History

Insidious increased thirst (ie, polydipsia) and urination (ie, polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA). Malaise, generalized weakness, and fatigability also can present as symptoms of DKA.

Nausea and vomiting usually occur and may be associated with diffuse abdominal pain, decreased appetite, and anorexia. A history of rapid weight loss is a symptom in patients who are newly diagnosed with type 1 diabetes.

Patients may present with a history of failure to comply with insulin therapy or missed insulin injections due to vomiting or psychological reasons. Decreased perspiration is another possible symptom of DKA.

Altered consciousness in the form of mild disorientation or confusion can occur. Although frank coma is uncommon, it may occur when the condition is neglected or if dehydration or acidosis is severe.

Among the symptoms of DKA associated with possible intercurrent infection are fever, dysuria, coughing, malaise, chills, chest pain, shortness of breath, and arthralgia. Acute chest pain or palpitation may occur in association with myocardial infarction. Painless infarction is not uncommon in patients with diabetes and should always be suspected in elderly patients.

A study by Crossen et al indicated that in children with type 1 diabetes, those who have had a recent emergency department visit and have undergone a long period without visiting an endocrinologist are more likely to develop DKA. The study included 5263 pediatric patients with type 1 diabetes.^[21]

Physical Examination

General signs of diabetic ketoacidosis (DKA) may include the following:

Ill appearance
Dry skin
Labored respiration
Dry mucous membranes
Decreased skin turgor
Decreased reflexes
Characteristic acetone (ketotic) breath odor

Effects on vital signs that are related to DKA may include the following:

Tachycardia
Hypotension
Tachypnea
Hypothermia
Fever, if infection is present

Specific signs of DKA may include the following:

Confusion
Coma
Abdominal tenderness

The physical examination should also include detection of the signs of possible intercurrent illnesses such as myocardial infarction, urinary tract infection, pneumonia, and perinephric abscess. Search for signs of infection is mandatory in all cases.

Noticing that the body temperature may be within the reference range or low, even in the presence of intercurrent infection, is particularly important.

Signs and Symptoms of Hyperglycemia, Acidosis, and Dehydration

Symptoms of hyperglycemia associated with diabetic ketoacidosis may include thirst, polyuria, polydipsia, and nocturia.

Signs of acidosis may include rapid, shallow breathing (sigh breathing) that, as the acidosis grows more severe, becomes slower, deeper, and labored (air hunger), as well as abdominal tenderness and disturbance of consciousness. Although these signs are not usual in all cases of diabetic ketoacidosis (DKA), their presence signifies a severe form of DKA. The breath has a fruity smell.

Signs of dehydration include a weak and rapid pulse, dry tongue and skin, hypotension, and increased capillary refill time.

Emphasizing that no direct correlation exists between the degree of acidosis, hyperglycemia, and the disturbances in the level of consciousness is important.

Complications Associated with DKA

Complications associated with DKA include sepsis and diffuse ischemic processes. Other associated complications include the following:

CVT
Myocardial infarction
DVT
Acute gastric dilatation
Erosive gastritis
Late hypoglycemia
Respiratory distress
Infection (most commonly, urinary tract infections)
Hypophosphatemia
Mucormycosis
Cerebrovascular accident

A prospective study by Jessup et al indicated that in pediatric patients with new-onset type 1 diabetes, those with severe, but uncomplicated, DKA tended to display lower cognitive functioning following correction of the DKA than did age-matched patients without DKA. The investigators suggested that DKA and/or its treatment produces a neuronal insult that causes “acute and possibly long-term cognitive deficits.”^[22]

