Overview

Diabetic ketoacidosis (DKA) is a severe metabolic complication of diabetes characterized by hyperglycemia (high blood sugar), ketosis (high levels of ketones in the blood), and acidosis (blood becoming too acidic). This condition develops when the body doesn't have enough insulin to allow blood sugar into cells for energy production. As a result, the body begins breaking down fat for fuel, producing ketones as a byproduct.

DKA is most common in people with type 1 diabetes, where the pancreas produces little to no insulin. However, it can also occur in people with type 2 diabetes, particularly during times of severe illness or stress. The condition typically develops over a period of hours to days and can progress rapidly if left untreated.

The hallmark features of DKA include blood glucose levels usually above 250 mg/dL, the presence of ketones in blood or urine, and blood pH below 7.3. This metabolic crisis affects multiple organ systems and can lead to serious complications including cerebral edema, acute kidney injury, and cardiovascular collapse if not promptly recognized and treated. With appropriate medical intervention, most patients recover fully, making early recognition and treatment crucial for optimal outcomes.

Symptoms

The symptoms of diabetic ketoacidosis typically develop rapidly, often within 24 hours. Early recognition of these symptoms is crucial for prompt treatment and prevention of serious complications. The presentation can vary from mild symptoms in the early stages to severe, life-threatening manifestations as the condition progresses.

Early Warning Signs

  • Frequent urination - Often excessive and occurring throughout day and night
  • Excessive thirst - Despite drinking large amounts of fluids
  • High blood sugar levels - Usually above 250 mg/dL
  • Ketones in urine - Detectable with home testing strips

Progressive Symptoms

  • Nausea and vomiting - Often persistent and severe
  • Sharp abdominal pain - May mimic acute abdomen conditions
  • Weakness and fatigue - Progressive and debilitating
  • Decreased appetite - Despite metabolic needs
  • Fruity-scented breath - Due to acetone production
  • Rapid, deep breathing (Kussmaul respirations) - Body's attempt to correct acidosis

Severe Symptoms Requiring Emergency Care

  • Confusion or altered mental state - May progress to coma
  • Sharp chest pain - May indicate cardiac involvement
  • Difficulty breathing or shortness of breath
  • Signs of severe dehydration - Dry mouth, sunken eyes, decreased skin turgor
  • Rapid heart rate and low blood pressure
  • Loss of consciousness

Associated Symptoms

  • Diarrhea - May contribute to dehydration
  • Fluid retention - Paradoxically may occur with treatment
  • Muscle aches and stiffness
  • Blurred vision
  • Dry skin and mucous membranes

Causes

Diabetic ketoacidosis occurs when there is an absolute or relative insulin deficiency combined with increased counter-regulatory hormones (glucagon, cortisol, catecholamines, and growth hormone). This hormonal imbalance leads to increased glucose production, decreased glucose utilization, and enhanced lipolysis with ketone production.

Primary Causes

Insulin Deficiency

  • Missed insulin doses: The most common precipitating factor in known diabetics
  • Insulin pump failure: Mechanical problems, catheter occlusion, or site issues
  • Inadequate insulin dosing: During illness or periods of increased need
  • New-onset type 1 diabetes: DKA may be the presenting feature

Increased Insulin Requirements

  • Infections: Particularly urinary tract infections, pneumonia, and gastroenteritis
  • Acute illness: Myocardial infarction, stroke, pancreatitis
  • Physiologic stress: Surgery, trauma, or severe emotional stress
  • Medications: Corticosteroids, atypical antipsychotics, some diuretics

Pathophysiologic Process

The development of DKA involves several interconnected processes:

  • Hyperglycemia: Lack of insulin prevents glucose uptake by cells, causing blood sugar elevation
  • Lipolysis: Fat breakdown releases free fatty acids
  • Ketogenesis: Liver converts fatty acids to ketone bodies (acetoacetate and β-hydroxybutyrate)
  • Metabolic acidosis: Accumulation of ketones lowers blood pH
  • Osmotic diuresis: High blood glucose causes excessive urination and dehydration
  • Electrolyte imbalances: Loss of sodium, potassium, and other electrolytes

