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])
Managementa) conservativeb) 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) surgicalPrognosis- 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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