Diabetic ketoacidosis

Definition

Diabetic ketoacidosis (DKA) is an acute, life-threatening metabolic decompensation caused by insulin deficiency. It is characterized by the triad of hyperglycemia, hyperketonemia and metabolic acidosis with an increased anion gap. Osmotic diuresis leads to substantial losses of water and electrolytes.

In euglycemic DKA, ketoacidosis occurs without markedly elevated glucose, e.g. in pregnancy, in alcohol misuse or liver cirrhosis, and drug-induced.

Occurrence & epidemiology

DKA occurs predominantly in type 1 diabetes and is the first manifestation in about one third of patients. In type 2 diabetes it is less common and develops mainly under unusual physiological stress; a special form is ketosis-prone type 2 diabetes (Flatbush diabetes), which occurs more often in people of African ancestry with obesity.

Aetiopathogenesis

Precipitating factors

Insulin deficiency may be absolute or relative, when requirements rise under physiological stress:

• acute infections (e.g. pneumonia, urinary tract infection, COVID-19)
• myocardial infarction, stroke, pancreatitis, trauma
• pregnancy
• new-onset type 1 diabetes
• drug-induced, e.g. glucocorticoid-induced

Pathophysiology

• Hormonal imbalance: insulin deficiency with a simultaneous rise in counter-regulatory hormones (glucagon, catecholamines, cortisol).
• Lipolysis and ketogenesis: unrestrained lipolysis releases glycerol and free fatty acids. Glucagon promotes their conversion to ketone bodies (acetoacetate, beta-hydroxybutyrate) in hepatic mitochondria; these strong organic acids cause the acidosis. Acetone is partly exhaled.
• Gluconeogenesis: glycerol and alanine from muscle breakdown serve as substrate for the liver; hyperglycemia worsens.
• Osmotic diuresis: glucose and ketone bodies in the urine carry water, sodium and potassium with them.
• Potassium: despite a substantial total-body deficit, serum potassium is often normal or raised initially because acidosis shifts potassium out of the cells.

Clinical features

Leading symptoms are:

• polyuria, polydipsia, weakness
• nausea, vomiting, and abdominal pain, particularly in children (pseudoperitonitis)
• deep, rapid breathing (Kussmaul respiration) as respiratory compensation, fruity acetone odour of the breath
• dehydration, tachycardia, hypotension
• lethargy and somnolence progressing to coma

Fever is not a feature of DKA itself and points to a precipitating infection. Cerebral edema occurs in less than 1 %, mainly in children; warning signs are headache and a fluctuating level of consciousness, and sometimes respiratory arrest is the first sign.

Diagnosis

Diagnostic criteria

• arterial or venous pH < 7.30
• anion gap > 10–12 mmol/l
• serum bicarbonate < 15–18 mmol/l
• ketone bodies in serum or urine
• glucose > 200–250 mg/dl (11.1–13.8 mmol/l); some guidelines accept known diabetes instead of a cut-off in order to capture euglycemic cases

DKA and HHS compared

• DKA: glucose > 200–250 mg/dl (11.1–13.8 mmol/l) or known diabetes; pH < 7.30, bicarbonate < 15–18 mmol/l, increased anion gap; ketone bodies in serum or urine.
• HHS: glucose ≥ 600 mg/dl (≥ 33.3 mmol/l); serum osmolality > 300 mosmol/kg; no relevant ketosis (urine ketones < 2+ or beta-hydroxybutyrate < 3.0 mmol/l); pH ≥ 7.3 and bicarbonate ≥ 15 mmol/l.
• Consciousness: in HHS, impaired consciousness is the leading symptom; in DKA, lethargy and somnolence occur with severe decompensation.
• Mixed forms: overlap between DKA and HHS has been described in more than one third of hyperglycemic crises.

Further findings

• Ketone bodies: urine test strips and some serum assays detect only acetoacetate, not the usually predominant beta-hydroxybutyrate, and therefore underestimate ketosis; beta-hydroxybutyrate can be measured directly in blood.
• Electrolytes and kidney: sodium (often dilutionally low because of hyperglycemia), potassium, urea, creatinine, osmolality.
• Other laboratory values: amylase and lipase are often raised even without pancreatitis.
• ECG: in adults to look for myocardial infarction and to assess the effects of potassium.
• Search for the trigger: targeted tests according to the clinical picture, e.g. cultures and imaging.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Acute Complications of Diabetes Mellitus
2. Umpierrez et al.: Hyperglycemic Crises in Adults With Diabetes – A Consensus Report (Diabetes Care 2024)

Cross-references