Contributing Factors

  • Poor diabetes management: Inadequate monitoring or adjustment of insulin
  • Substance abuse: Alcohol or drug use may lead to missed insulin doses
  • Eating disorders: Insulin omission for weight control
  • Socioeconomic factors: Limited access to insulin or medical care
  • Psychological factors: Depression, denial, or poor coping mechanisms

Risk Factors

Understanding the risk factors for diabetic ketoacidosis is essential for prevention and early intervention. While anyone with diabetes can develop DKA, certain factors significantly increase the likelihood of this serious complication.

Diabetes-Related Risk Factors

  • Type 1 diabetes: Highest risk due to absolute insulin deficiency
  • Type 2 diabetes with beta-cell failure: Long-standing disease with insulin dependence
  • Previous DKA episodes: History of DKA increases recurrence risk
  • Poor glycemic control: Chronically elevated HbA1c levels
  • New diabetes diagnosis: Particularly in children and young adults

Demographic Factors

  • Age: Children and adolescents with type 1 diabetes at higher risk
  • Socioeconomic status: Limited access to healthcare or insulin
  • Ethnicity: Higher rates in certain ethnic minorities
  • Gender: Slightly higher risk in females, especially during pregnancy

Behavioral and Lifestyle Factors

  • Insulin non-adherence: Deliberate or accidental omission of doses
  • Eating disorders: Particularly in adolescents and young adults
  • Substance abuse: Alcohol or drug use affecting diabetes management
  • Poor self-care behaviors: Inadequate blood glucose monitoring
  • Limited diabetes education: Lack of understanding about DKA prevention

Medical and Physiological Factors

  • Acute illness or infection: Any condition increasing metabolic demands
  • Pregnancy: Increased insulin requirements and hormonal changes
  • Insulin pump use: Risk of mechanical failure or site problems
  • Medications: Corticosteroids, SGLT2 inhibitors, atypical antipsychotics
  • Endocrine disorders: Hyperthyroidism, Cushing's syndrome

Diagnosis

The diagnosis of diabetic ketoacidosis is based on clinical presentation and laboratory findings. Prompt recognition and diagnosis are crucial for initiating appropriate treatment and preventing complications. Healthcare providers use specific criteria to confirm DKA and assess its severity.

Diagnostic Criteria

The diagnosis of DKA requires the presence of all three components:

  • Hyperglycemia: Blood glucose typically >250 mg/dL (13.9 mmol/L)
  • Ketosis: Positive serum or urine ketones
  • Metabolic acidosis: Arterial pH <7.3 or serum bicarbonate <18 mEq/L

Laboratory Tests

Essential Tests

  • Blood glucose: Point-of-care and laboratory measurement
  • Ketones: Serum β-hydroxybutyrate preferred over urine ketones
  • Basic metabolic panel: Electrolytes, BUN, creatinine
  • Arterial blood gas: pH, pCO2, bicarbonate
  • Complete blood count: To assess for infection
  • Urinalysis: Glucose, ketones, signs of infection

Additional Tests

  • Serum osmolality: To assess degree of dehydration
  • Phosphate and magnesium: Often depleted in DKA
  • Cardiac enzymes: If chest pain or ECG abnormalities
  • Blood cultures: If infection suspected
  • Chest X-ray: To rule out pneumonia
  • ECG: For electrolyte abnormalities and cardiac issues

Severity Classification

DKA is classified into three categories based on severity:

  • Mild DKA:
    • pH 7.25-7.30
    • Bicarbonate 15-18 mEq/L
    • Alert mental state
  • Moderate DKA:
    • pH 7.00-7.24
    • Bicarbonate 10-14 mEq/L
    • Alert or drowsy
  • Severe DKA:
    • pH <7.00
    • Bicarbonate <10 mEq/L
    • Stupor or coma

Differential Diagnosis

Conditions that may present similarly include:

Treatment Options

The treatment of diabetic ketoacidosis is a medical emergency requiring intensive monitoring and systematic correction of metabolic abnormalities. The primary goals are to restore fluid volume, correct hyperglycemia and ketoacidosis, replete electrolytes, and identify and treat precipitating factors.

