Advertisement

Acute Hyperglycemic Syndromes: Diabetic Ketoacidosis and the Hyperosmolar State

  • David Wing-Hang LamEmail author
  • Yun Feng
Reference work entry

Abstract

The patient, often a “repeat offender” who stops taking insulin, presents with increasing urination and thirst along with nausea, vomiting, abdominal pain, dehydration, weakness, and dizziness. The patient may become confused and slip into coma. The respiratory compensation that accompanies acidemia causes deep rapid (Kussmaul) breathing. The sweet smell of the volatile ketone body acetone signals the possibility of ketoacidosis. The treating physician seeks to reestablish normal physiology and restore the patient to normal function. Thankfully, treatment is remarkably straightforward and involves intravenous fluid, insulin, potassium, and vigilance.

Keywords

Diabetic Ketoacidosis Kussmaul Type 1 Diabetes Type 2 Diabetes Ketosis Hyperglycemia Anion Gap Metabolic Acidosis Free Fatty Acids ß-hydroxybutyrate Acetoacetate Cerebral Edema Hyperosmolar Hyperglycemia Syndrome 

Notes

Acknowledgments

This revision to Acute Hyperglycemic Syndromes: Diabetic Ketoacidosis and the Hyperosmolar State would not have been possible if not for the excellent initial chapter authored by Drs. Yun Feng and Adrienne M. Fleckman.

