Coexistence of Low Blood Glucose and High Ketones
Yes, hypoglycemia can coexist with high ketone levels in several clinical scenarios, most notably in euglycemic diabetic ketoacidosis (euDKA), starvation ketosis, and certain metabolic disorders.
Clinical Scenarios Where Low Glucose and High Ketones Coexist
1. Euglycemic Diabetic Ketoacidosis (euDKA)
- Most commonly seen in patients taking SGLT-2 inhibitors 1
- Blood glucose levels may be <200 mg/dL (sometimes even normal) despite significant ketosis
- Mechanism: SGLT-2 inhibitors cause glycosuria while maintaining ketogenesis, leading to ketoacidosis without marked hyperglycemia
- Requires immediate treatment with glucose-containing IV fluids and insulin 1
2. Starvation Ketosis
- Occurs during prolonged fasting or severe caloric restriction
- As glucose levels fall, the body shifts to fat metabolism, producing ketones
- Unlike DKA, acidosis is typically mild or absent
- Blood glucose is low while ketones are elevated
3. Ketotic Hypoglycemia in Children
- Most common cause of hypoglycemia in children 1-5 years old 2
- Characterized by low blood glucose with elevated ketone bodies
- Often occurs after overnight fasting or during illness
- Symptoms may mimic other common conditions (psychiatric disorders, migraine, gastrointestinal issues) 2
4. Metabolic Disorders
- Certain inborn errors of metabolism can present with hypoketotic hypoglycemia
- Example: Citrin deficiency may present with hypoglycemia and insufficient ketosis 3
- These conditions often involve impaired fatty acid oxidation or other metabolic pathways
Clinical Implications and Management
Diagnostic Considerations
- When encountering low blood glucose with high ketones, consider:
- Medication effects (especially SGLT-2 inhibitors)
- Duration of fasting
- Underlying metabolic disorders
- Insulin availability and recent administration
- Specific measurement of β-hydroxybutyrate (bOHB) in blood is preferred over nitroprusside-based tests that only detect acetoacetate 4
Management Approach
- For euDKA: Administer glucose-containing IV fluids and insulin 1
- For ketotic hypoglycemia in children: Prompt IV glucose administration 2
- For starvation ketosis: Carbohydrate refeeding with monitoring
- Always address the underlying cause
Monitoring Considerations
- Blood ketone determinations that measure bOHB specifically are useful for diagnosis and monitoring 4
- Nitroprusside-based tests should not be used for monitoring treatment as they don't measure bOHB, the predominant ketone in DKA 4
Prevention Strategies
For Diabetic Patients
- Education about ketone monitoring during illness or when blood glucose is persistently elevated 5
- Recognition of early warning signs of DKA 5
- Never omitting insulin doses 5
- Understanding that hypoglycemia may increase risk of harm to self or others 4
For Children with Ketotic Hypoglycemia
- Supply frequent snacks containing complex carbohydrates ("slow sugars"), particularly at bedtime 2
- Educate caregivers about recognition and management of hypoglycemic episodes
Important Caveats
- The nitroprusside test only detects acetoacetate in blood and urine, not β-hydroxybutyrate, which is the predominant ketone body in DKA 6
- In acute DKA, the ketone body ratio (3HB:AcAc) can rise from normal (1:1) to as high as 10:1 6
- During treatment, β-hydroxybutyrate levels commonly decrease before acetoacetate levels 6
- Older adults (≥80 years) are at higher risk for hypoglycemia-related admissions 5
Understanding the coexistence of low blood glucose and high ketones is essential for proper diagnosis and management of these potentially serious metabolic disturbances.