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Diabetic ketoacidosis

Definition
  • 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).
Epidemiology
  • 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
Aetiology
  • 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)
Pathophysiology


  • 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

Investigations
  • 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
Management

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

Prognosis
  • 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
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