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Chapter 36
Diabetic emergencies
Diabetic ketoacidosis
The triad of diabetic ketoacidosis (DKA) consists of hyperglycaemia, high anion gap metabolic acidosis and ketonaemia. DKA is characteristically associated with type 1 diabetes. However, it has become increasingly common in patients with type 2 diabetes.
Aetiology and pathogenesis
The precipitating factors for DKA are summarized in Box 36.1. DKA may be the first presentation of type 1 diabetes. DKA may occasionally be the first presentation of type 2 diabetes, especially in Afro-Caribbean individuals (‘ketosis-prone type 2 diabetes’).
In patients with known diabetes, inadequate insulin treatment or non-compliance is a common precipitating factor for DKA. DKA may also be precipitated by stresses that increase the secretion of the counterregulatory hormones glucagon, catecholamines, cortisol and growth hormone. Infection, such as pneumonia, gastroenteritis and urinary tract infection, can be found in about 30–40% of patients with DKA.
Insulin deficiency causes impaired glucose utilization, as well as increased gluconeogenesis and glycogenolysis, resulting in hyperglycaemia. The elevated plasma glucose increases the filtered load of glucose in the renal tubules. As the maximal renal tubular reabsorptive capacity is exceeded, glucose is excreted in the urine (glycosuria). The osmotic force exerted by unreabsorbed glucose holds water in the tubules, thereby preventing its reabsorption and increasing urine output (osmotic diuresis). This leads to dehydration and loss of electrolytes.
Insulin deficiency and increased catecholamines and growth hormone increase lipolysis, thereby increasing free fatty acid delivery to the liver. Normally, free fatty acids are converted to triglycerides in the liver. However, in DKA, hyperglucagonaemia alters hepatic metabolism to favour ketogenesis. Glucagon excess decreases the production of malonyl coenzyme A, thereby increasing the activity of the mitochondrial enzyme carnitine palmitoyltransferase I. Carnitine palmitoyltransferase I mediates the transport of free fatty acyl coenzyme A into the mitochondria, where conversion to ketones occurs.
Three ketone bodies are produced in DKA: two ketoacids (beta-hydroxybutyric acid and acetoacetic acid) and one neutral ketone (acetone). Acetoacetic acid is the initial ketone formed. It may then be reduced to beta-hydroxybutyric acid, or non-enzymatically decarboxylated to acetone. Ketones provide an alternate source of energy when glucose utilization is impaired.
Hyperglycaemic crises are proinflammatory states that lead to the generation of reactive oxygen species, which are indicators of oxidative stress.
Clinical presentations
Patients with DKA may present with:
- polyuria and polydipsia resulting in dehydration
- abdominal pain and vomiting (which exacerbates the dehydration). Abdominal pain requires further evaluation if it does not resolve with treatment of the acidosis
- fatigue, weakness and weight loss
- confusion; coma (10% of patients).
Clinical examination includes assessment of cardiorespiratory status, volume status and mental status to look for:
- evidence of dehydration: tachycardia, postural hypotension, reduced tissue turgor and confusion
- Kussmaul’s respiration (deep sighing respiration secondary to acidosis) and ketotic breath.
A medical history and clinical examination may identify a precipitating event such as infection (e.g. pneumonia, urinary tract infection) or discontinuation of or inadequate insulin therapy in known diabetics.
Investigations
The investigations in patients presenting with DKA are summarized in Box 36.2. The diagnosis of DKA requires:
- plasma glucose >11 mmol/L (and usually <44 mmol/L)
- positive urinary ketones, or plasma ketones >3 mmol/L
- acidosis (pH ≤ 7.30, bicarbonate <15 mmol/L). The acidosis in DKA is a metabolic acidosis (associated with low bicarbonate levels and a reduction of partial pressure of carbon dioxide [PCO2] due to compensatory hyperventilation) with a high anion gap (>12 mmol/L).
The plasma anion gap is calculated from the difference between the primary measured cations and the primary measured anions, i.e. serum [Na+ + +]-serum [Cl− + HCO3 −].
In normal subjects, the anion gap is primarily determined by the negative charges on the plasma proteins, particularly albumin. The anion gap is elevated in those forms of metabolic acidosis in which there is buffering of the excess acid by bicarbonate (resulting in a reduction of bicarbonate) and replacement of the bicarbonate by an unmeasured anion (e.g. ketoacid anions in DKA).
Blood glucose levels as low as 10 mmol/L and severe acidaemia may be seen in patients who have recently taken insulin, as this alone is insufficient to correct the acidosis in the presence of dehydration.
Urine ketone detection systems generally detect acetoacetic acid and acetone, but not beta-hydroxybutyric acid. Sulfhydryl drugs, such as captopril, penicillamine and mesna, interact with the nitroprusside reagent and can cause a false-positive ketone test. In patients treated with these drugs, direct measurement of beta-hydroxybutyric acid is recommended. Capillary ketone meters measure the level of beta-hydroxybutyric acid, which is the principal ketone produced in DKA.
A septic screen should be performed to look for an underlying infection. An electrocardiogram (ECG) should be done to exclude acute coronary syndrome as a precipitating factor.
The white cell count may be elevated due to an underlying infection. However, an elevated white cell count (usually less than 25 × 109/L) is also commonly seen in the absence of infection. This may occur as a result of hypercortisolaemia and increased catecholamine secretion.
Serum amylase and lipase levels are elevated in 15–25% of patients with DKA and, in most cases, do not reflect acute pancreatitis. However, acute pancreatitis may occur in about 10% of patients with DKA (often in association with hypertriglyceridaemia). The diagnosis of pancreatitis in patients with DKA should be based upon the clinical findings and a computed tomography (CT) scan.
Differential diagnosis
Ketoacidosis may also be caused by alcohol abuse or fasting. Other causes of a high anion gap metabolic acidosis include lactic acidosis (due to tissue hypoperfusion caused by hypovolaemia, cardiac failure or sepsis), renal failure and drugs such as aspirin, methanol and ethylene glycol.
Treatment
Patients should ideally be managed and closely monitored in a high-dependency or intensive therapy unit. Treatment of DKA includes:
- resuscitation (airway, breathing, circulation)
- insulin
- fluids
- potassium.
Broad-spectrum antibiotics are given if infection is suspected.
Patients should remain nil by mouth for at least 6 hours as gastroparesis is common. In patients with impaired conscious level, a nasogastric tube is inserted to prevent vomiting and aspiration.
Two intravenous cannulae should be sited, one in each arm: one for 0.9% saline and one for insulin and later 5% dextrose. A urinary catheter is inserted in patients with oliguria or elevated serum creatinine. A central line may be inserted in those with a history of cardiac disease or autonomic neuropathy and in those who are elderly.
All patients should have thromboprophylaxis with low molecular weight heparin.
Insulin replacement
The only indication for delaying insulin is a serum potassium less than 3.3 mmol/L, as insulin will worsen the hypokalaemia by driving potassium into the cells. Patients with an initial serum potassium of less than 3.3 mmol/L should receive fluid and potassium replacement prior to insulin.
Fifty units of soluble insulin are added to 50 mL 0.9% saline. Insulin infusion is started at a fixed rate of 0.1 U/kg per hour (approximately 6–7 U per hour). The response to insulin infusion is reviewed after 1 hour. If blood glucose level is not dropping by 5 mmol per hour and capillary ketones by 1 mmol per hour, the infusion rate is increased by 1 per hour.
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