Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus. DKA occurs predominantly in patients with type 1 (insulin-dependent) diabetes mellitus, but 10% to 30% of cases occur in newly diagnosed type 2 (non–insulin-dependent) diabetes mellitus, especially in African Americans and Hispanics.1,2 Between 1993 and 2003, the yearly rate of U.S. ED visits for DKA was 64 per 10,000 with a trend toward an increased rate of visits among the African American population compared with the Caucasian population.3 Europe has a comparable incidence. A better understanding of the pathophysiology of DKA and an aggressive, uniform approach to its diagnosis and management have reduced mortality to <5% of reported episodes in experienced centers.4 However, mortality is higher in the elderly due to underlying renal disease or coexisting infection and in the presence of coma or hypotension.
Figure 220-1 illustrates the complex relationships between insulin and counterregulatory hormones. DKA is a response to cellular starvation brought on by relative insulin deficiency and counterregulatory or catabolic hormone excess (Figure 220-1). Insulin is the only anabolic hormone produced by the endocrine pancreas and is responsible for the metabolism and storage of carbohydrates, fat, and protein. Counterregulatory hormones include glucagon, catecholamines, cortisol, and growth hormone. Complete or relative absence of insulin and the excess counterregulatory hormones result in hyperglycemia (due to excess production and underutilization of glucose), osmotic diuresis, prerenal azotemia, worsening hyperglycemia, ketone formation, and a wide-anion-gap metabolic acidosis.4
Insulin deficiency. Pathogenesis of diabetic ketoacidosis secondary to relative insulin deficiency and counterregulatory hormone excess. GFR = glomerular filtration rate.
Ingested glucose is the primary stimulant of insulin release from the β cells of the pancreas. Insulin's main action occurs at the three principal tissues of energy storage and metabolism—the liver, adipose tissue, and skeletal muscle. Insulin acts on the liver to facilitate the uptake of glucose and its conversion to glycogen while inhibiting glycogen breakdown (glycogenolysis) and suppressing gluconeogenesis. The net effect of these actions is to promote the storage of glucose in the form of glycogen. Insulin increases lipogenesis in the liver and adipose cells by producing triglycerides from free fatty acids and glycerol while inhibiting the breakdown of triglycerides. Insulin stimulates the uptake of amino acids into muscle cells with subsequent incorporation into muscle protein while preventing the release of amino acids from muscle and hepatic protein sources.
Deficiency in insulin secretion due to loss of islet cell mass is the predominant defect in type 1 diabetes mellitus. In the initial stages of diabetes mellitus, the secretory failure of β cells impairs fuel storage and may be evident only during a glucose tolerance test. As levels of insulin decrease, fuel stores are mobilized during fasting, resulting in hyperglycemia. When pancreatic β-cell reserve is present, hyperglycemia may trigger an increase in insulin and a return to normal ...