Diabetic ketoacidosis


    • An acute metabolic complication of diabetes that is potentially fatal if not properly treated

    • Characterised by absolute insulin deficiency

    • Most common acute hyperglycaemic complication of diabetes

    • Biochemical triad of hyperglycaemia, ketonaemia and acidaemia, with rapid symptom onset.

Risk Factors

    • Strong

      • Inadequate or inappropriate insulin therapy

      • Infection

      • MI

    • Weak

      • Pancreatitis

      • Cerebrovascular accidents

      • Acromegaly

      • Hyperthyroidism

      • Drugs

        • Corticosteroids

        • Sympathomimetics

        • Thiazides

        • Second-generation antipsychotics

        • Cocaine

      • Cushing's syndrome

      • Hispanic or black ancestry

Differential diagnosis

    • Hyperosmolar hyperglycaemic state (HHS)

      • Serum glucose is >13.9 mmol/L (>600 mg/dL). Serum osmolarity is usually >320 mmol/ kg (>320 mOsm/kg).

      • Urine ketones are normal or only mildly positive. Serum ketones are negative.

      • Anion gap is variable but typically <12 mmol/L (<12 mEq/L).

      • Total chloride deficit is 5 to 15 mmol/kg (5 to 15 mEq/kg).

      • ABG:

        • Arterial pH is typically >7.30, whereas in DKA it ranges from 7.00-7.30

        • Arterial bicarbonate is >15 mmol/L (>15 mEq/L)

    • Lactic acidosis

      • The presentation is identical to that of DKA

      • Serum lactate more than 5 mmol/L

    • Starvation ketosis

      • The blood glucose is usually normal.

      • Although the urine can have large amounts of ketones, the blood rarely does.

      • Arterial pH is normal and the anion gap is at most mildly elevated

    • Alcoholic ketoacidosis

  • Salicylate poisoning

    • Ethylene glycol/methanol intoxication

  • Uremic acidosis

      • Elevated urea usually more than 71.4 mmol/L (200 mg/dL)

      • Elevated creatinine usually more than 884 micromol/L (10 mg/dL).


    • In Denmark, the annual incidence of DK is approximately 12.6/100,000 and is higher in men than in women.

      • Twelve per cent of patients, usually those aged over 50 years, were diagnosed with type 2 diabetes

      • Overall mortality was 4%, mainly in patients aged over 70 years.

    • In Sweden, 16% of children with new-onset diabetes presented with DKA

      • Cerebral oedema occurred in 0.68% of cases

    • In Brasil, DKA occurred in 32.8% of patients at diagnosis of type I diabetes

      • Mainly in children aged below 10 years

      • More frequently in non-white than in white people

    • In the US, annual incidence of DKA is estimated to range from 4 to 8 episodes per 1,000 patient admissions with diabetes


    • Reduction in the net effective concentration of circulating insulin

    • Elevation of counterregulatory hormones

      • Glucagon, cortisol, and growth hormone

    • Leads to the extreme manifestations of metabolic derangements that can occur in diabetes

    • The two most common precipitating events are inadequate insulin therapy and infection

    • Underlying medical conditions such as MI or stroke:

      • Provoke the release of counterregulatory hormones

      • Thus also likely to result in DKA in patients with diabetes

    • Drugs that affect carbohydrate metabolism may participate in the development of DKA

      • Corticosteroids, thiazides, sympathomimetic agents, second-generation antipsychotic agents

Clinical features

    • Polyuria

    • Polydipsia

    • Polyphagia

    • Weakness

    • Weight loss

    • Tachycardia

    • Dry mucous membranes

    • Poor skin turgor

    • Hypotension and, in severe cases, shock

    • Kussmaul respiration

    • Acetone breath

    • Altered mental status

    • Hypothermia (uncommon)


    • Reduced insulin concentration or action, along with increased insulin counterregulatory hormones:

      • => hyperglycaemia, volume depletion, and electrolyte imbalance

    • Hormonal alterations =>

      • increased gluconeogenesis

      • hepatic and renal glucose production

      • impaired glucose utilisation in peripheral tissues

      • => hyperglycaemia and hyperosmolarity

    • Insulin deficiency =>

      • release of free fatty acids from adipose tissue (lipolysis)

      • hepatic fatty acid oxidation

      • formation of ketone bodies (beta-hydroxybutyrate and acetoacetate)

        • => ketonaemia and acidosis

    • Elevation of pro-inflammatory cytokines, markers of oxidative stress, lipid peroxidation, and cardiovascular risk factors

      • e.g. C-reactive protein (CRP)

      • Return to normal with insulin and hydration therapies within 24 hours of hyperglycaemic crises

      • May be the result of adaptive responses to acute stress, and not hyperglycaemia per se


    • Elevated plasma glucose

    • ABG

      • pH varies from 7.00 to 7.30

      • Arterial bicarbonate

        • Less than 10 mmol/L (10 mEq/L) in severe diabetic ketoacidosis (DKA)

        • May be more than 15 mmol/L (15 mEq/L) in mild DKA

    • Urinalysis => glucose and ketones

    • Serum sodium is usually low

      • Osmotic reflux of water from the intracellular to extra cellular space in the presence of hyperglycaemia

    • Symptoms of volume depletion

      • Raised serum urea, creatinine

    • Potassium

      • Serum potassium is usually elevated due to extracellular shift of potassium

        • Insulin insufficiency, hypertonicity and acidaemia

      • Total body potassium concentration is low due to increased diuresis

    • Elevated anion gap (more than 10 to 12 mmol/L [10 to 12 mEq/L])

      • Due to the ketones


a) conservative

b) medical

    • Restoration of volume deficits

    • Resolution of hyperglycaemia and ketosis/acidosis

    • Correction of electrolyte abnormalities

      • potassium level should be more than 3.3 mmol/L [3.3 mEq/L] before initiation of insulin therapy

      • Use of insulin in a patient with hypokalaemia may lead to respiratory paralysis, cardiac arrhythmias and death

    • Treatment of the precipitating events and prevention of complications.

c) surgical


    • Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic complication of diabetes

      • Hyperosmolar hyperglycaemic state (HHS) is less common than DKA

        • Less than 1% of all diabetes-related admissions

    • Mortality in patients with DKA is 5% in experienced centres

      • Mortality of patients with HHS is 11%

    • Death in these conditions is rarely caused by the metabolic complications of hyperglycaemia or ketoacidosis

      • Rather relates to the underlying illness

    • The prognosis for both conditions is substantially worsened at the extremes of age

    • Prognosis is worse in the presence of coma and hypotension