Diabetes

Reviews/Commentaries/ADA Statements
C O N S E N S U S S T A T E M E N T

Hyperglycemic Crises in Adult Patients With Diabetes
ABBAS E. KITABCHI, PHD, MD1 GUILLERMO E. UMPIERREZ, MD2 JOHN M. MILES, MD3 JOSEPH N. FISHER, MD1 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 fattyacid 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. Increasingevidence indicates that the hyperglycemia in patients with hyperglycemic crises is associated with a severe inflammatory state characterized by an elevation of proinflammatory cytokines (tumor necrosis factor- and interleukin- , -6, and -8), C-reactive protein, reactive oxygen species, and lipid peroxidation, as well as cardiovascular risk factors, plasminogen activator inhibitor-1 and free fatty acids inthe absence of obvious infection or cardiovascular pathology (20). All of these parameters return to near-normal values with insulin therapy and hydration within 24 h. The procoagulant and inflammatory states may be due to nonspecific phenomena of stress and may partially explain the association of hyperglycemic crises with a hypercoagulable state (21). The pathogenesis of HHS is not as wellunderstood as that of DKA, but a greater degree of dehydration (due to osmotic diuresis) and differences in insulin availability distinguish it from DKA (4,22). Although relative insulin deficiency is clearly present in HHS, endogenous insulin secretion (reflected by C-peptide levels) appears to be greater than in DKA, where it is negligible (Table 2). Insulin levels in HHS are inadequate to facilitateglucose utilization by insulinsensitive tissues but adequate to prevent lipolysis and subsequent ketogenesis (12). PRECIPITATING FACTORS — The most common precipitating factor in the development of DKA and HHS is infection (1,4,10). Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and
1335

Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (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 growthhormone). 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 technicalreview (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 U.S. 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...