References

  1. 1.
    Maahs DM, Hermann JM, Holman N, Foster NC, Kapellen TM, Allgrove J, Schatz DA, Hofer SE, Campbell F, Steigleder-Schweiger C, Beck RW, Warner JT, Holl RW, National Paediatric Diabetes Audit and the Royal College of Paediatrics and the Child Health, the DPV Initiative, and the T1D Exchange Clinic Network. Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. Diabetes Care. 2015;38:1876–82.CrossRefPubMedGoogle Scholar
  2. 2.
    Pietropaolo M, Barinas-Mitchell E, Kuller LH. The heterogeneity of diabetes: unraveling a dispute: is systemic inflammation related to islet autoimmunity? Diabetes. 2007;56:1189–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Balasubramanyam A, Garza G, Rodriguez L, et al. Accuracy and predictive value of classification schemes for ketosis-prone diabetes. Diabetes Care. 2006;29:2575–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Klingensmith GJ, Connor CG, Ruedy KJ, Beck RW, Kollman C, Haro H, Wood JR, Lee JM, Willi SM, Cengiz E, Tamborlane WV. Presentation of youth with type 2 diabetes in the pediatric diabetes consortium. Pediatr Diabetes. 2015. doi: 10.1111/pedi.12281. [Epub ahead of print] PMID: 25951940Google Scholar
  5. 5.
    Rodríguez-Gutiérrez R, Camara-Lemarroy CR, Quintanilla-Flores DL, González-Moreno EI, González-Chavez JM, Lavalle-González FJ, González-Gonzalez JG, Caballero AE. Severe ketoacidosis (pH ≤ 6.9) in type 2 diabetes: more frequent and less ominous than previously thought. Biomed Res Int. 2015;2015:134780. Epub 2015 Jun 21. PMID: 26180779Google Scholar
  6. 6.
    Valabhji J, Watson M, Cox J, Poulter C, Elwig C, Elkeles RS. Type 2 diabetes presenting as diabetic ketoacidosis in adolescence. Diabet Med. 2003;20:416–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Umpierrez GE, Woo W, Hagopian WA, et al. Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis. Diabetes Care. 1999;22:1517–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Dabelea D, Rewers A, Stafford JM, Standiford DA, Lawrence JM, Saydah S, Imperatore G, D’Agostino Jr RB, Mayer-Davis EJ, Pihoker C, Group SfDiYS. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014;133:e938–45.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Usher-Smith JA, Thompson MJ, Sharp SJ, Walter FM. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011;343:d4092.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fleckman AM. Diabetic ketoacidosis. Endocrinol Metab Clin N Am. 1993;22:181–207.Google Scholar
  11. 11.
    Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(12):2739–48.CrossRefPubMedGoogle Scholar
  12. 12.
    Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century. Lancet. 2008;372:892.CrossRefPubMedGoogle Scholar
  13. 13.
    Davis SN, Umpierrez GE. Diabetic ketoacidosis in type 2 diabetes mellitus – pathophysiology and clinical presentation. Nat Clin Pract Endocrinol Metab. 2007;3(11):730–1.CrossRefPubMedGoogle Scholar
  14. 14.
    Cooper GM, Hausman RE. The cell: a molecular approach. 4th ed. Washington, DC: ASM Press; 2007. p. 73–102, 433–71.Google Scholar
  15. 15.
    Nelson DL, Cox MM. Lehninger principles of biochemistry. 4th ed. New York: Freeman; 2005, Chapter 14-1, Glycolysis; Chapter 17, Fatty acid catabolism; Chapter 23.2 Tissue-specific metabolism.Google Scholar
  16. 16.
    DeFronzo RA, Matsuda M, Barrett EJ. Diabetic ketoacidosis. Diabetes Rev. 1994;2:209–38.Google Scholar
  17. 17.
    Mullins GR, Wang L, Raje V, Sherwood SG, Grande RC, Boroda S, Eaton JM, Blancquaert S, Roger PP, Leitinger N, Harris TE. Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes. Proc Natl Acad Sci U S A. 2014;111:17450–5.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ottosson M, Lönnroth P, Björntorp P, et al. Effects of cortisol and growth hormone on lipolysis in human adipose tissue. J Clin Endocrinol Metab. 2000;85:799–803.PubMedGoogle Scholar
  19. 19.
    Seckl JR, Walker BR. Minireview: 11beta-hydroxysteroid dehydrogenase type 1 – a tissue-specific amplifier of glucocorticoid action. Endocrinol. 2001;142:1371–6.CrossRefGoogle Scholar
  20. 20.
    Gaboriaud-Kolar N, Skaltsounis AL. Glycogen phosphorylase inhibitors: a patent review (2008–2012). Expert Opin Ther Pat. 2013;23:1017–32.CrossRefPubMedGoogle Scholar
  21. 21.
    Zammit VA. Regulation of ketone body metabolism. Diabetes Rev. 1994;2:132–55.Google Scholar
  22. 22.
    Kreisberg RA. Lactate homeostasis and lactic acidosis. Ann Intern Med. 1980;92(2 Pt 1):227–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/Metab Res Rev. 1999;15:412–26.CrossRefGoogle Scholar
  24. 24.
