Hyperglycemic Crises in Adult Patients With Diabetes

Abbas E. Kitabchi, PHD, MD; Guillermo E. Umpierrez, MD; John M. Miles, MD; Joseph N. Fisher, MD

Disclosures

Diabetes Care. 2009;32(7):1335-1343. 

In This Article

Pathogenesis

The events leading 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 (ß-hydroxybutyrate and acetoacetate)[19], with resulting ketonemia and metabolic acidosis.

Figure 1.

Pathogenesis of DKA and HHS: stress, infection, or insufficient insulin. FFA, free fatty acid.

Increasing evidence 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-α and interleukin-ß, -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 in the 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 well understood 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 facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent lipolysis and subsequent ketogenesis[12].

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