Initial Management

Fluid Resuscitation

Aggressive fluid replacement is the first priority:

  • Initial bolus: 15-20 mL/kg of 0.9% saline in first hour
  • Subsequent fluids: 250-500 mL/hour based on hydration status
  • Fluid choice: Switch to 0.45% saline if corrected sodium is normal or high
  • Dextrose addition: When glucose falls below 200-250 mg/dL

Insulin Therapy

Low-dose insulin protocol is standard:

  • Initial dose: Regular insulin 0.1 unit/kg IV bolus (optional)
  • Continuous infusion: 0.1 unit/kg/hour
  • Adjustment: Increase if glucose doesn't fall by 50-75 mg/dL/hour
  • Transition: Overlap with subcutaneous insulin before stopping infusion

Electrolyte Management

Potassium Replacement

  • If K+ <3.3 mEq/L: Hold insulin, give 20-30 mEq/hour until >3.3
  • If K+ 3.3-5.2 mEq/L: Add 20-30 mEq to each liter of fluid
  • If K+ >5.2 mEq/L: Do not give potassium, monitor every 2 hours

Other Electrolytes

  • Phosphate: Replace if <1.0 mg/dL or with cardiac/respiratory dysfunction
  • Magnesium: Replace if low or with refractory hypokalemia
  • Bicarbonate: Generally not recommended unless pH <6.9

Monitoring and Complications

Monitoring Parameters

  • Hourly glucose and vital signs
  • Electrolytes every 2-4 hours
  • Venous pH or bicarbonate every 2-4 hours
  • Strict intake and output monitoring
  • Neurological assessments

Potential Complications

  • Cerebral edema: Rare but serious, mainly in children
  • Hypokalemia: From insulin therapy and correction of acidosis
  • Hypoglycemia: From excessive insulin
  • Acute kidney injury: From severe dehydration
  • Thrombosis: Due to dehydration and hyperviscosity

Resolution Criteria

DKA is considered resolved when:

  • Blood glucose <200 mg/dL
  • Serum bicarbonate ≥18 mEq/L
  • Venous pH >7.3
  • Anion gap ≤12 mEq/L
  • Patient able to eat and drink

Prevention

Preventing diabetic ketoacidosis is largely achievable through proper diabetes management, patient education, and early recognition of warning signs. Most cases of DKA can be prevented with appropriate self-care behaviors and access to medical care.

Primary Prevention Strategies

  • Never skip insulin doses: Even when ill or not eating
  • Regular blood glucose monitoring: Increase frequency during illness
  • Ketone testing: Check when glucose >250 mg/dL or during illness
  • Sick day management plan: Written instructions for illness management
  • Regular medical follow-up: Routine diabetes care visits

Sick Day Management

Key principles for managing diabetes during illness:

  • Continue taking insulin even if not eating normally
  • Check blood glucose every 2-4 hours
  • Test urine or blood ketones if glucose >250 mg/dL
  • Stay hydrated with sugar-free fluids
  • Contact healthcare provider if ketones are moderate or large
  • Have emergency contact numbers readily available

Patient Education Topics

  • Insulin administration: Proper technique and storage
  • Pump management: Troubleshooting and backup plans
  • Recognition of symptoms: Early warning signs of DKA
  • Action plans: What to do when blood glucose is high
  • Lifestyle factors: Diet, exercise, and stress management

Healthcare System Interventions

  • 24/7 access to diabetes care team
  • Affordable insulin and supplies
  • Regular screening for at-risk patients
  • Transitional care programs for adolescents
  • Mental health support for diabetes management

When to See a Doctor

Diabetic ketoacidosis is a medical emergency that requires immediate hospital treatment. Recognizing when to seek medical care can be life-saving. People with diabetes should be familiar with warning signs and have a clear action plan.

