(HHS) are the two most serious acute metabolic complications of diabetes. DKA is responsible for more than 500,000 hospital days per year (1, 2) at an estimated annual direct medical expense and indirect cost of 2.4 billion USD (2, 3). Table 1 outlines the diagnostic criteria for DKA and HHS. The triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration characterizes DKA. HHS is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. These metabolic derangements result from the combination of absolute or relative insulin deficiency and an increase in counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infections. This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review (4) and more recently published peer-reviewed articles since 2001, which should be consulted for further information.

EPIDEMIOLOGY—Recent epidemiological studies indicate that hospitalizations for DKA in the US are increasing. In the decade from 1996 to 2006, there was a 35% increase in the number of cases, with a total of 136,510 cases with a primary diagnosis of DKA in 2006—a rate of increase perhaps more rapid than the overall increase in the diagnosis of diabetes (1). Most patients with DKA were between the ages of 18 and 44 years (56%) and 45 and 65 years (24%), with only 18% of patients 20 years of age. Two-thirds of DKA patients were considered to have type 1 diabetes and 34% to have type 2 diabetes; 50% were female, and 45% were nonwhite. DKA is the most common cause of death in children and adolescents with type 1 diabetes and accounts for half of all deaths in diabetic patients younger than 24 years of age (5, 6). In adult subjects with DKA, the overall mortality is 1%(1); however, a mortality rate 5% has been reported in the elderly and in patients with concomitant life-threatening illnesses (7, 8). Death in these conditions is rarely due to the metabolic complications of hyperglycemia or ketoacidosis but relates to the underlying precipitating illness (4, 9). Mortality attributed to HHS is considerably higher than that attributed to DKA, with recent mortality rates of 5–20%(10, 11). The prognosis of both conditions is substantially worsened at the extremes of age in the presence of coma, hypotension, and severe comorbidities (1, 4, 8, 12, 13).

PATHOGENESIS—Theeventsleading to hyperglycemia and ketoacidosis are depicted in Fig. 1 (13). In DKA, reduced effective insulin concentrations and increased concentrations of counterregulatory hormones (catecholamines, cortisol, glucagon, and growth hormone) lead to hyperglycemia and ketosis. Hyperglycemia develops as a result of three processes: increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilization by peripheral tissues (12–17). This is magnified by transient insulin resistance due to the hormone imbalance itself as well as the elevated free fatty acid concentrations (4, 18). The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to the release of free fatty acids into the circulation from adipose tissue (lipolysis) and to unrestrained hepatic fatty acid oxidation in the liver to ketone bodies (-hydroxybutyrate and acetoacetate)(19), with resulting ketonemia and metabolic acidosis.