Differential Diagnoses

Glaser NS, Marcin JP, Wootton-Gorges SL, et al. Correlation of clinical and biochemical findings with diabetic ketoacidosis-related cerebral edema in children using magnetic resonance diffusion-weighted imaging. J Pediatr. 2008 Jun 25. [QxMD MEDLINE Link].
Umpierrez GE, Jones S, Smiley D, et al. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care. 2009 Jul. 32(7):1164-9. [QxMD MEDLINE Link]. [Full Text].
Herrington WG, Nye HJ, Hammersley MS, Watkinson PJ. Are arterial and venous samples clinically equivalent for the estimation of pH, serum bicarbonate and potassium concentration in critically ill patients?. Diabet Med. 2012 Jan. 29(1):32-5. [QxMD MEDLINE Link].
Mrozik LT, Yung M. Hyperchloraemic metabolic acidosis slows recovery in children with diabetic ketoacidosis: a retrospective audit. Aust Crit Care. 2009 Jun 26. [QxMD MEDLINE Link].
Bowden SA, Duck MM, Hoffman RP. Young children (12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor. Pediatr Diabetes. 2008 Jun. 9(3 Pt 1):197-201. [QxMD MEDLINE Link].
Potenza M, Via MA, Yanagisawa RT. Excess thyroid hormone and carbohydrate metabolism. Endocr Pract. 2009 May-Jun. 15(3):254-62. [QxMD MEDLINE Link].
Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab. 2015 Aug. 100 (8):2849-52. [QxMD MEDLINE Link].
Tucker ME. More Guidance on 'Vulnerable Subgroup' With Diabetes and COVID-19. Medscape Medical News. 2020 Apr 28. [Full Text].
Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun. 8 (6):546-50. [QxMD MEDLINE Link]. [Full Text].
Vitale, RJ, Valtis YK, McDonnell ME, Palermo NE, Fisher NDL. Euglycemic diabetic ketoacidosis with COVID-19 infection in patients with type 2 diabetes taking SGLT2 inhibitors. AACE Clin Case Rep. 2020 Dec 28. [Full Text].
Tucker ME. Further Warning on SGLT2 Inhibitor Use and DKA Risk in COVID-19. Medscape Medical News. 2021 Jan 18. [Full Text].
Zhong VW, Juhaeri J, Mayer-Davis EJ. Trends in Hospital Admission for Diabetic Ketoacidosis in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study. Diabetes Care. 2018 Jan 31. 48 (4):87-9. [QxMD MEDLINE Link].
Zargar AH, Wani AI, Masoodi SR, et al. Causes of mortality in diabetes mellitus: data from a tertiary teaching hospital in India. Postgrad Med J. 2009 May. 85(1003):227-32. [QxMD MEDLINE Link].
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 Jul 7. 343:d4092. [QxMD MEDLINE Link].
Lee MH, Calder GL, Santamaria JD, MacIsaac RJ. Diabetic Ketoacidosis in Adult Patients: An Audit of Factors Influencing Time to Normalisation of Metabolic Parameters. Intern Med J. 2018 Jan 8. [QxMD MEDLINE Link].
Lin SF, Lin JD, Huang YY. Diabetic ketoacidosis: comparisons of patient characteristics, clinical presentations and outcomes today and 20 years ago. Chang Gung Med J. 2005 Jan. 28(1):24-30. [QxMD MEDLINE Link].
Hursh BE, Ronsley R, Islam N, Mammen C, Panagiotopoulos C. Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis. JAMA Pediatr. 2017 Mar 13. e170020. [QxMD MEDLINE Link].
Chen YL, Weng SF, Yang CY, Wang JJ, Tien KJ. Long-term risk of stroke in type 2 diabetes patients with diabetic ketoacidosis: A population-based, propensity score-matched, longitudinal follow-up study. Diabetes Metab. 2017 Jan 24. [QxMD MEDLINE Link].
Pugliese G, Zanuso S, Alessi E, et al. Self glucose monitoring and physical exercise in diabetes. Diabetes Metab Res Rev. 2009 Sep. 25 Suppl 1:S11-7. [QxMD MEDLINE Link].
Weber C, Kocher S, Neeser K, et al. Prevention of diabetic ketoacidosis and self-monitoring of ketone bodies: an overview. Curr Med Res Opin. 2009 May. 25(5):1197-207. [QxMD MEDLINE Link].
Crossen SS, Wilson DM, Saynina O, Sanders LM. Outpatient Care Preceding Hospitalization for Diabetic Ketoacidosis. Pediatrics. 2016 Jun. 137 (6):[QxMD MEDLINE Link].
Jessup AB, Grimley MB, Meyer E, et al. Effects of Diabetic Ketoacidosis on Visual and Verbal Neurocognitive Function in Young Patients Presenting with New-Onset Type 1 Diabetes. J Clin Res Pediatr Endocrinol. 2015 Sep. 7 (3):203-10. [QxMD MEDLINE Link]. [Full Text].
Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in diabetes. Diabetes Care. 2004 Jan. 27 Suppl 1:S94-102. [QxMD MEDLINE Link].
Arora S, Henderson SO, Long T, Menchine M. Diagnostic Accuracy of Point-of-Care Testing for Diabetic Ketoacidosis at Emergency-Department Triage: beta-Hydroxybutyrate versus the urine dipstick. Diabetes Care. 2011 Apr. 34(4):852-4. [QxMD MEDLINE Link]. [Full Text].
Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JA, Courtney CH, et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med. 2011 May. 28(5):508-15. [QxMD MEDLINE Link].
