Patients with absolute insulin deficiency
• Younger individuals
• Those with prior history of hyperglycemic crises
• Patients with other diabetes complications
• Those with behavioral health conditions
• Alcohol and substance users
• Patients with high A1C levels 1

Special Considerations

SGLT2 Inhibitors and Euglycemic DKA

Patients taking SGLT2 inhibitors are at increased risk of developing DKA, including euglycemic DKA (DKA with blood glucose <200 mg/dL). Risk factors include:

• Very-low-carbohydrate diets
• Prolonged fasting
• Dehydration
• Excessive alcohol intake
• Presence of autoimmunity 1, 2

Pregnancy

Pregnant women with diabetes require special attention:

• Up to 2% of pregnancies with pregestational diabetes (mostly type 1) are complicated by DKA
• Pregnant women may present with euglycemic DKA
• Diagnosis may be hindered by mixed acid-base disturbances, especially with hyperemesis
• Significant risk of feto-maternal harm exists 1, 2

Monitoring and Prevention

To prevent serious complications from elevated ketones:

1. Regular ketone monitoring for high-risk individuals:

   • During illness
   • With unexplained hyperglycemia
   • When using SGLT2 inhibitors (regardless of glucose levels)
   • During pregnancy with diabetes 2

2. Preferred monitoring method:

   • Blood β-hydroxybutyrate testing is preferred over urine ketone testing
   • BHB is the predominant ketone in DKA
   • Nitroprusside-based urine dipsticks only detect acetoacetate, not BHB 2

3. Never discontinue basal insulin, even when not eating 1

4. Immediate action when ketones are elevated:

   • Frequent blood glucose and ketone monitoring
   • Non-caloric hydration
   • Subcutaneous insulin administration for mild cases
   • Seek immediate medical attention if unable to tolerate oral hydration, blood glucose doesn't improve with insulin, altered mental status develops, or worsening illness occurs 1

Resolution of DKA

DKA resolution is defined by:

• BHB value <1.5 mmol/L
• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH ≥7.3 2

Prevention Strategies

1. Maintain insulin therapy - inadequate dosing or discontinuation can lead to hyperglycemia and DKA 3

2. Patient education on sick day management and ketone monitoring

3. Provide detailed instructions on insulin dose adjustments during illness or fasting 1

4. Encourage immediate contact with diabetes care team when concerned about DKA 1

5. Consider continuous ketone monitoring for high-risk patients, especially those with type 1 diabetes, pregnancy, on SGLT2 inhibitors, with recurrent DKA, or on low carbohydrate diets 4

By understanding the serious implications of elevated ketones and implementing proper monitoring and management strategies, the risk of developing life-threatening DKA can be significantly reduced.