• Clinical science

Hyperglycemic crises


Acute hyperglycemia, or high blood glucose, may be either the initial presentation of diabetes mellitus or a complication during the course of a known 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. There are two distinct forms: diabetic ketoacidosis (DKA), typically seen in type 1 diabetes, and hyperosmolar hyperglycemic state (HHS), occurring primarily in type 2 diabetes. In type 1 diabetes, no insulin is available to suppress fat breakdown, and the ketones resulting from subsequent ketogenesis manifest as DKA. This is in contrast to type 2 diabetes, in which patients can still secrete small amounts of insulin to suppress DKA, instead resulting in a hyperglycemic state predominated simply by glucose. The clinical presentation of both DKA and HHS is one of polyuria, polydipsia, nausea and vomiting, volume depletion (e.g., dry oral mucosa, decreased skin turgor), and eventually mental status changes and coma. In patients with altered mental status, fingerstick glucose should always be checked in order to exclude serum glucose abnormalities. Several clinical findings pertaining only to DKA include a fruity odor to the breath, hyperventilation, and abdominal pain. HHS patients, in contrast to those with DKA, will present with more extreme volume depletion. The treatment of both DKA and HHS is primarily IV electrolyte and fluid replacement. Insulin for hyperglycemia may be given with caution and under vigilant monitoring of serum glucose. Other treatment options depend on the severity of symptoms and include bicarbonate and potassium replacement.


DKA, oftentimes precipitated by infection (e.g., pneumonia, urinary tract infection), is commonly the initial manifestation of type 1 diabetes mellitus (approx. 30% of cases)!



Diabetic ketoacidosis (DKA)

Primarily affects patients with type 1 diabetes

Osmotic diuresis and hypovolemia

Insulin deficiency → hyperglycemiahyperosmolalityosmotic diuresis and loss of electrolyteshypovolemia

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

Insulin deficiency → lipolysis↑ free fatty acidshepatic ketone production (ketogenesis) → ketosis bicarbonate consumption (as a buffer) → anion gap metabolic acidosis

DKA is an important cause of anion gap metabolic acidosis with respiratory compensation. (The hyperventilation characteristic of DKA is described in “Clinical findings” below.)

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 therefore 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)


Clinical features

  • Signs and symptoms of both DKA and HHS
    • Polyuria
    • Polydipsia
    • Recent weight loss
    • Nausea and vomiting
    • Signs of volume depletion (i.e., dry mucous membranes, decreased skin turgor), hypotension, circulatory collapse
    • Neurological abnormalities
      • Altered mental status
      • Lethargy
      • Coma
      • Other neurological exam abnormalities such as blurred vision and weakness
  • Signs and symptoms specific to DKA
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 + -
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 type 2 diabetic patients can still possibly produce small amounts of insulin, acute hyperglycemia progresses more slowly and serum glucose is significantly elevated compared with type 1 diabetic patients in DKA (> 600 mg/dL versus > 250 mg/dL)!



  • Initial approach
    • ABCs: airway, breathing, and circulation
    • Mental status check
    • Fingerstick glucose
    • History (taken from family members or friends if need be), including possible precipitating factors
  • Diagnostic tests
  • Additional tests
History Type 1 diabetes Type 2 diabetes
Plasma glucose > 250 mg/dL (>13.9 mmol/L) > 600 mg/dL (> 33.3 mmol/L)
Effective serum osmolality Variable > 320 mosm/kg (> 320 mmol/kg)
Urine and serum ketones Positive Small
Serum bicarbonate < 18 mEq/L (<18 mmol/L) > 18 mEq/L (> 18 mmol/L)
Arterial pH < 7.30 > 7.30
Anion gap > 10 mEq/L (> 10 mmol/L) Variable
Severity of DKA (American Diabetes Association 2009)
Mild Moderate Severe
Arterial pH


7.0 to < 7.2

< 7.0

15–18 mEq/L

10 to < 15 mEq/L

< 10 mEq/L

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

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


Differential diagnoses

All etiologies of 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.

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)

The differential diagnoses listed here are not exhaustive.


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

  • Admission to intensive care unit
    • Patients in mild DKA (see the table in “Diagnostics” above) can be treated in a regular medical ward if careful monitoring is possible there.
    • Assessment and treatment of precipitating factors (e.g., infection)
  • Fluid replacement (and regular monitoring of volume status)
  • Insulin (and hourly serum glucose monitoring until stable)
    • For moderate to severe DKA/HHS (see the table in “Diagnostics” above): low-dose insulin therapy with IV regular insulin; serum glucose should be reduced by a maximum of 50 mg/dL per hour and initially not be allowed to fall below 250 mg/dL
    • In mild DKA (see the table in “Diagnostics” above), treatment with rapid-acting insulin analogs (insulin lispro, aspart, glulisine) in the regular medical ward may be considered.

Treat DKA with normal saline and regular insulin.

  • Bicarbonate (and monitoring of acid-base status)
  • Tight control of serum electrolytes and adjustment if necessary
    • Potassium chloride should be administered at serum potassium levels < 5.3 mEq/L.

Careful monitoring of serum potassium levels is vital during low-dose insulin therapy and while correcting acid-base imbalances!

  • Resolution of DKA/HHS: Once these parameters are within normal limits and oral fluids are tolerated, patients may return to their outpatient insulin dose (or be started on one if they are newly diagnosed diabetics), and discharge may be considered.




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