Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults

INTRODUCTION

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS, also known as nonketotic hyperglycemia) are two of the most serious acute complications of diabetes. They are part of the spectrum of hyperglycemia and each represents an extreme in the spectrum.

The clinical features and diagnosis of DKA and HHS will be reviewed here. The epidemiology, pathogenesis, and treatment of these disorders are discussed separately. (See "Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic state" and "Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults".)

DEFINITIONS

DKA and HHS differ clinically according to the presence of ketoacidosis and usually the degree of hyperglycemia [1-4]. The definitions proposed by the American Diabetes Association for DKA and HHS are shown in a table, along with criteria for classification of DKA as mild, moderate, or severe, based on the patient's arterial pH, serum bicarbonate, and mental status (table 1).

In HHS, there is little or no ketoacid accumulation, the serum glucose concentration frequently exceeds 1000 mg/dL (56 mmol/L), the plasma osmolality may reach 380 mosmol/kg, and neurologic abnormalities are frequently present (including coma in 25 to 50 percent of cases) [2,3,5]. Most patients with HHS have an admission pH >7.30, a serum bicarbonate >20 meq/L, a serum glucose >600 mg/dL (33.3 mmol/L), and test negative for ketones in serum and urine, although mild ketonemia may be present.

DKA is characterized by the triad of hyperglycemia, anion gap metabolic acidosis, and ketonemia. Metabolic acidosis is often the major finding. The serum glucose concentration is usually greater than 500 mg/dL (27.8 mmol/L) and less than 800 mg/dL (44.4 mmol/L) [2,6]. However, serum glucose concentrations may exceed 900 mg/dL (50 mmol/L) in patients with DKA who are comatose [7]. In certain instances, such as DKA in the setting of starvation or pregnancy, or treatment with insulin prior to arrival in the emergency department, the glucose may be only mildly elevated. Factors that contribute to the lesser degree of hyperglycemia in DKA, compared with HHS, are discussed below. (See 'Serum glucose' below.)

                         

