What is diabetic ketoacidosis, its clinical presentation, and recommended acute management?

Diabetic Ketoacidosis (DKA): Overview and Management

Definition and Diagnostic Criteria

DKA is diagnosed when three criteria are simultaneously present: hyperglycemia (typically >250 mg/dL, though euglycemic DKA exists), metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L), and elevated ketones in blood or urine. 1

Core Diagnostic Triad

• Blood glucose typically >250 mg/dL, though euglycemic DKA (glucose <250 mg/dL) occurs with SGLT2 inhibitor use, pregnancy, reduced food intake, alcohol use, or liver failure 1
• Metabolic acidosis with arterial pH <7.30 and serum bicarbonate <18 mEq/L 1
• Elevated ketones positive in serum and urine, with β-hydroxybutyrate measurement preferred over nitroprusside-based tests 1
• Anion gap >10-12 mEq/L (elevated) 1

Severity Classification

• Severe DKA is defined by arterial pH <7.00 and serum bicarbonate <10 mEq/L 1
• Mental status ranges from alert to coma depending on severity, with severe obtundation typically occurring only when pH falls below 7.00 2

Clinical Presentation

Symptom Timeline and Characteristics

• DKA develops rapidly over hours to days, distinguishing it from HHS which evolves over days to weeks 3, 2
• Classic symptoms include polyuria, polydipsia, polyphagia, weight loss, nausea, vomiting, abdominal pain, dehydration, weakness, and altered mental status 1, 4

Physical Examination Findings

• Kussmaul respirations (deep, labored breathing pattern) indicate metabolic acidosis 1
• Poor skin turgor from dehydration 1
• Tachycardia and hypotension from volume depletion 1
• Fruity (acetone) breath odor 2
• Normothermia or hypothermia may be present even with underlying infection; hypothermia is a poor prognostic sign 1
• Altered mental status ranging from full alertness to profound lethargy, though patients are usually alert in DKA compared to HHS 3, 2

Essential Laboratory Evaluation

Initial Diagnostic Workup

Obtain immediately upon suspicion 1:

• Plasma glucose to confirm hyperglycemia
• Serum electrolytes with calculated anion gap
• Arterial blood gases to document pH and assess acidosis severity
• Serum ketones, preferably β-hydroxybutyrate (not nitroprusside-based tests, which miss β-hydroxybutyrate, the predominant ketone in DKA) 1
• Blood urea nitrogen and creatinine to assess renal function and dehydration
• Urinalysis with urine ketones
• Complete blood count with differential
• Electrocardiogram to identify cardiac complications
• HbA1c to distinguish acute decompensation from chronic poor control

Additional Testing When Indicated

• Blood and urine cultures if infection suspected (most common precipitant) 1
• Chest radiography if pneumonia suspected 1
• Amylase, lipase if pancreatitis considered 4
• Troponin, creatine kinase if myocardial infarction suspected 4

Common Precipitating Factors

Most Frequent Triggers 1, 5

• Infection (30-50% of cases)—urinary tract infection and pneumonia most common
• New-onset type 1 diabetes or first presentation
• Insulin omission or inadequate insulin dosing
• Myocardial infarction
• Cerebrovascular accident (stroke)
• Medications: corticosteroids, thiazides, sympathomimetic agents, SGLT2 inhibitors
• Alcohol abuse
• Pancreatitis (less common)
• Trauma or surgery

High-Risk Populations 3

• Type 1 diabetes or absolute insulin deficiency
• Younger age
• Prior history of hyperglycemic or hypoglycemic crises
• Presence of other diabetes complications or chronic health conditions
• Behavioral health conditions (depression, bipolar disorder, eating disorders)
• Alcohol and/or substance use
• High A1C level
• Social determinants of health barriers

Acute Management Protocol

Fluid Resuscitation

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour to restore circulating volume 2
• Average total body water deficit in DKA is approximately 6 liters (compared to 9 liters in HHS) 2
• Add dextrose (D5W) when glucose falls to 200-250 mg/dL while continuing insulin to clear ketones 2

