Diabetes Cetoacidosis

Endocrinol Metab Clin N Am
35 (2006) 725–751

Hyperglycemic Crises in Diabetes
Mellitus: Diabetic Ketoacidosis and
Hyperglycemic Hyperosmolar State
Abbas E. Kitabchi, PhD, MD*,
Ebenezer A. Nyenwe, MD
Division of Endocrinology, Diabetes and Metabolism,
University of Tennessee Health Science Center, 956 Court Avenue,
Suite D334, Memphis, TN 38163, USA

Diabetic ketoacidosis (DKA) andhyperglycemic hyperosmolar state
(HHS) potentially are fatal acute metabolic complications of diabetes [1–6].
DKA accounts for 8% to 29% of all hospital admissions with a primary diagnosis of diabetes. The annual incidence of DKA from population-based
studies is estimated to range from 4 to 8 episodes per 1000 patient admissions
with diabetes [7]. The incidence of DKA continues to increase, withDKA accounting for approximately 115,000 hospitalizations in the United States in
2003 (Fig. 1A) [8]. The rate of hospital admissions for HHS is lower than
for DKA and is less than 1% of all diabetic-related admissions [6,7]. DKA
also is economically burdensome, with an average cost of $13,000 per patient
per hospitalization [9]. Thus, the annual expenditure for the care of patients
who haveDKA may exceed $1 billion. The mortality rate for DKA has been
falling over the years. Age-adjusted mortality rates in the United States dropped by 22% between 1980 and 2001 (from 32 to 20 per 100,000 diabetic population, respectively) (Fig. 1B) [10]. Contrary to the trend in DKA mortality,
the mortality rate of HHS has remained alarmingly high and may exceed
40%, compared with less than 5% inpatients who have DKA [11,12].
DKA consists of the biochemical triad of hyperglycemia, ketonemia, and
metabolic acidosis (Fig. 2) [13]. The terms, hyperglycemic hyperosmolar
nonketotic coma and hyperglycemic hyperosmolar nonketotic state, have
The works of Dr. Kitabchi cited in this article were supported in part by grant number
RR 00211 from the National Institutes of Health, Division ofResearch Resources, Bethesda,
Maryland.
* Corresponding author.
E-mail address: akitabchi@utmem.edu (A.E. Kitabchi).
0889-8529/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.ecl.2006.09.006
endo.theclinics.com

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KITABCHI & NYENWE

Fig. 1. (A) Incidence of DKA. (Centers for Disease Control and Prevention. Diabetes surveillance system. Atlanta: USDepartment of Health and Human Services; 2003. Available at:
www.cdc.gov/diabetes/statistics/index.htm. Accessed June 10, 2006.) (B) Mortality rate of
DKA. (Adapted from Centers for Disease Control and Prevention. Diabetes Surveillance
System. Atlanta GA: US Department of Health and Human Services; 2003. Available at;
www.cdc.gov/diabetes/statistics/mortalitydka. Accessed June 23, 2006.)

beenreplaced with HHS [11,14] to reflect that (1) alterations of sensoria often may be present without coma and (2) HHS may consist of moderate to
variable degrees of clinical ketosis. Although DKA and HHS often are discussed as separate entities, they represent points along a spectrum of

HYPERGLYCEMIC CRISES IN DIABETES MELLITUS

Other Hyperglycemic
States
Uncontrolled DM
HHS
Stresshyperglycemia

Hyperglycemia

Acidosis
DKA

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Other Metabolic Acidotic
States
Lactic acidosis
Hyperchloremic acidosis
Salicylism
Uremic acidosis

Ketosis

Other Ketotic States.
Ketotic hypoglycemia
Alcoholic ketosis
Starvation ketosis
Isopropyl alcohol
Hyperemesis

Fig. 2. Differential diagnosis of DKA. (Adapted from Kitabchi AE, Fisher JN. Diabetes mellitus. In: Glew RA, PetersSP, editors. Clinical studies in medical biochemistry. New York:
Oxford University Press; 1987. p. 105.)

emergencies caused by poorly controlled diabetes. DKA and HHS are characterized by absolute or relative insulinopenia. Clinically, they differ only by
the severity of dehydration, ketosis, and metabolic acidosis [2,4,6]. DKA occurs most often in patients who have type 1 diabetes mellitus...