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Dec 20, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th, McGraw-Hill, New York 2001. p.809-815.
  2. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine (Baltimore) 1972; 51:73.
  3. Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739.
  4. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32:1335.
  5. Daugirdas JT, Kronfol NO, Tzamaloukas AH, Ing TS. Hyperosmolar coma: cellular dehydration and the serum sodium concentration. Ann Intern Med 1989; 110:855.
  6. Fulop M, Tannenbaum H, Dreyer N. Ketotic hyperosmolar coma. Lancet 1973; 2:635.
  7. Morris LR, Kitabchi AE. Efficacy of low-dose insulin therapy for severely obtunded patients in diabetic ketoacidosis. Diabetes Care 1980; 3:53.
  8. Wachtel TJ. The diabetic hyperosmolar state. Clin Geriatr Med 1990; 6:797.
  9. Szeto CC, Li KY, Ko GT, et al. Acromegaly in a woman presenting with diabetic ketoacidosis and insulin resistance. Int J Clin Pract 1997; 51:476.
  10. Kitabchi AE, Fisher JN. Insulin therapy of diabetic ketoacidosis: Physiologic versus pharmacologic doses of insulin and their routes of administration. In: Handbook of Diabetes Mellitus, Brownlee M (Ed), Garland ATPM Press, New York 1981. p.95.
  11. Kitabchi AE, Razavi L.Hyperglycemic Crises: Diabetic Ketoacidosis (DKA), And Hyperglycemic Hyperosmolar State (HHS). In: http://www.endotext.org/diabetes/diabetes24/diabetesframe24.htm (Accessed on January 30, 2013).
  12. Randall L, Begovic J, Hudson M, et al. Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Diabetes Care 2011; 34:1891.
  13. Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the diabetic hyperosmolar state. J Am Geriatr Soc 1987; 35:737.
  14. Wachtel TJ, Tetu-Mouradjian LM, Goldman DL, et al. Hyperosmolarity and acidosis in diabetes mellitus: a three-year experience in Rhode Island. J Gen Intern Med 1991; 6:495.
  15. Kitabchi AE, Murphy MB. Consequences of insulin deficiency. In: Atlas of Diabetes, 4th, Skyler J. (Ed), Springer US, New York 2012. p.39.
  16. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005; 19 Suppl 1:1.
  17. Warner EA, Greene GS, Buchsbaum MS, et al. Diabetic ketoacidosis associated with cocaine use. Arch Intern Med 1998; 158:1799.
  18. Nyenwe EA, Loganathan RS, Blum S, et al. Active use of cocaine: an independent risk factor for recurrent diabetic ketoacidosis in a city hospital. Endocr Pract 2007; 13:22.
  19. Polonsky WH, Anderson BJ, Lohrer PA, et al. Insulin omission in women with IDDM. Diabetes Care 1994; 17:1178.
  20. Umpierrez GE, Kelly JP, Navarrete JE, et al. Hyperglycemic crises in urban blacks. Arch Intern Med 1997; 157:669.
  21. Peden NR, Braaten JT, McKendry JB. Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion. Diabetes Care 1984; 7:1.
  22. Weissberg-Benchell J, Antisdel-Lomaglio J, Seshadri R. Insulin pump therapy: a meta-analysis. Diabetes Care 2003; 26:1079.
  23. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin North Am 1995; 79:39.
  24. Maccario M. Neurological dysfunction associated with nonketotic hyperglycemia. Arch Neurol 1968; 19:525.
  25. Guisado R, Arieff AI. Neurologic manifestations of diabetic comas: correlation with biochemical alterations in the brain. Metabolism 1975; 24:665.
  26. Lavin PJ. Hyperglycemic hemianopia: a reversible complication of non-ketotic hyperglycemia. Neurology 2005; 65:616.
  27. Harden CL, Rosenbaum DH, Daras M. Hyperglycemia presenting with occipital seizures. Epilepsia 1991; 32:215.
  28. Nyenwe EA, Razavi LN, Kitabchi AE, et al. Acidosis: the prime determinant of depressed sensorium in diabetic ketoacidosis. Diabetes Care 2010; 33:1837.
  29. DeFronzo RA, Matzuda M, Barret E. Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev 1994; 2:209.
  30. Al-Kudsi RR, Daugirdas JT, Ing TS, et al. Extreme hyperglycemia in dialysis patients. Clin Nephrol 1982; 17:228.
  31. Popli S, Leehey DJ, Daugirdas JT, et al. Asymptomatic, nonketotic, severe hyperglycemia with hyponatremia. Arch Intern Med 1990; 150:1962.
  32. Malone ML, Gennis V, Goodwin JS. Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc 1992; 40:1100.
  33. Umpierrez G, Freire AX. Abdominal pain in patients with hyperglycemic crises. J Crit Care 2002; 17:63.
  34. Munro JF, Campbell IW, McCuish AC, Duncan LJ. Euglycaemic diabetic ketoacidosis. Br Med J 1973; 2:578.
  35. Burge MR, Hardy KJ, Schade DS. Short-term fasting is a mechanism for the development of euglycemic ketoacidosis during periods of insulin deficiency. J Clin Endocrinol Metab 1993; 76:1192.
  36. Eisenbarth GS, Polonsky KS, Buse JB. Type 1 diabetes mellitus: Acute diabetic emergencies: Diabetic ketoacidosis. In: Williams Textbook of Endocrinology, Larsen PR, Kronenberg HM, Melmed S, Polonsky KS (Eds), Elsevier Science, Philadelphia 2003. p.1500.
  37. Marliss EB, Ohman JL Jr, Aoki TT, Kozak GP. Altered redox state obscuring ketoacidosis in diabetic patients with lactic acidosis. N Engl J Med 1970; 283:978.
