Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious metabolic emergencies that affect patients with type 1 and type 2 diabetes. DKA and HHS are responsible for about 100,000 hospital admissions per year,1 and account for one of every four dollars spent on adult patients with diabetes.2 In one study3 that included 172,796 admissions from 1981 to 1989 in a county teaching hospital, DKA accounted for 28.7 percent of all patients admitted with a primary diagnosis of diabetes. The mortality rate for DKA is less than 5 percent, while the rate for HHS is about 15 percent.4 Important negative prognostic factors in both conditions include patients older than 65 years, hypotension, and coma. Basic common pathophysiologic mechanisms in both conditions consist of a reduction in circulating insulin with increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone).4
Hyperglycemia occurs as a result of accelerated gluconeogenesis, glycogenolysis, and impaired glucose use by muscle and fat tissues. High levels of cortisol also stimulate the breakdown of proteins into amino acids, which then serve as precursors for gluconeogenesis. In patients with DKA, the lack of insulin combined with increased catecholamines results in accelerated lipolysis and production of excess free fatty acids leading to increased beta-oxidation and ketogenesis. However, in patients with HHS, residual beta-cell function, as measured by C-peptide, is adequate to prevent lipolysis, but cannot prevent hyperglycemia.
Although DKA was thought to occur only in patients with type 1 diabetes who require lifelong insulin, recent studies have identified some African Americans with type 2 diabetes who present with DKA, which initially required insulin, but subsequently may be treated with oral agents or diet.5 This condition has been given different names, including atypical diabetes, type 1.5 diabetes, or ketosis-prone diabetes.6
The review articles written by Trachten-barg7 and Stoner8 in this issue of American Family Physician reflect our current understanding of DKA and HHS, based on the recently updated American Diabetes Association guidelines9 that emphasize the importance of adequate fluid and electrolyte replacement, along with physiologic doses of insulin. Because HHS more frequently affects patients with type 2 diabetes and those who were previously undiagnosed, its presentation can be insidious. Older patients and nursing home residents may not be aware of their need for fluid, and consequently develop extensive dehydration and more severe hyperglycemia than patients with DKA.4,10 Therefore, important preventive measures for HHS include frequent monitoring of hydration status, blood glucose levels, and other comorbid conditions.4,9
The most frequent precipitating factor for DKA is infection.4,9 However, recent studies4,11 conducted at inner city hospitals in the United States suggest that the precipitating event often is omission of insulin because patients cannot access or afford medical care. Approximately 50 percent of admissions for DKA may be preventable with improvements in the care of these patients. Furthermore, it also has been shown that quarterly visits for children with type 1 diabetes to endocrine clinics can significantly reduce the number of emergency admissions for DKA.12 A prospective study of 1,243 patients with type 1 diabetes from infancy to 19 years of age showed that elevated A1C levels, underinsurance, and concurrent presence of psychiatric disorders are important predictors of DKA.13
Home blood glucose monitoring equipment with the capability to measure beta-hydroxybutyrate on finger stick blood is now available.14 Home glucose monitoring may reduce admissions for DKA by causing patients to seek care earlier in the course of a hyperglycemic crisis. Because repeated admissions into the emergency department for DKA drain health care dollars, resources should be directed toward improving access to care and educational programs, particularly for socioeconomically disadvantaged groups. Furthermore, resources should be used to educate health care personnel and family members.
The use of low-dose intravenous insulin in the treatment of DKA and HHS is recognized as standard procedure.9 However, most recent studies15,16 on fast-acting insulins (i.e., lispro and aspart) demonstrate that subcutaneous injections of these analogs every one to two hours in patients with mild or moderate DKA on the general hospital wards is as effective as the use of regular intravenous insulin in the intensive care unit, and results in 40 percent cost savings. Furthermore, long-acting peakless insulins such as glargine may provide adequate baseline insulin to reduce the incidence of chronic or acute hyperglycemia. The possibility of preventing DKA in this manner deserves further investigation in randomized clinical trials.
ABBAS E. KITABCHI, PH.D., M.D., F.A.C.P., F.A.C.E., is professor of medicine and molecular sciences and director of the Division of Endocrinology, Diabetes, and Metabolism at the University of Tennessee Health Science Center, Memphis.
Address correspondence to Abbas E. Kitabchi, Ph.D., M.D., F.A.C.P., F.A.C.E., Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee Health Science Center, 956 Court Ave., Room D334, Memphis, TN 38163 (e-mail: email@example.com). Reprints are not available from the author.
1. Graves EJ, Gillum BS. Detailed diagnoses and procedures, National Hospital Discharge Survey, 1995. National Center for Health Statistics. Vital Health Stat 13. 1997;130:133.
2. Javor KA, Kotsanos JG, McDonald RC, Baron AD, Kesterson JG, Tierney WM. Diabetic ketoacidosis charges relative to medical charges of adult patients with type 1 diabetes. Diabetes Care. 1997;20:349–54.
3. Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ. Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. In: Kahn CR, Weir GC, eds. Joslin’s Diabetes mellitus. 13th ed. Philadelphia: Lea & Febiger, 1994:738–70.
4. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001;24:131–54.
5. Balasubramanyam A, Zern JW, Hyman DJ, Pavlik V. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity. Arch Intern Med. 1999;159:2317–22.
6. Kitabchi AE. Ketosis-prone diabetes—a new subgroup of patients with atypical type 1 and type 2 diabetes? [Editorial]. J Clin Endocrinol Metab. 2003;88:5087–9.
7. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005;71:1705–14,1721–2.
8. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2005;71:1723–30.
9. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al. Hyperglycemic crises in diabetes. Diabetes Care. 2004;27(suppl 1):S94–102.
10. Wachtel TJ, Silliman RA, Lamberton P. Predisposing factors for the diabetic hyperosmolar state. Arch Intern Med. 1987;147:499–501.
11. Freire AX, Umpierrez GE, Afessa B, Latif KA, Bridges L, Kitabchi AE. Predictors of intensive care unit and hospital length of stay in diabetic ketoacidosis. J Crit Care. 2002;17:207–11.
12. Vanelli M, Chiari G, Ghizzoni L, Costi G, Giacalone T, Chiarelli F. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care. 1999;22:7–9.
13. Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, et al. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002;287:2511–8.
14. Umpierrez GE, Watts NB, Phillips LS. Clinical utility of beta-hydroxybutyrate determined by reflectance meter in the management of diabetic ketoacidosis. Diabetes Care. 1995;18:137–8.
15. Umpierrez GE, Latif K, Stoever J, Cuervo R, Park L, Freire A, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117:291–6.
16. Umpierrez GE, Cuervo R, Karabell A, Latif K, Freire AX, Kitabchi AE. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004;27:1873–8.
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