Seek Emergency Medical Care Immediately If:

  • Blood glucose remains above 300 mg/dL despite insulin
  • Moderate or large ketones in urine or blood
  • Persistent vomiting (unable to keep fluids down)
  • Severe abdominal pain
  • Rapid, deep breathing or shortness of breath
  • Fruity breath odor
  • Confusion or difficulty concentrating
  • Signs of severe dehydration

Contact Your Healthcare Provider If:

  • Blood glucose consistently above 250 mg/dL
  • Trace or small ketones present
  • Feeling ill but able to keep fluids down
  • Uncertainty about insulin adjustments during illness
  • Fever lasting more than 24 hours
  • Diarrhea or vomiting for more than 6 hours

What to Tell Healthcare Providers

When seeking medical care, provide the following information:

  • Current blood glucose and ketone levels
  • Recent insulin doses and timing
  • Symptoms and duration
  • Any recent illness or stress
  • Current medications
  • Fluid intake and urination frequency

Related Conditions

Several conditions are related to or may be confused with diabetic ketoacidosis. Understanding these relationships helps in proper diagnosis, treatment, and management of diabetes complications.

Other Acute Diabetes Complications

Underlying Conditions

Precipitating Conditions

Other Ketotic States

Frequently Asked Questions

Can people with type 2 diabetes develop DKA?

Yes, although less common than in type 1 diabetes, people with type 2 diabetes can develop DKA, especially during severe illness, with SGLT2 inhibitor use, or when pancreatic insulin production is significantly impaired. Some people initially diagnosed with type 2 diabetes may actually have late-onset type 1 diabetes.

How quickly does DKA develop?

DKA typically develops over 24-48 hours, but can occur more rapidly in some cases, particularly with insulin pump failure or during severe illness. Early symptoms like increased thirst and urination may be present for several days before more serious symptoms develop.

Can DKA be managed at home?

No, DKA is a medical emergency that requires hospital treatment. While early ketosis might be managed with increased insulin and fluids under medical guidance, established DKA needs intravenous fluids, insulin, and careful monitoring that can only be provided in a hospital setting.

What is euglycemic DKA?

Euglycemic DKA is a form of diabetic ketoacidosis where blood glucose levels are relatively normal (<250 mg/dL) despite the presence of ketoacidosis. This can occur with SGLT2 inhibitor use, pregnancy, prolonged fasting, or alcohol use in people with diabetes.

How long does recovery from DKA take?

Most patients recover from DKA within 24-48 hours with appropriate treatment. However, full recovery including normalization of all metabolic parameters and resolution of symptoms may take several days. The underlying precipitating factor may require additional treatment time.

Can DKA cause permanent damage?

With prompt treatment, most people recover completely from DKA without permanent damage. However, severe or prolonged DKA can lead to complications such as cerebral edema (brain swelling), acute kidney injury, or rarely, death. This emphasizes the importance of prevention and early treatment.

How can I prevent DKA during illness?

Continue taking insulin even if not eating normally, check blood glucose every 2-4 hours, test for ketones if glucose is above 250 mg/dL, stay hydrated, and contact your healthcare provider early. Having a written sick day management plan is essential for all people with insulin-dependent diabetes.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of medical conditions. If you suspect DKA, seek emergency medical care immediately.

References

  1. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343.
  2. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Supplement_1).
  3. Dhatariya KK, et al. Diabetic ketoacidosis. Nature Reviews Disease Primers. 2020;6(1):40.
  4. Savage MW, et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabetic Medicine. 2011;28(5):508-515.
  5. Wolfsdorf JI, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatric Diabetes. 2018;19(Suppl 27):155-177.