Insulin Therapy

• Begin insulin immediately after initial fluid bolus: 0.1 unit/kg IV bolus followed by continuous infusion of 0.1 unit/kg/h 2
• Target glucose reduction of 50-75 mg/dL/h 6
• Do not stop insulin until ketones clear and acidosis resolves, even if glucose normalizes—this is when dextrose is added 2
• Resolution marker is reduction in blood β-hydroxybutyrate or resolution of acidosis, not glucose normalization 1

Potassium Replacement (Critical)

• Total body potassium deficit in DKA is 3-5 mEq/kg despite normal or elevated initial serum levels 2
• If serum potassium <3.3 mEq/L, hold insulin and give potassium replacement until K⁺ ≥3.3 mEq/L to prevent life-threatening hypokalemia 2
• Once renal function confirmed and K⁺ ≥3.3 mEq/L, add 20-30 mEq/L to IV fluids (2/3 KCl and 1/3 KPO₄) 2
• Insulin drives potassium intracellularly, precipitating dangerous hypokalemia if not anticipated 6

Bicarbonate Use

• Routine bicarbonate therapy is NOT recommended in DKA—randomized studies show no benefit in acidosis resolution or length of stay 2

Monitoring Frequency

• Check blood glucose, electrolytes, and ketones every 2-4 hours until clinically stable 6
• Monitor mental status, vital signs, and urine output continuously 7

Outpatient Management of Mild DKA

When hemodynamically stable, cognitively intact, able to tolerate oral hydration, and able to administer subcutaneous insulin, individuals may treat mild DKA at home with frequent monitoring, noncaloric hydration, and subcutaneous insulin. 3

Criteria for Home Management 3

• Hemodynamically and cognitively intact
• Able to tolerate oral hydration
• Able to administer subcutaneous insulin
• Frequent blood glucose and ketone monitoring available

Immediate Medical Attention Required If 3

• Unable to tolerate oral hydration
• Blood glucose levels do not improve with insulin administration
• Altered mental status develops
• Any signs of worsening illness occur

Prevention Strategies

Patient Education 3

• Measure urine or blood ketones when glucose exceeds 200 mg/dL in the presence of symptoms and potential precipitating factors (illness, missed insulin doses)
• Contact diabetes care team immediately if concerned about or experiencing DKA
• Readily available clinical support helps prevent emergency department visits 3
• Insulin dose adjustments during illness or fasting to prevent DKA occurrence 3

Technology-Based Prevention

• Access to continuous glucose monitoring (CGM) may decrease risk of DKA recurrence 3

Key Distinctions from HHS

Timeline and Presentation 3, 2

• DKA: develops over hours to days, usually alert, Kussmaul respirations present
• HHS: develops over days to a week, change in cognitive state common, no Kussmaul respirations

Laboratory Differences 2

• DKA: glucose typically 250-600 mg/dL, pH <7.30, bicarbonate <15 mEq/L, significant ketones
• HHS: glucose ≥600 mg/dL, pH ≥7.30, bicarbonate ≥15 mEq/L, minimal ketones, osmolality ≥320 mOsm/kg

Mortality 2

• DKA mortality <1% in experienced centers
• HHS mortality approximately 15%, markedly higher than DKA

Critical Pitfalls to Avoid

• Never stop insulin when glucose normalizes—continue until ketones clear and acidosis resolves, adding dextrose as needed 1, 2
• Never give insulin if potassium <3.3 mEq/L—correct potassium first to prevent fatal arrhythmias 2
• Do not rely on nitroprusside-based ketone tests—they miss β-hydroxybutyrate, the predominant ketone 1
• Do not overlook euglycemic DKA in patients on SGLT2 inhibitors, pregnant patients, or those with reduced food intake 1
• Always search for and treat the precipitating cause—infection is most common 1, 5
• Recognize that one-third of hyperglycemic emergencies have hybrid DKA-HHS presentation requiring tailored management 3