Diabetic ketoacidosis is an acute, major, life-threatening complication of diabetes. It occurs mainly in patients with type 1 diabetes but is not uncommon in those with type 2 diabetes.
It is clinically defined as an acute status of severe uncontrolled diabetes that requires emergency treatment with insulin and intravenous fluids. Biochemically, diabetic ketoacidosis is defined by an increase in serum ketone levels above 5 mEq/l, blood glucose above 250 mg/dl, blood pH below 7.2, and a bicarbonate level of 18 mEq/l.
Although diabetic ketoacidosis was a common problem in diabetic patients who were treated with continuous subcutaneous insulin infusion through infusion pumps, the incidence of complication has become less common since the introduction of new pumps equipped with sensitive electronic alarm systems that alert the patient when his catheter stuck.
Diabetic ketoacidosis also occurs in pregnant women with pre-existing or diagnosed diabetes during pregnancy. Pregnancy is a medical emergency because the mother and fetus are at increased risk of mortality and morbidity.
When ketoacidosis is treated correctly it rarely causes residual effects. Mortality varies between 1-10%. Cerebral edema remains the most common cause of mortality, especially in young children and adolescents. It often results in rapid fluid cell exchange. Other causes of mortality include severe hypokalemia, adult respiratory distress syndrome, and comorbidities: pneumonia, myocardial infarction.
The early symptoms of diabetic ketoacidosis are polyuria and polydipsia. Then there is nausea, abdominal pain, weakness, altered consciousness, confusion. Diabetic ketoacidosis is a status of absolute or relative insulin deficiency aggravated by hyperglycemia, dehydration and acidosis.
Emergency treatment for diabetic ketoacidosis involves the administration of isotonic saline, especially in the presence of hypotension, tachycardia, or other signs of volume depletion. The signs of infection, stroke, sepsis, myocardial infarction will be followed. Potassium, phosphate, bicarbonate will be replaced – all deficient. Insulin will be given. Diabetic ketoacidosis accounts for 14% of diabetes fatalities. The current mortality rate is 2%.
Pathogenesis of diabetic ketoacidosis
Diabetic ketoacidosis is an altered metabolic status characterized by hyperglycemia, acidosis, and ketonuria. It usually occurs as a consequence of absolute or relative insulin deficiency accompanied by an increase in counter-regulatory hormones: glucagon, catecholamines, cortisol, growth hormone. Determines the activation of hepatic gluconeogenesis, glycogenolysis, and lipolysis.
Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency and excess counter-regulatory hormones cause severe hyperglycemia, while lipolysis increases free fatty acids.
Hepatic fatty acid metabolism is an alternative source of energy-ketogenesis with an accumulation of ketones and keto acids. Ketones include acetone, beta-hydroxybutyrate, and acetoacetate.
The progressive increase of these acids in the blood leads to ketonuria. When the accumulation of ketones exceeds the body’s ability to extract them, they are excreted in the urine. If the situation is not treated, the accumulation of ketones leads to metabolic acidosis with a decrease in pH and bicarbonate. Respiratory compensation of acidosis causes Kussmaul’s breathing. Ketones, particularly hydroxybutyrate, cause nausea and vomiting that aggravate electrolyte loss. They also produce the characteristic smell of acetone.
Hyperglycemia causes glycosuria. Water loss through urine is increased by glycosuria-induced osmotic diuresis. This causes dehydration, thirst, tissue hypoperfusion, and lactic acidosis. Hyperglycemia, osmotic diuresis, serum hyperosmolarity, and metabolic acidosis cause severe electrolyte abnormalities. The most characteristic is hypokalemia.
Causes and risk factors for diabetic ketoacidosis
Patients with type 1 diabetes:
- acute insulin deficiency, poor patient compliance with insulin therapy
- bacterial infections, repeated vomiting
- Klebsiella pneumonia is the leading cause of infections that precipitate ketoacidosis
- medical, emotional, or surgical stress
- blockage of the insulin infusion catheter.
Patients with type 2 diabetes:
- intercurrent diseases: myocardial infarction, pneumonia, prostatitis, urinary tract infections
- medication: corticosteroids, pentamidine, clozapine
- stroke, complicated pregnancy, trauma, cocaine, acromegaly.
