What is euglycemic diabetic ketoacidosis and how should it be diagnosed and managed?

Euglycemic Diabetic Ketoacidosis

Definition and Diagnostic Criteria

Euglycemic DKA is diabetic ketoacidosis occurring with blood glucose levels <200-250 mg/dL, requiring the same diagnostic criteria as typical DKA except for the glucose threshold: arterial pH <7.3, serum bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and presence of ketonemia or ketonuria. 1, 2, 3

• The absence of marked hyperglycemia creates a diagnostic trap—physicians may overlook DKA when glucose appears "normal," leading to delayed treatment and worse outcomes 2, 4
• Blood pH and ketones must be checked in any ill diabetic patient regardless of glucose levels, as euglycemia masks the underlying metabolic emergency 4

Key Risk Factors and Precipitants

SGLT2 Inhibitors (Most Important Contemporary Cause)

• SGLT2 inhibitors are the leading cause of euglycemic DKA in modern practice and must be discontinued immediately when DKA is suspected 1, 5
• These medications lower renal glucose threshold, preventing the hyperglycemia that typically signals DKA 1
• Risk is 0.6-4.9 events per 1,000 patient-years in type 2 diabetes, with relative risk of 2.46 compared to placebo 1
• SGLT2 inhibitors must be stopped 3-4 days before any planned surgery to prevent perioperative euglycemic DKA 5, 6, 7

Other Major Precipitants

• Pregnancy: Up to 2% of pregnancies with pregestational diabetes develop DKA, often presenting with euglycemia (glucose <200 mg/dL) 1
• Severe carbohydrate restriction or ketogenic diets combined with insulin deficiency 8, 2, 3
• Prolonged fasting, starvation, or reduced caloric intake 2, 3, 4
• Insulin pump failure or abrupt insulin discontinuation 9, 4
• Heavy alcohol consumption and chronic liver disease 2, 3
• Concurrent illness with nausea/vomiting leading to decreased oral intake 1, 4

Diagnostic Approach

Laboratory Workup

• Measure β-hydroxybutyrate (bOHB) in blood—this is the preferred method for diagnosing DKA, as nitroprusside-based tests miss the predominant ketone in DKA 1, 6
• Arterial blood gas showing metabolic acidosis with pH <7.3 5, 2
• Serum bicarbonate <15-18 mEq/L and anion gap >12 mEq/L 5, 2
• Complete metabolic panel, serum osmolality, and electrocardiogram 5, 6
• Blood glucose will be <200-250 mg/dL by definition 1, 2, 3

Critical Diagnostic Pitfall

• Nitroprusside-based urine or blood ketone tests only detect acetoacetate and acetone, not β-hydroxybutyrate, and should not be used for diagnosis or monitoring 1
• During successful DKA treatment, acetoacetate may paradoxically increase as bOHB falls, falsely suggesting worsening ketosis if nitroprusside methods are used 1

Management Protocol

Fluid Resuscitation

• Begin with isotonic saline (0.9% NaCl) or balanced electrolyte solutions at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore intravascular volume 5, 6, 7
• Continue fluid replacement to correct estimated deficits within 24 hours, ensuring serum osmolality changes do not exceed 3 mOsm/kg/hour 6
• Monitor fluid input/output and hemodynamic parameters closely 6, 7

Insulin Therapy (Modified for Euglycemia)

The critical difference in euglycemic DKA management is that dextrose-containing fluids must be started immediately with insulin to prevent hypoglycemia while correcting ketoacidosis. 8, 2, 9

• Start continuous IV regular insulin at 0.1 units/kg/hour 5, 6
• Because glucose is already low, add 5% dextrose to IV fluids from the start of insulin therapy 8, 2, 9
• Some protocols delay insulin until glucose rises above 250 mg/dL with dextrose infusion alone 8
• Target glucose 150-200 mg/dL during treatment while continuing insulin until ketoacidosis resolves 5
• Do not stop insulin when glucose normalizes—continue insulin with dextrose-containing fluids until acidosis and ketosis clear 7, 2

Electrolyte Management

• If initial potassium <3.3 mEq/L, delay insulin therapy and aggressively replace potassium first to prevent life-threatening arrhythmias 5, 6, 7
• Once potassium ≥3.3 mEq/L and urine output confirmed, add 20-40 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) 5, 6
• Target serum potassium 4-5 mEq/L throughout treatment 5
• Bicarbonate is NOT recommended for pH >6.9-7.0, as it provides no benefit and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 5, 6, 7

Monitoring

• Check blood glucose every 1-2 hours 6, 7
• Draw electrolytes, BUN, creatinine, and venous pH every 2-4 hours 5, 6
• Monitor β-hydroxybutyrate levels if available to track ketosis resolution 1, 6
• Continuous cardiac monitoring for arrhythmias due to electrolyte shifts 6, 7

Resolution Criteria

DKA is resolved when ALL of the following are met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L. 5, 6, 7

• Resolution is based on acid-base status and anion gap closure, not glucose normalization 5
• Reduction in blood β-hydroxybutyrate is the most accurate marker of successful treatment 1

Transition to Subcutaneous Insulin

Administer basal insulin (glargine, detemir, or NPH) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 5, 6, 7

• This overlap period is essential—stopping IV insulin without prior subcutaneous basal insulin causes immediate metabolic decompensation 5
• Start multiple-dose regimen with combination of rapid-acting and long-acting insulin once patient can eat 5, 6
• Initial dose approximately 0.5-1.0 units/kg/day for newly diagnosed patients 5

Prevention and Patient Education

For Patients on SGLT2 Inhibitors

• Discontinue SGLT2 inhibitors immediately during any acute illness and do not restart until 3-4 days after metabolic stability is achieved 5, 6, 7
• Check urine or blood ketones during illness even if glucose is normal 1
• Avoid prolonged fasting, very-low-carbohydrate diets, and excessive alcohol intake while on these medications 1

General DKA Prevention

• Never stop basal insulin even when not eating—provide detailed sick-day management instructions 1
• Measure ketones when glucose exceeds 200 mg/dL or during any illness with typical DKA symptoms 1
• Seek immediate medical attention if unable to tolerate oral hydration, altered mental status develops, or symptoms worsen despite home management 1

Discharge Planning

• Identify outpatient diabetes care provider before discharge 5
• Educate on recognition of DKA symptoms, sick-day management, and proper insulin administration 5, 6
• Ensure insulin regimen is prescribed with attention to medication access and affordability 5
• Schedule follow-up within 1-2 weeks 7

Special Populations

Pregnancy

• Pregnant individuals may present with euglycemic DKA and mixed acid-base disturbances, particularly with hyperemesis 1
• Due to significant risk of fetal-maternal harm, pregnant patients at risk should be counseled on DKA signs and seek immediate medical attention if concerned 1

Type 2 Diabetes

• While DKA traditionally occurs in type 1 diabetes, it can occur in type 2 diabetes, especially with SGLT2 inhibitor use 1
• Presence of autoimmunity increases risk in type 2 diabetes patients on SGLT2 inhibitors 1