Epidemiology

Diabetic ketoacidosis (DKA) classically occurs in patients with type 1 diabetes mellitus but may also occasionally develop in patients with type 2 diabetes. Type 1 diabetes refers to insulin deficiency due to autoimmune destruction of the insulin-producing beta-cells of the pancreas. In the past, type 1 diabetes was called “juvenile” or “insulin-dependent” diabetes. However, these terms are no longer used because this disease can present at any age (patients in their 80s can develop type 1 diabetes), and patients with type 2 diabetes can also be “insulin-dependent.” Type 2 diabetes accounts for more than 90% of all cases of diabetes, and it is characterized by relative insulin deficiency and insulin resistance. Type 2 diabetes has been called “non-insulin dependent” or “adult-onset” diabetes, but these terms are also outdated since these patients usually become insulin-dependent as their disease progresses and are presenting at younger ages (even in childhood) because of the increasing obesity epidemic.

The incidence of DKA is 46 to 80 per 10,000 person-years among patients with diabetes, and the estimated mortality rate of DKA is 4% to 10%. Only 20% of DKA episodes occur in patients with new-onset diabetes. Furthermore, 20% of patients with DKA have multiple annual episodes. Therefore, patient education and compliance are crucial for reducing the incidence of DKA.

Pathogenesis

The hallmark of DKA is severe insulin deficiency and inappropriate glucagon excess that leads to hyperglycemia and hyperketonemia. Insulin deficiency stimulates hepatic glucose production and causes the release of large amounts of free fatty acids from adipose tissue. The free fatty acids are converted to ketone bodies (acetoacetate and beta-hydroxybutyrate) in the liver, leading to acidosis. Glucagon secretion is inappropriately increased in DKA and directly stimulates ketogenesis as well as gluconeogenesis (glucose production) in the presence of insulin deficiency. The excess glucose production cannot be utilized by muscle or fat (insulin is required for glucose uptake by these tissues), leading to hyperglycemia.

Therefore, the features of DKA are:

Precipitants

The major precipitants of DKA (Box 5-1) commonly include cessation of insulin (endogenous or exogenous), infection, and stress (such as myocardial infarction or stroke, but perhaps also emotional stress in certain patients) although no precipitating event is identified in up to one-fourth of patients. Coexisting medical illness is the most common factor and accounts for at least one half of the causes of DKA.

Symptoms

Patients commonly present with polyuria (excessive urination), polydipsia (excessive thirst), nausea, vomiting, and abdominal pain. Dehydration is typical in DKA because the high urinary glucose concentrations cause diuresis, leading to the usual complaints of polyuria and polydipsia. Weight loss is often a prominent feature in patients with undiagnosed diabetes because their symptoms have typically progressed over several weeks. Fever is not a feature of DKA itself and suggests underlying infection.