    Berg JM, Tymoczko JL, Stryer L. Biochemistry. 6th ed. New York: Freeman; 2007. p. 632–3, Chapter 22, Fatty acid metabolism: ketone bodies are a major fuel in some tissues.Google Scholar
  25. 25.
    Randall L, Begovic J, Hudson M, Smiley D, Peng L, Pitre N, Umpierrez D, Umpierrez G. Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Diabetes Care. 2011;34:1891–6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Maldonado MR, Chong ER, Oehl MA, Balasubramanyam A. Economic impact of diabetic ketoacidosis in a multiethnic indigent population: analysis of costs based on the precipitating cause. Diabetes Care. 2003;26:1265–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Jin H, Meyer JM, Jeste DV. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases. Ann Clin Psychiatry. 2002;14(1):59–64.CrossRefPubMedGoogle Scholar
  28. 28.
    Ramaswamy K, Masand PS, Nasrallah HA. Do certain atypical antipsychotics increase the risk of diabetes? A critical review of 17 pharmacoepidemiologic studies. Ann Clin Psychiatry. 2006;18(3):183–94.CrossRefPubMedGoogle Scholar
  29. 29.
    Imagawa A, Hanafusa T, Miyagawa JI, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. N Engl J Med. 2000;342:301–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Yoon JW, Austin M, Onodera T, et al. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med. 1979;300(21):1173–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Chen LK, Chou YC, Tsai ST, et al. Hepatitis C virus infection-related type 1 diabetes mellitus. Diabetic Med. 2005;22(3):340–3.CrossRefPubMedGoogle Scholar
  32. 32.
    Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003;26:510–3.CrossRefPubMedGoogle Scholar
  33. 33.
    Muller LM, Gorter KJ, Hak E, Goudzwaard WL, Schellevis FG, Hoepelman AI, Rutten GE. Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin Infect Dis. 2005;41:281–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Koh GC, Peacock SJ, van der Poll T, Wiersinga WJ. The impact of diabetes on the pathogenesis of sepsis. Eur J Clin Microbiol Infect Dis. 2012;31:379–88.CrossRefPubMedGoogle Scholar
  35. 35.
    Katz MA. Hyperglycemia-induced hyponatremia – calculation of expected serum sodium depression. N Engl J Med. 1973;289(16):843–4.CrossRefPubMedGoogle Scholar
  36. 36.
    Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999;106:399–403.CrossRefPubMedGoogle Scholar
  37. 37.
    Brandenburg MA, Dire DJ. Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis. Ann Emerg Med. 1998;31:459–65.CrossRefPubMedGoogle Scholar
  38. 38.
    Fulop M, Murthy V, Michili A, et al. Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med. 1999;159:381–4.CrossRefPubMedGoogle Scholar
  39. 39.
    White NH. Diabetic ketoacidosis in children. Endocrinol Metab Clin. 2000;29:657–82.CrossRefGoogle Scholar
  40. 40.
    Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents. Diabetes Care. 2006;29:1150–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Adrogué HJ, Barrero J, Eknoyan G. Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. JAMA. 1989;262:2108–13.CrossRefPubMedGoogle Scholar
  42. 42.
    Rave K, Nosek L, Posner J, et al. Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes – results of a hyperglycaemic glucose clamp study. Nephrol Dial Transplant. 2006;21:2166–71.CrossRefPubMedGoogle Scholar
  43. 43.
    Kawata H, Inui D, Ohto J, et al. The use of continuous hemodiafiltration in a patient with diabetic ketoacidosis. J Anesth. 2006;20(2):129–31.CrossRefPubMedGoogle Scholar
  44. 44.
    Kaufman FR. Diabetes in children and adolescents: areas of controversy. Med Clin N Am. 1998;82:721–38.CrossRefPubMedGoogle Scholar
  45. 45.
    Muir A. Cerebral edema in diabetic ketoacidosis: a look beyond rehydration. J Clin Endocrinol Metab. 2000;85:509–13.CrossRefGoogle Scholar
  46. 46.
    Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990–96. Arch Dis Child. 1999;81:318–23.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr. 2005;146:688–92.CrossRefPubMedGoogle Scholar
  48. 48.
    Glaser N. Cerebral injury and cerebral edema in children with diabetic ketoacidosis: could cerebral ischemia and reperfusion injury be involved? Pediatr Diabetes. 2009;10:534–41.CrossRefPubMedGoogle Scholar
  49. 49.
    Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med. 2001;344:264–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Isales CM, Min L, Hoffman WH. Acetoacetate and beta-hydroxybutyrate differentially regulate endothelin-1 and vascular endothelial growth factor in mouse brain microvascular endothelial cells. J Diabet Complications. 1999;13:91–7.CrossRefGoogle Scholar
