Hyperglycemic crises

Last updated: May 9, 2022

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Acute hyperglycemia, or high blood glucose, can be either the initial presentation of diabetes mellitus or a complication arising during the course of another disease. Inadequate insulin replacement (e.g., noncompliance with treatment) or increased insulin demand (e.g., during times of acute illness, surgery, or stress) may lead to acute hyperglycemia. In diabetic ketoacidosis (DKA), which is more common in patients with type 1 diabetes, no insulin is available to suppress lipolysis, resulting in ketone formation and acidosis. In a hyperosmolar hyperglycemic state (HHS), which is more common in patients with type 2 diabetes, there is still some insulin available, so there is minimal or no ketone formation. Clinical features of both DKA and HHS include polyuria, polydipsia, nausea and vomiting, volume depletion (e.g., dry oral mucosa, decreased skin turgor), and eventually mental status changes and coma. Features unique to DKA include a fruity odor to the breath, hyperventilation, and abdominal pain. Patients with HHS typically present with more extreme volume depletion than those with DKA. The mainstay of treatment for both DKA and HHS consists primarily of IV fluid resuscitation, electrolyte repletion, and insulin therapy.

Comparison of DKA and HHS
Diabetic ketoacidosis Hyperosmolar hyperglycemic state
  • Absent
  • Present


  • Present
  • Absent






The most important findings of diabetic ketoacidosis (DKA) are: Delirium/psychosis, Dehydration, Kussmaul respirations, Abdominal pain/nausea/vomiting, fruity (Acetone) breath odor.

DKA, often precipitated by infection (e.g., pneumonia, urinary tract infection), is a common initial manifestation of type 1 diabetes mellitus (∼ 30% of cases).

Diabetic ketoacidosis (DKA)

DKA primarily affects patients with type 1 diabetes.

Osmotic diuresis and hypovolemia

Hypovolemia resulting from DKA can lead to acute kidney injury (AKI) due to decreased renal blood flow! Hypovolemic shock may also develop.

Metabolic acidosis with increased anion gap

DKA is an important cause of anion gap metabolic acidosis with respiratory compensation.

Intracellular potassium deficit

  • As a result of hyperglycemic hyperosmolality, potassium shifts along with water from inside cells to the extracellular space and is lost in the urine.
  • Insulin normally promotes cellular potassium uptake but is absent in DKA, compounding the problem.
  • A total body potassium deficit develops in the body, although serum potassium may be normal or even paradoxically elevated.
  • Insulin deficiency → hyperosmolality K+ shift out of cells + lack of insulin to promote K+ uptake → intracellular K+depleted → total body K+ deficit despite normal or even elevated serum K+

There is a total body potassium deficit in DKA. This becomes important during treatment, when insulin replacement leads to rapid potassium uptake by depleted cells and patients may require potassium replacement.

Hyperosmolar hyperglycemic state (HHS)

Signs and symptoms of both DKA and HHS

Specific findings in DKA [1]

  • Rapid onset (< 24 h) in contrast to HHS
  • Abdominal pain
  • Fruity odor on the breath (from exhaled acetone)
  • Hyperventilation: long, deep breaths (Kussmaul respirations)

Comparison: DKA vs. HHS

Clinical findings of DKA versus HHS
Diabetes Type 1 Type 2
History of severe stress, illness, hospitalization + +
Polyuria, polydipsia + +
Nausea, vomiting + +/-
Dehydration + ++ (Profound)
Altered mental status Possible Possible
Hyperventilation or Kussmaul breathing + -
Fruity breath + -
Severe abdominal pain + -
Onset Rapid (< 24 h) Insidious (days)

Known diabetics who present with nausea and vomiting should be immediately assessed for DKA/HHS. Because patients with type 2 diabetes can still produce small amounts of insulin in some cases, acute hyperglycemia progresses more slowly and serum glucose is significantly elevated compared with patients with type 1 diabetes in DKA (> 600 mg/dL in HHS versus > 250 mg/dL in DKA).

