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