Hyperglycemic crises can be the initial presentation of diabetes mellitus or complications due to other diseases. Inadequate insulin replacement (e.g., due to poor adherence) 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. DKA typically has an acute onset (e.g., within hours) while HHS usually develops insidiously (e.g., within days) and manifests with more extreme volume depletion. The mainstay of treatment for both DKA and HHS consists of IV fluid resuscitation, electrolyte repletion, and insulin therapy.
|Comparison of DKA and HHS|
|Diabetic ketoacidosis||Hyperosmolar hyperglycemic state|
|Insulin|| || |
| || |
- Lack of or insufficient insulin replacement therapy
- Increased insulin demand
- normally elevates cellular uptake of glucose from the blood.
- In the insulin-deficient state of DKA, hyperglycemia occurs.
- Hyperglycemia, in turn, leads to progressive volume depletion via osmotic diuresis.
- Insulin deficiency → hyperglycemia → hyperosmolality → osmotic diuresis and loss of electrolytes → hypovolemia
Metabolic acidosis with increased anion gap
- Insulin deficiency also increases fat breakdown (lipolysis).
- Metabolic acidosis develops as the free fatty acids generated by lipolysis become ketones, two of which are acidic (acetoacetic acid and beta-hydroxybutyric acid).
- Serum bicarbonate is consumed as a buffer for the acidic ketones. Metabolic acidosis with an elevated anion gap is therefore characteristic of DKA.
- Insulin deficiency → ↑ lipolysis → ↑ free fatty acids → hepatic ketone production (ketogenesis) → ketosis → bicarbonate consumption (as a buffer) → metabolic acidosis
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.
- Primarily affects patients with type 2 diabetes
- The pathophysiology of HHS is similar to that of DKA.
- However, in HHS, there are still small amounts of insulin being secreted by the pancreas, and this is sufficient to prevent DKA by suppressing lipolysis and, in turn, ketogenesis.
- HHS is characterized by symptoms of marked dehydration (and loss of electrolytes) due to the predominating hyperglycemia and osmotic diuresis.
- Recent weight loss
- Nausea and vomiting
- Signs of significant dehydration
- Neurological abnormalities
Specific findings in DKA 
- Rapid onset (< 24 h) in contrast to HHS
- Abdominal pain
- Fruity odor on the breath (from exhaled acetone)
- Hyperventilation: long, deep breaths (Kussmaul respirations)
|Clinical findings of DKA versus HHS|
|Diabetes||Type 1||Type 2|
|History of severe stress, illness, hospitalization||+||+|
|Altered mental status||Possible||Possible|
|Hyperventilation or Kussmaul breathing||+||-|
|Severe abdominal pain||+||-|
|Onset||Rapid (< 24 h)||Insidious (days)|
- Check serum glucose to confirm hyperglycemia.
- Check BMP for serum bicarbonate, anion gap, electrolytes, and renal function.
- Check for the presence of ketones.
- Check blood gas analysis for pH. 
- Diagnostic workup to evaluate the underlying cause: HbA1c, CBC, ECG, infectious workup
Overview of laboratory findings in hyperglycemic crises 
- DKA: hyperglycemia, high anion gap metabolic acidosis, ketonuria/ketonemia
- HHS: hyperglycemia, hyperosmolality, and dehydration without ketonuria
|Diagnostic criteria for DKA and HHS|
|Bicarbonate|| || |
|Anion gap|| || |
|Serum β-hydroxybutyrate|| || |
|Blood gas|| || |
|Serum osmolality|| || |
Electrolytes and renal function 
- Potassium in DKA: normal or elevated (despite a total body deficit)
- Magnesium levels are typically low.
- Phosphorus levels may be elevated despite a total body deficit.
- BUN and creatinine are often elevated. 
Additional diagnostic workup 
Additional diagnostics are indicated depending on suspected precipitating causes and differential diagnoses.
