Diagnostic criteria for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)




Mild Moderate Severe
Plasma Glucose >250 >250 >250 >600
Arterial PH 7.25 - 7.30 7.00 - 7.24 <7.00 >7.30
Serum HCO3 15-18 10 to <15 <10 >18
Urine Ketones* (+) (+) (+) (-) or small
Serum Ketones* (+) (+) (+) (-) or small
Effective Serum Osm. Variable Variable Variable >320
Anion gap Δ >10 >12 >12 Variable (<12)
Alteration in sensoria or mental obtundation Alert Alert


Hyperosmolar hyperglycemic syndrome (HHS), also known as non-ketotic hyperglycemic hyperosmolar syndrome (NKHS), is characterized by profound hyperglycemia (glucose >600 mg/dL), hyperosmolality (effective serum osmolality >320 mOsm/kg), and volume depletion in the absence of significant ketoacidosis (pH >7.3 and HCO3 >15 mEq/L), and is a serious complication of diabetes. HHS may be the first presentation of type 2 diabetes. Although both HHS and diabetic ketoacidosis (DKA) are often discussed as distinct entities, they represent 2 points on the spectrum of metabolic derangements in diabetes, both HSS and DKA being characterized by relative or absolute insulin deficiency combined with increased counter-regulatory hormones. Approximately one third of patients with hyperglycemic crises present with a mixed picture of DKA and HSS.

Resolution Criteria

Criteria for HHS resolution:

  1. Glucose 250 to 300 mg/dL (13.9 to 16.7 mmol/L)

Physical Exam

Key Factors
  • Altered mental status

Other Factors

  • Polyuria, Polydypsia, Polyphagia, Weight loss, Weakness.
  • Dry mucous membranes
  • Poor skin turgor
  • Tachycardia
  • Hypotension
  • Seizures
  • Hypothermia
  • Shock
  • Abdominal pain
  • Focal neurologic signs


1st Tests To Order:
  • Plasma glucose,
  • CBC, CMP (BUN, creatinine, Na, K, Cl ).
  • Serum Ca, Mg, Phos, Lactate level.
  • LFTs
  • Serum osmolality
  • Anion gap calculation
  • ABG
  • UA
Other Tests to Consider:
  • Serum ketones/serum beta-hydroxybutyrate
  • CXR, ECG
  • Myocardial enzymes x 3 q6h
  • Blood, urine, or sputum cultures


When to Stop IV insulin?

The ADA guidelines suggest that the IV Insulin infusion can be tapered, and a multiple-dose subcutaneous (SC) insulin schedule started, in patients who meet the following goals (the last three apply only to DKA):
  • Serum glucose
    • DKA< 200 mg/dL (11.1 mmol/L)
    • HHS - 250 to 300 mg/dL (13.9 to 16.7 mmol/L)
  • Serum anion gap <12 meq/L (or less than the upper limit of normal for the local laboratory)
  • Serum bicarbonate ≥18 meq/L
  • Venous pH >7.30




Insulin-related hypoglycemia:
  • This iatrogenic complication can occur with excessive high-dose insulin therapy.
    It can be prevented by following treatment protocols with frequent monitoring of plasma glucose and use of glucose-containing IV fluids

Treatment-related hypokalemia

  • This iatrogenic complication can occur with excessive high-dose insulin therapy, inadequate potassium replacement, and bicarbonate therapy.
    It can be prevented by following treatment protocols with frequent monitoring of potassium levels and appropriate replacement

Cerebrovascular accident, Myocardial infarction, Pulmonary Embolus, DIC, Mesenteric Vessel Thrombosis.

  • Reported as a complication of hyperosmolar hyperglycemic syndrome (HHS). Predisposing factors include volume depletion with increased viscosity, hyperfibrinogenemia, and elevated levels of plasma plasminogen activator inhibitor (PAI-1).
    Aggressive early hydration is helpful in reducing the incidence of these complications to approximately 2%. There is no evidence for full anticoagulation. Prophylactic treatment is based on clinical evaluation of risk factors for thromboembolic events

Cerebral edema

  • This is rare in adults with HHS. It presents with headache, lethargy, papillary changes, and seizure. Mortality is high.
    Mannitol infusion and mechanical ventilation should be used. Prevention may be achieved by avoidance of overzealous hydration and by stabilizing plasma glucose levels.


  • Usually associated with serum osmolality levels >330 to 340 mOsm/kg and is most often more hypernatremic than hyperglycemic in nature.
    ICU admission, close monitoring, and aggressive fluid and insulin therapy are necessary. Many patients may require airway protection and mechanical ventilation.