Signs and symptoms
Among people with type 1 diabetes, diabetic ketoacidosis is more common in children and adolescents than in adults. Early symptoms are polyuria, thirst. Nausea and vomiting usually occur as well being associated with diffuse abdominal pain. Generalized weakness and fatigue appear. An altered state of consciousness in the form of slight disorientation or confusion is a possible symptom. Although coma is uncommon, it can occur when the condition is neglected or acidosis and dehydration are severe.
Symptoms of an associated intercurrent infection may include fever, dysuria, cough, malaise, arthralgia. Acute angina or palpitations may occur in association with myocardial infarction. Painless infarction is common in diabetics and should be suspected in the elderly. Patients may experience a lack of insulin injections.
The classic signs of hyperglycemia:
- thirst, polyuria, polydipsia, nocturia.
- generalized weakness, malaise, lethargy
- nausea, vomiting, decreased perspiration, anorexia, and has increased appetite
- confusion, dry skin, dry mucous membranes, decreased reflexes
- tachycardia, hypotension, hypothermia, fever in case of infections
- abdominal tenderness.
Physical examination of diabetic ketoacidosis
- signs of dehydration: weak and fast pulse, dry tongue and dry skin, hypotension, increased time of capillary refilling, the characteristic smell of respiration – acetone.
- signs of acidosis: rapid shallow breathing or thirst for air, abdominal tenderness, alterations of consciousness.
Cerebral edema is a severe complication that can develop during diabetic ketoacidosis. Deterioration of consciousness despite improved metabolic status indicates recurrence of cerebral edema.
Magnetic resonance imaging is used to confirm the diagnosis. If the cerebral edema appears at the initiation of the therapy it worsens during it. Clinical cerebral edema is rare and has a high mortality rate. Mannitol and dexamethasone are used.
Cardiac arrhythmias may occur secondary to severe hypokalemia and / or acidosis. Correcting the cause is enough to treat them.
Pulmonary edema can occur for the same reasons as cerebral edema. Although rare, it can be caused by correction of fluid depletion. Diuretics and oxygen therapy are sufficient to control pulmonary edema.
Nonspecific myocardial lesions associated with increased levels of specific myocardial markers: troponins and CK-MB. The initial EKG changes are similar to myocardial infarction.
Acidosis and fatty acids can cause membrane instability of myocytes. Microvascular changes consist of diabetic retinopathy.
Diabetic ketoacidosis is diagnosed by the following:
- Blood tests
- The urine dipstick test is positive for glucose and ketones
- the predominant ketone is hydroxybutyrate
- urine culture helps determine a possible infection
- blood glucose is over 250 mg/dl
- serum ketones are present and are highlighted by bands
- arterial gases show typical manifestations of metabolic acidosis, bicarbonate, and low pH
- serum sodium levels are low, serum chlorine and phosphorus levels are low
- the anion hole is large, the plasma osmolality is increased over 290 mOsm / l
- urinary osmolarity is increased
- even in the absence of infection, the blood count shows an increased number of white blood cells
- Increased INR, blood culture helps identify an infection.
- Imaging tests – A simple chest x-ray shows signs of pneumonia. Magnetic resonance imaging is useful in detecting cerebral edema. The electrocardiogram shows signs of an acute infarction that is painless in diabetics, especially in those with autonomic polyneuropathy. T-wave changes are the first sign of hypokalemia.
Emergency treatment for diabetic ketoacidosis involves the administration of isotonic saline, especially in the presence of hypotension, tachycardia, or other signs of volume depletion.
The signs of infection, stroke, sepsis, myocardial infarction will be followed. Potassium, phosphate, bicarbonate will be replaced – all deficient. Insulin will be given.
Diabetic ketoacidosis accounts for 14% of diabetes fatalities. The current mortality is 2%.
Treatment should be started within 24-48 hours of onset. This includes correcting fluid imbalances, insulin therapy, correcting electrolytes, especially hypokalemia, correcting acid-base imbalance and intercurrent infection if present.