- Clinical science
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.
- Lack of or insufficient insulin replacement therapy
- Increased insulin demand
Primarily affects patients with type 1 diabetes
- 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.
Metabolic acidosis with increased anion gap
- Insulin deficiency also increased 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.
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.
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.
Signs and symptoms of both DKA and HHS
- Recent weight loss
- Nausea and vomiting
- Signs of volume depletion (i.e., dry mucous membranes, decreased skin turgor), hypotension, circulatory collapse
- Neurological abnormalities
- Signs and symptoms specific to DKA
|Clinical findings of DKA versus HHS|
|Diabetes||Type 1||Type 2|
|History of severe stress, illness, hospitalization||+||+|
|Altered mental status||Possible||Possible|
|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
↑ Serum glucose
- < 600 mg/dL → DKA
- > 600 mg/dL → HHS
- Urine ketones
- Serum electrolytes, including bicarbonate (with anion gap calculation)
- Arterial blood gas if serum bicarbonate is reduced
- Plasma osmolality (if HHS is suspected)
- ↑ Serum glucose
- 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)|
|Arterial pH|| |
7.0 to < 7.2
10 to < 15 mEq/L
|< 10 mEq/L|
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|
|Onset||Hours to days||Minutes|
|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.
- 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.