INTRODUCTION AND EPIDEMIOLOGY
Diabetes is subclassified into type 1 and type 2. Type 1 diabetes, previously referred to as insulin-dependent diabetes mellitus or juvenile-onset diabetes because of its earlier onset, is characterized by an abrupt and frequently complete decline in insulin production. Type 2 diabetes, formerly referred to as non–insulin-dependent diabetes mellitus or adult-onset diabetes, is marked by increasing insulin resistance and most commonly occurs in the overweight adult or adolescent; there is a strong genetic tendency toward the disease. Gestational diabetes can affect pregnant teens as well as the infants of diabetic mothers. There has been an increase in the prevalence of type 1 diabetes of 21% between 2001 and 2009 and an increase of 31% in type 2 diabetes in the same time period.1 While the cause of the increase in type 1 diabetes is unknown, some experts suggest that the increasing prevalence of type 2 diabetes may be a result of minority population growth, obesity, exposure to diabetes in utero, and perhaps endocrine-disrupting chemicals.1 Diabetes is the most common pediatric endocrine disorder, with an estimated prevalence of 1 in 400. As many as 34% of children with new-onset type 1 diabetes present in diabetic ketoacidosis (DKA).2 In children with known diabetes, DKA is much less common and tends to be clustered in a small subset of patients, with 5% of children with diabetes accounting for nearly 60% of DKA episodes.3 DKA is the leading cause of mortality in patients with diabetes <24 years of age, and cerebral edema is the leading cause of mortality in DKA.4
PATHOPHYSIOLOGY AND CLINICAL FEATURES
The fundamental cause of DKA is an absolute or relative insulin deficiency that results in the inability of cells to take up and use glucose. Levels of counterregulatory hormones (catecholamines, cortisol, growth hormone, and glucagon) are elevated, which drives many of the physiologic disturbances observed in DKA. These hormones increase glucose production by promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis, and further decrease glucose utilization by antagonizing insulin.
As the serum glucose level exceeds the renal absorption threshold, an obligatory osmotic diuresis ensues, which results in the classic symptoms of polyuria and polydipsia. If not recognized early, this can lead to profound dehydration and electrolyte disturbances. Acidosis stems from the complex metabolic derangements induced by insulin deficiency and unopposed glucagon. The cellular milieu of the body is essentially in a state of functional starvation, unable to use the excess serum glucose. Decreased lipid uptake by adipose tissue and increased lipolysis result in an overabundance of circulating free fatty acids, which are converted by the liver into the ketoacids acetoacetate and β-hydroxybutyrate.
Despite this profound shift in substrate production, ketoacid utilization and renal elimination are both impaired, which results in a wide anion gap metabolic acidosis. In certain patients, the acid-base status may be more complex. Persistent vomiting and severe volume depletion may result in a superimposed metabolic alkalosis that may mask the severity of the acidosis by ...