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
Ethylene glycol/methanol intoxication
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