Approach [2][3]

Overview of laboratory findings in hyperglycemic crises [2]

Diagnostic criteria for DKA and HHS
Laboratory test DKA HHS
BMP Glucose
  • < 600 mg/dL (< 33.3 mmol/L)
  • About 10% of patients with DKA will be euglycemic (e.g., glucose ≤ 250 mg/dL) [2]
  • > 600 mg/dL (> 33.3 mmol/L)
  • < 18 mEq/L (< 18 mmol/L)
  • > 18 mEq/L (> 18 mmol/L)
Anion gap
Serum β-hydroxybutyrate
  • Elevated
  • Normal
Blood gas
  • pH ≤ 7.30
  • pH > 7.30
Serum osmolality
  • Normal or mildly elevated
  • Elevated > 320 mosm/kg (> 320 mmol/kg)

DKA is the diagnosis in patients with type 1 diabetes who have hyperglycemia, ketonuria, and high anion gap metabolic acidosis with decreased bicarbonate!

HHS is the diagnosis in patients with type 2 diabetes who have hyperglycemia and hyperosmolality!

Ketone levels should be ordered in all patients with high anion gap metabolic acidosis to evaluate for euglycemic DKA.

Electrolytes and renal function [2][3]

Additional diagnostic workup [2][3][7]

Infection, myocardial infarction, and pancreatitis should be ruled out in all patients presenting with a hyperglycemic crisis.

Pregnancy and SGLT2-inhibitors can cause euglycemic DKA (i.e., high anion gap metabolic acidosis with normal or near-normal glucose). [8][10].

Severity of DKA [2]

Arterial pH Serum bicarbonate Anion gap Mental status
Mild > 7.24 15–18 mEq/L > 10 mEq/L Alert
Moderate 7.0–7.24 10–15 mEq/L > 12 mEq/L Alert or drowsy
Severe < 7.0 < 10 mEq/L > 12 mEq/L Stuporous


Initially treat DKA with normal saline and short-acting (regular) insulin.

Fluid resuscitation [2][7][11]

Electrolyte repletion [2]

Serum K+ Recommended dose [12]
< 3.3 mEq/L

3.3–5.2 mEq/L

> 5.2 mEq/L

  • No repletion recommended

It is critical that potassium levels are confirmed to be > 3.3 mEq/L before administering insulin, as insulin will lower serum potassium and potentially cause severe hypokalemia.

Insulin [2][11][13]

  • The administration of insulin is essential in halting lipolysis and ketoacidosis in patients with DKA.
  • Recommended regimens [2]
    • IV regular insulin bolus , followed by continuous regular insulin IV infusion
    • Or regular insulin continuous IV infusion without a bolus
    • Both options listed are valid approaches with advantages and disadvantages. When in doubt, follow hospital standards.
  • Check glucose level hourly and titrate as needed.
  • The goal is to decrease blood glucose levels by 10% per hour (∼ 50–75 mg/dL/hour).
  • Treatment with subcutaneous rapid-acting insulin analogues on a regular medical ward may be considered in cases of mild DKA.

Acid-base status [2]

Monitoring [2][11] [14]

  • Admission to the ICU or closely monitored setting [2]
  • Consider endocrine consult.
  • NPO status in patients with high anion gap metabolic acidosis on insulin infusion
  • Hourly monitoring of vitals and mental status and hydration status
  • POC glucose every 1–2 hours until blood glucose < 250 mg/dL and hourly blood glucose readings are stable for at least 3 hours; then decrease monitoring to every 2–4 hours
  • Serum osmolality every 1–4 hours
  • Blood gas and BMP with electrolytes every 2–4 hours

Monitoring of volume status, serum glucose, serum electrolytes, and acid-base status at regular intervals is essential.

Resolution and transition to subcutaneous insulin [2]

Criteria for the resolution of hyperglycemic crises [2][3]
  • Glucose < 200 mg/dL
  • PLUS at least two of the following:
  • Criteria for transitioning to subcutaneous insulin:
    • Resolution of hyperglycemic crisis
    • Precipitating factor identified and treated
    • Patient tolerating oral nutrition and eating consistently
  • Procedure for transitioning to subcutaneous insulin:
Differential diagnosis of DKA/HHS and hypoglycemia
DKA/HHS Hypoglycemia
Onset Hours to days Minutes
Appetite Unchanged
Thirst ∅ (unchanged)
Muscle tone ↑ (tremor)
Skin turgor ↓ (dry skin) ↑ (moist skin)
Respirations ↑ (Kussmaul respirations with DKA) Unchanged

All other etiologies that may cause altered mental status must be considered in the differential diagnosis of DKA/HHS. Intoxication and other endocrine disorders, as well as gastroenteritis, myocardial infarction, pancreatitis, and other causes of high anion gap metabolic acidosis, should all be excluded.

We list the most important complications. The selection is not exhaustive.

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