  38. Narins RG, Jones ER, Stom MC, et al. Diagnostic strategies in disorders of fluid, electrolyte and acid-base homeostasis. Am J Med 1982; 72:496.
  39. Porter WH, Yao HH, Karounos DG. Laboratory and clinical evaluation of assays for beta-hydroxybutyrate. Am J Clin Pathol 1997; 107:353.
  40. Fulop M, Murthy V, Michilli A, et al. Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med 1999; 159:381.
  41. Csako G, Elin RJ. Unrecognized false-positive ketones from drugs containing free-sulfhydryl group(s). JAMA 1993; 269:1634.
  42. Adrogué HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-base homeostasis re-evaluated. Kidney Int 1984; 25:591.
  43. Owen OE, Licht JH, Sapir DG. Renal function and effects of partial rehydration during diabetic ketoacidosis. Diabetes 1981; 30:510.
  44. Fulop M. The treatment of severely uncontrolled diabetes mellitus. Adv Intern Med 1984; 29:327.
  45. Adrogué HJ, Wilson H, Boyd AE 3rd, et al. Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med 1982; 307:1603.
  46. Oh MS, Carroll HJ, Goldstein DA, Fein IA. Hyperchloremic acidosis during the recovery phase of diabetic ketosis. Ann Intern Med 1978; 89:925.
  47. Katz MA. Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression. N Engl J Med 1973; 289:843.
  48. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med 1999; 106:399.
  49. Phillips PA, Bretherton M, Johnston CI, Gray L. Reduced osmotic thirst in healthy elderly men. Am J Physiol 1991; 261:R166.
  50. Adrogué HJ, Lederer ED, Suki WN, Eknoyan G. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine (Baltimore) 1986; 65:163.
  51. Khardori R, Soler NG. Hyperosmolar hyperglycemic nonketotic syndrome. Report of 22 cases and brief review. Am J Med 1984; 77:899.
  52. Kaminska ES, Pourmotabbed G. Spurious laboratory values in diabetic ketoacidosis and hyperlipidemia. Am J Emerg Med 1993; 11:77.
  53. Rumbak MJ, Hughes TA, Kitabchi AE. Pseudonormoglycemia in diabetic ketoacidosis with elevated triglycerides. Am J Emerg Med 1991; 9:61.
  54. Kreisberg RA. Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment. Ann Intern Med 1978; 88:681.
  55. Abramson E, Arky R. Diabetic acidosis with initial hypokalemia. Therapeutic implications. JAMA 1966; 196:401.
  56. Kitabchi AE, Young R, Sacks H, Morris L. Diabetic ketoacidosis: reappraisal of therapeutic approach. Annu Rev Med 1979; 30:339.
  57. Atchley DW, Loeb RF, Richards DW, et al. ON DIABETIC ACIDOSIS: A Detailed Study of Electrolyte Balances Following the Withdrawal and Reestablishment of Insulin Therapy. J Clin Invest 1933; 12:297.
  58. Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med 1981; 71:456.
  59. Fulop M. Serum potassium in lactic acidosis and ketoacidosis. N Engl J Med 1979; 300:1087.
  60. Adrogué HJ, Chap Z, Ishida T, Field JB. Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs. J Clin Invest 1985; 75:798.
  61. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med 1985; 79:571.
  62. Yadav D, Nair S, Norkus EP, Pitchumoni CS. Nonspecific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: incidence and correlation with biochemical abnormalities. Am J Gastroenterol 2000; 95:3123.
  63. Warshaw AL, Feller ER, Lee KH. On the cause of raised serum-amylase in diabetic ketoacidosis. Lancet 1977; 1:929.
  64. Vinicor F, Lehrner LM, Karn RC, Merritt AD. Hyperamylasemia in diabetic ketoacidosis: sources and significance. Ann Intern Med 1979; 91:200.
  65. Vantyghem MC, Haye S, Balduyck M, et al. Changes in serum amylase, lipase and leukocyte elastase during diabetic ketoacidosis and poorly controlled diabetes. Acta Diabetol 1999; 36:39.
  66. Kjaergaard JJ, Salling N, Magid E, Ditzel J. Serum amylase during recovery from diabetic ketoacidosis. Diabete Metab 1984; 10:25.
  67. Nair S, Yadav D, Pitchumoni CS. Association of diabetic ketoacidosis and acute pancreatitis: observations in 100 consecutive episodes of DKA. Am J Gastroenterol 2000; 95:2795.
  68. Stentz FB, Umpierrez GE, Cuervo R, Kitabchi AE. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 2004; 53:2079.
  69. Razavi, L, Taheri, E, Larijani, B, et al. Catecholamine-induced leukocytosis in acute hypoglycemic stress. J Investig Med 2007; 55:S262.
  70. Slovis CM, Mork VG, Slovis RJ, Bain RP. Diabetic ketoacidosis and infection: leukocyte count and differential as early predictors of serious infection. Am J Emerg Med 1987; 5:1.
  71. Weidman SW, Ragland JB, Fisher JN Jr, et al. Effects of insulin on plasma lipoproteins in diabetic ketoacidosis: evidence for a change in high density lipoprotein composition during treatment. J Lipid Res 1982; 23:171.
  72. Reichard GA Jr, Owen OE, Haff AC, et al. Ketone-body production and oxidation in fasting obese humans. J Clin Invest 1974; 53:508.
  73. Wrenn KD, Slovis CM, Minion GE, Rutkowski R. The syndrome of alcoholic ketoacidosis. Am J Med 1991; 91:119.
  74. Shah P, Isley WL. Ketoacidosis during a low-carbohydrate diet. N Engl J Med 2006; 354:97.