- Urine pregnancy test 
- CT head
- Toxicology screen
- , e.g.:
- 12-lead ECG , e.g.,
- , e.g.:
Severity of DKA 
- Initial steps
- isotonic saline: initially with (0.9% NaCl)
- potassium level < 5.3 mEq/L : for
- short-acting insulin: initiate once potassium level is > 3.3 mEq/L
- IV sodium bicarbonate: only for severe refractory metabolic acidosis 
- Identify and treat precipitating causes (e.g., sepsis).
- Consider endocrine consult and admission to the ICU.
- Hourly 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.
Discharge may be considered for patients with mild DKA and all of the following:
- Resolved anion gap acidosis
- No concerning precipitating cause
- Toleration of oral hydration and nutrition
- Ability to adhere to discharge instructions, including outpatient follow-up
Fluid and electrolyte management
Fluid resuscitation 
- First hour: isotonic saline solution (0.9% sodium chloride) at 15–20 mL/kg/hour (∼ 1000–1500 mL bolus) 
- Next 24–48 hours: Adjust IV fluid rate and composition according to CVP, urine output, blood glucose, and corrected sodium levels.
- Switch to a solution containing dextrose (e.g., D5NS) when glucose falls to ∼ 200 mg/dL (DKA) or 300 mg/dL (HHS).
- Potassium levels must be ≥ 3.3 mEq/L before insulin therapy is initiated
- If potassium level is < 3.3 mEq/L, potassium should be repleted and rechecked prior to giving any insulin.
- If potassium level is < 5.3 mEq/L, the patient will likely require potassium repletion once insulin therapy is started
- Maintain serum potassium between 4–5 mEq/L.
- Use extreme caution with potassium repletion in anuric patients.
- Monitor potassium levels every 2 hours while administering insulin infusion.
- See also repletion regimens for hypokalemia.
|Serum K+||Recommended dose |
|< 3.3 mEq/L|
> 5.2 mEq/L
- Phosphorus: See repletion regimens for hypophosphatemia.
- Magnesium: See repletion regimens for hypomagnesemia.
Acid-base status 
General principles 
- The administration of insulin is essential in halting lipolysis and ketoacidosis in patients with DKA.
- Recommended regimens 
- The initial goal is to decrease blood glucose levels by 10% per hour (∼ 50–75 mg/dL/hour).
- Check glucose level hourly and titrate as needed.
- In patients requiring ongoing insulin infusion:
Resolution and transition to subcutaneous insulin 
|Criteria for the resolution of hyperglycemic crises |
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:
- Stop dextrose infusion.
- Administer long-acting insulin dose.
- Continue IV insulin for 1–2 hours after initiating SQ insulin.
- ABCDE survey
- Establish IV access with two large-bore peripheral IV lines.
- Confirm diagnosis with blood gas, BMP, serum osmolality, serum ketones, and urine ketones.
- Identify and treat life-threatening causes (e.g., MI, sepsis).
- Assess severity of DKA.
- Begin fluid resuscitation with 0.9% NaCl.
- Replete potassium and maintain K+ levels at 4–5 mEq/L.
- Replete other electrolytes (see electrolyte repletion).
- Start continuous insulin IV infusion with hourly POC glucose checks once serum potassium is confirmed > 3.3 mEq/L.
- Consider bicarbonate if pH < 6.9 despite adequate fluid therapy.
- Adjust fluid resuscitation based on , serum glucose, and clinical response.
- Identify and treat the underlying cause (e.g., medication nonadherence, infection).
- Order monitoring labs (e.g., BMP, serum osmolality, and blood gas every 2–4 hours).
- Consider endocrine consult.
- Hospital admission; consider ICU admission.
- Other , e.g.:
- Other causes of hyperglycemia and hypovolemia (e.g., sepsis, acute pancreatitis)
- Other hypoglycemia , e.g.,
All other 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. must be considered in the differential diagnosis of