Diagnostic Approach

The timely diagnosis of Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic Syndrome (HHS) is paramount for effective treatment and to prevent life-threatening complications. Both conditions share overlapping diagnostic criteria but also have unique features that allow for differentiation. In this extensive guide, we’ll delve deeper into the laboratory tests, diagnostic criteria, and clinical considerations essential for the accurate diagnosis of DKA and HHS.

Diagnostic Criteria for DKA

DKA is diagnosed based on the triad of hyperglycemia, ketosis, and acidemia. However, the severity of each of these parameters can vary greatly.

• Hyperglycemia: Blood glucose levels are generally above 250 mg/dL. In some instances, such as euglycemic DKA induced by SGLT-2 inhibitors, this threshold might not be reached. Therefore, relying solely on glucose levels can be misleading.
• Ketosis: Ketones are usually present in both the blood and urine. Blood beta-hydroxybutyrate levels greater than 3 mmol/L are highly indicative of DKA. It’s crucial to measure both urine and blood ketones, especially in cases where SGLT-2 inhibitors have been used, as they can cause euglycemic DKA.
• Acidosis: Acidemia is characterized by a blood pH less than 7.3 and bicarbonate levels below 18 mEq/L. The severity of acidosis can guide treatment decisions and provide prognostic information.

Diagnostic Criteria for HHS

HHS is mainly diagnosed based on severe hyperglycemia and hyperosmolarity, coupled with altered mental status.

• Hyperglycemia: Blood glucose levels are typically extremely elevated, usually above 600 mg/dL. High glucose levels induce an osmotic diuresis that leads to severe dehydration.
• Hyperosmolarity: Effective serum osmolality greater than 320 mOsm/kg is a hallmark feature. This is a critical parameter for distinguishing HHS from DKA.
• Altered Mental Status: Mental status changes in HHS can range from mild confusion to deep coma. Neurologic symptoms can sometimes be the presenting feature in HHS.
• Absence of Severe Ketosis: The absence of significant ketoacidosis helps to distinguish HHS from DKA.

Laboratory Tests and Examinations

• Plasma Glucose: A vital first-line test for identifying hyperglycemia. Both conditions generally have glucose levels far above the normal range.
• Blood Urea Nitrogen (BUN) and Creatinine: Elevated levels indicate reduced renal function, a common feature in both conditions due to osmotic diuresis.
• Serum Ketones: Beta-hydroxybutyrate is the primary ketone body elevated in DKA and should be measured directly for an accurate diagnosis.
• Electrolytes with Anion Gap: An elevated anion gap (>12 mEq/L) is indicative of metabolic acidosis in DKA. Serum potassium may be normal or elevated but does not reflect total body potassium.
• Arterial Blood Gases (ABG): Essential for assessing pH and bicarbonate levels, which are crucial for diagnosing acid-base imbalances.
• Complete Blood Count (CBC): Leukocytosis is common in DKA and HHS but can be misleading as it doesn’t necessarily indicate infection.
• Urinalysis and Urine Ketones: Presence of ketones in urine is a confirmatory sign of DKA but is not reliable for HHS diagnosis.
• ECG: To assess for cardiac arrhythmias, especially in HHS where there is a greater risk of myocardial infarction.
• Chest X-Ray: If pneumonia or other lung infections are suspected as precipitating factors, a chest X-ray becomes necessary.
• Blood, Urine, or Sputum Cultures: In the case of suspected infection, cultures should be taken before initiating antibiotic therapy.

Diagnostic Considerations and Clinical Insights

• Euglycemic DKA: In cases of euglycemic DKA, especially those associated with SGLT2 inhibitors, hyperglycemia might not be present, making diagnosis challenging. Serum ketones and acid-base status become the cornerstone of diagnosis in these instances.
• Serum Osmolality: A critical diagnostic parameter for HHS. Elevated serum osmolality can be indicative of severe dehydration and warrants immediate intervention.
  • Serum Osmolality = 2* (Sodium concentration) + BUN/2.8 + Glucose/18
• Anion Gap: Monitoring the anion gap is vital for assessing the severity of metabolic acidosis in DKA and can be an indicator of treatment progress.
  • Anion Gap: Na+ – (Cl- + HCO3-)
    • Some have argued to use K= in the equation but most US institutions have not adopted this practice
• Mixed Acid-Base Disorders: Both DKA and HHS can present with complex acid-base disorders, such as mixed respiratory and metabolic acidosis or alkalosis. Use of formulas like Winter’s formula can help in the interpretation of these complex scenarios.

Diagnostic Criteria and Laboratory Tests Table