  51. 51.
    Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999;21:721–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Wagner A, Risse A, Brill HL, et al. Therapy of severe diabetic ketoacidosis: zero-mortality under very-low-dose insulin application. Diabetes Care. 1999;22:674–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Ceron M, Robalino G. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care. 2009;32:1164–9.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care. 2008;31:2081–5.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Goyal N, Miller JB, Sankey SS, Mossallam U. Utility of initial bolus insulin in the treatment of diabetic ketoacidosis. J Emerg Med. 2010;38:422–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Vincent M, Nobecourt E. Treatment of diabetic ketoacidosis with subcutaneous insulin lispro: a review of the current evidence from clinical studies. Diabetes Metab. 2013;39:299–305.CrossRefPubMedGoogle Scholar
  57. 57.
    Weiner ID, Wingo CS. Hypokalemia – consequences, causes, and correction. J Am Soc Nephrol. 1997;8:1179–88.PubMedGoogle Scholar
  58. 58.
    Tattersall RB. A paper which changed clinical practice (slowly). Jacob Holler on potassium deficiency in diabetic acidosis (1946). Diabet Med. 1999;16:978–84.CrossRefPubMedGoogle Scholar
  59. 59.
    Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. 1999;27:2690–3.CrossRefPubMedGoogle Scholar
  60. 60.
    Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med. 1986;105:836–40.CrossRefPubMedGoogle Scholar
  61. 61.
    Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med. 1983;75:263–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Malone ML, Gennis V, Goodwin JS. Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc. 1992;40:1100–4.CrossRefPubMedGoogle Scholar
  63. 63.
    Ezeani I, Eregie A, Ogedengbe O. Treatment outcome and prognostic indices in patients with hyperglycemic emergencies. Diabetes Metab Syndr Obes. 2013;6:303–7.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Decourcey DD, Steil GM, Wypij D, Agus MS. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality*. Pediatr Crit Care Med. 2013;14:694–700.CrossRefPubMedGoogle Scholar
  65. 65.
    Azevedo LC, Choi H, Simmonds K, Davidow J, Bagshaw SM. Incidence and long-term outcomes of critically ill adult patients with moderate-to-severe diabetic ketoacidosis: retrospective matched cohort study. J Crit Care. 2014;29:971–7.CrossRefPubMedGoogle Scholar
  66. 66.
    Bialo SR, Agrawal S, Boney CM, Quintos JB. Rare complications of pediatric diabetic ketoacidosis. World J Diabetes. 2015;6:167–74.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Wang LM, Tsai ST, Ho LT, Hu SC, Lee CH. Rhabdomyolysis in diabetic emergencies. Diabetes Res Clin Pract. 1994;26:209–14.CrossRefPubMedGoogle Scholar
  68. 68.
    Hoffman WH, Locksmith JP, Burton EM, et al. Interstitial pulmonary edema in children and adolescents with diabetic ketoacidosis. J Diabet Complications. 1998;12:314–20.CrossRefGoogle Scholar
  69. 69.
    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;36:39–44.CrossRefPubMedGoogle Scholar
  70. 70.
    Nair S, Pitchumoni CS. Diabetic ketoacidosis, hyperlipidemia, and acute pancreatitis: the enigmatic triangle. Am J Gastroenterol. 1997;92:1560–1.PubMedGoogle Scholar
  71. 71.
    Nair S, Yadav D, Pitchumoni CS. Association of diabetic ketoacidosis and acute pancreatitis: observations in 100 consecutive episodes of DKA. Am J Gastroenterol. 2000;95:2795–800.CrossRefPubMedGoogle Scholar
  72. 72.
    Fulop M, Eder H. Severe hypertriglyceridemia in diabetic ketosis. Am J Med Sci. 1990;300:361–5.CrossRefPubMedGoogle Scholar
  73. 73.
    Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab. 1983;57:177–80.CrossRefPubMedGoogle Scholar
  74. 74.
    Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118:1094–101.CrossRefPubMedGoogle Scholar
  75. 75.
    Mégarbane B, Guerrier G, Blancher A, et al. A possible hypophosphatemia-induced, life-threatening encephalopathy in diabetic ketoacidosis: a case report. Am J Med Sci. 2007;333(6):384–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Podar T, Solntsev A, Reunanen A, et al. Mortality in patients with childhood-onset type 1 diabetes in Finland, Estonia, and Lithuania: follow-up of nationwide cohorts. Diabetes Care. 2000;23:290–4.CrossRefPubMedGoogle Scholar
  77. 77.
    Lipton R, Good G, Mikhailov T, et al. Ethnic differences in mortality from insulin-dependent diabetes mellitus among people less than 25 years of age. Pediatrics. 1999;103:952–6.CrossRefPubMedGoogle Scholar
  78. 78.
    Shrestha SS, Zhang P, Barker L, Imperatore G. Medical expenditures associated with diabetes acute complications in privately insured U.S. youth. Diabetes Care. 2010;33:2617–22.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Icks A, Strassburger K, Baechle C, Rosenbauer J, Giani G, Beyer P, Holl RW. Frequency and cost of diabetic ketoacidosis in Germany – study in 12,001 paediatric patients. Exp Clin Endocrinol Diabetes. 2013;121:58–9.PubMedGoogle Scholar
  80. 80.
    Vanelli M, Chiari G, Ghizzoni L, et al. 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.CrossRefPubMedGoogle Scholar
  81. 81.
    Bonadio WA, Gutzeit MF, Losek JD, et al. Outpatient management of diabetic ketoacidosis. Am J Dis Child. 1988;142:448–50.CrossRefPubMedGoogle Scholar
  82. 82.
    Marinac JS, Jesa L. Using a severity of illness scoring system to assess intensive care unit admissions for diabetic ketoacidosis. Crit Care Med. 2000;28:2238–41.CrossRefPubMedGoogle Scholar
  83. 83.
    Levetan CS, Passaro MD, Jablonski KA, et al. Effect of physician specialty on outcomes in diabetic ketoacidosis. Diabetes Care. 1999;22:1790–5.CrossRefPubMedGoogle Scholar
  84. 84.
    Thawabi M, Studyvin S. Euglycemic diabetic ketoacidosis, a misleading presentation of diabetic ketoacidosis. N Am J Med Sci. 2015;7:291–4.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Chico M, Levine SN, Lewis DF. Normoglycemic diabetic ketoacidosis in pregnancy. J Perinatol. 2008;28:310–2.CrossRefPubMedGoogle Scholar
  86. 86.
    Cullen MT, Reece EA, Homko CJ, et al. The changing presentations of diabetic ketoacidosis during pregnancy. Am J Perinatol. 1996;13(7):449–51.CrossRefPubMedGoogle Scholar
  87. 87.
    Bas VN, Uytun S, Torun YA. Diabetic euglycemic ketoacidosis in newly diagnosed type 1 diabetes mellitus during Ramadan fasting. J Pediatr Endocrinol Metab. 2015;28:333–5.PubMedGoogle Scholar
  88. 88.
    Winter WE, Maclaren NK, Riley WJ, et al. Maturity-onset diabetes of youth in black Americans. N Engl J Med. 1987;316:285–91.CrossRefPubMedGoogle Scholar
  89. 89.
    Banerji MA, Chaiken RL, Huey H, et al. GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. Diabetes. 1994;43:741–5.CrossRefPubMedGoogle Scholar
  90. 90.
    Banerji MA, Chaiken RL, Lebovitz HE. Long-term normoglycemic remission in black newly diagnosed NIDDM subjects. Diabetes. 1996;45:337–41.CrossRefPubMedGoogle Scholar
  91. 91.
    Matz R. Management of the hyperosmolar hyperglycemic syndrome. Am Fam Physician. 1999;60:1468–76.PubMedGoogle Scholar
  92. 92.
    Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32:1335–43.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Chupin M, Charbonnel B, Chupin F. C-peptide blood levels in keto-acidosis and in hyperosmolar non-ketotic diabetic coma. Acta Diabetol Lat. 1981;18:123–8.CrossRefPubMedGoogle Scholar
  94. 94.
    Fulop M, Tannenbaum H, Dreyer N. Ketotic hyperosmolar coma. Lancet. 1973;2:635–9.CrossRefPubMedGoogle Scholar
  95. 95.
    Daugirdas JT, Kronfol NO, Tzamaloukas AH, et al. Hyperosmolar coma: cellular dehydration and the serum sodium concentration. Ann Intern Med. 1989;110:855–7.CrossRefPubMedGoogle Scholar
  96. 96.
    Cochran JB, Walters S, Losek JD. Pediatric hyperglycemic hyperosmolar syndrome: diagnostic difficulties and high mortality rate. Am J Emerg Med. 2006;24:297–301.CrossRefPubMedGoogle Scholar
  97. 97.
    Bagdure D, Rewers A, Campagna E, Sills MR. Epidemiology of hyperglycemic hyperosmolar syndrome in children hospitalized in USA. Pediatr Diabetes. 2013;14:18–24.CrossRefPubMedGoogle Scholar
  98. 98.
    Ileri NS, Buyukasik Y, Karaahmetoglu S, et al. Evaluation of the haemostatic system during ketoacidotic deterioration of diabetes mellitus. Haemostasis. 1999;29:318–25.PubMedGoogle Scholar
  99. 99.
    Balasubramanyam A, Zern JW, Hyman DJ, et al. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity. Arch Intern Med. 1999;159:2317–22.CrossRefPubMedGoogle Scholar

Recommended Websites

  1. Medline Plus. Diabetic ketoacidosis. 2014. https://www.nlm.nih.gov/medlineplus/ency/article/000320.htm. Accessed 30 Sept 2015.
  2. eMedicine from WebMD. Diabetic ketoacidosis. 2015. http://emedicine.medscape.com/article/118361-overview. Accessed 30 Sept 2015.

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Medicine, Division of EndocrinologyDiabetes and Bone Disease, Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Division of Endocrinology and MetabolismBeth Israel Medical Center, Albert Einstein College of MedicineNew YorkUSA

Personalised recommendations