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults. March 2010. Available at http://www.diabetes.nhs.uk/document.php?o=1336. Accessed: June 27, 2011.
Wallace TM, Matthews DR. Recent advances in the monitoring and management of diabetic ketoacidosis. QJM. 2004 Dec. 97(12):773-80. [QxMD MEDLINE Link].
Ma OJ, Rush MD, Godfrey MM, Gaddis G. Arterial blood gas results rarely influence emergency physician management of patients with suspected diabetic ketoacidosis. Acad Emerg Med. 2003 Aug. 10(8):836-41. [QxMD MEDLINE Link].
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 Apr. 31(4):459-65. [QxMD MEDLINE Link].
Goyal N, Miller JB, Sankey SS, Mossallam U. Utility of initial bolus insulin in the treatment of diabetic ketoacidosis. J Emerg Med. 2010 May. 38(4):422-7. [QxMD MEDLINE Link].
[Guideline] Wolfsdorf J, Craig ME, Daneman D, Dunger D, Edge J, Lee WR, et al. Diabetic ketoacidosis. Pediatr Diabetes. 2007 Feb. 8(1):28-43. [QxMD MEDLINE Link].
Glaser NS, Wootton-Gorges SL, Buonocore MH, Marcin JP, Rewers A, Strain J, et al. Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatr Diabetes. 2006 Apr. 7(2):75-80. [QxMD MEDLINE Link].
Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification. Diabetes Care. 2004 Jul. 27(7):1541-6. [QxMD MEDLINE Link].
Hom J, Sinert R. Evidence-based emergency medicine/critically appraised topic. Is fluid therapy associated with cerebral edema in children with diabetic ketoacidosis?. Ann Emerg Med. 2008 Jul. 52(1):69-75.e1. [QxMD MEDLINE Link].
Bradley P, Tobias JD. An evaluation of the outside therapy of diabetic ketoacidosis in pediatric patients. Am J Ther. 2008 Nov-Dec. 15(6):516-9. [QxMD MEDLINE Link].
Chandu A, Macisaac RJ, Smith AC, Bach LA. Diabetic ketoacidosis secondary to dento-alveolar infection. Int J Oral Maxillofac Surg. 2002 Feb. 31(1):57-9. [QxMD MEDLINE Link].
Ai D, Roper TA, Riley JA. Diabetic ketoacidosis and clozapine. Postgrad Med J. 1998 Aug. 74(874):493-4. [QxMD MEDLINE Link].
Amemiya S. Constant infused glucose regimen during the recovery phase of diabetic ketoacidosis in children and adolescents with IDDM. Diabetes Care. 1998 Apr. 21(4):676-7. [QxMD MEDLINE Link].
Bohan JS. Chemical measurements in ketoacidosis. Arch Intern Med. 1999 Sep 27. 159(17):2089. [QxMD MEDLINE Link].
Brink SJ. Diabetic ketoacidosis: prevention, treatment and complications in children and adolescents. Diabetes Nutr Metab. 1999 Apr. 12(2):122-35. [QxMD MEDLINE Link].
Carroll MA, Yeomans ER. Diabetic ketoacidosis in pregnancy. Crit Care Med. 2005 Oct. 33(10 Suppl):S347-53. [QxMD MEDLINE Link].
Catalano C, Fabbian F, Di Landro D. Acute pulmonary oedema occurring in association with diabetic ketoacidosis in a diabetic patient with chronic renal failure. Nephrol Dial Transplant. 1998 Feb. 13(2):491-2. [QxMD MEDLINE Link].
Charfen MA, Fernández-Frackelton M. Diabetic ketoacidosis. Emerg Med Clin North Am. 2005 Aug. 23(3):609-28, vii. [QxMD MEDLINE Link].
Della Manna T, Steinmetz L, Campos PR, Farhat SC, Schvartsman C, Kuperman H. Subcutaneous use of a fast-acting insulin analog: an alternative treatment for pediatric patients with diabetic ketoacidosis. Diabetes Care. 2005 Aug. 28(8):1856-61. [QxMD MEDLINE Link].
Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child. 1999 Oct. 81(4):318-23. [QxMD MEDLINE Link].
Fearon DM, Steele DW. End-tidal carbon dioxide predicts the presence and severity of acidosis in children with diabetes. Acad Emerg Med. 2002 Dec. 9(12):1373-8. [QxMD MEDLINE Link].
Fisken RA. Severe diabetic ketoacidosis: the need for large doses of insulin. Diabet Med. 1999 Apr. 16(4):347-50. [QxMD MEDLINE Link].
Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001 Jan 25. 344(4):264-9. [QxMD MEDLINE Link].
Green SM, Rothrock SG, Ho JD, Gallant RD, Borger R, Thomas TL, et al. Failure of adjunctive bicarbonate to improve outcome in severe pediatric diabetic ketoacidosis. Ann Emerg Med. 1998 Jan. 31(1):41-8. [QxMD MEDLINE Link].
Grimberg A, Cerri RW, Satin-Smith M, Cohen P. The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management. J Pediatr. 1999 Mar. 134(3):376-8. [QxMD MEDLINE Link].
Guenette MD, Hahn M, Cohn TA, Teo C, Remington GJ. Atypical antipsychotics and diabetic ketoacidosis: a review. Psychopharmacology (Berl). 2013 Mar. 226(1):1-12. [QxMD MEDLINE Link].
Hjort U, Christensen JH. Diabetic ketoacidosis and compliance. Lancet. 1998 Feb 28. 351(9103):674-5. [QxMD MEDLINE Link].
Hoffman WH, Locksmith JP, Burton EM, et al. Interstitial pulmonary edema in children and adolescents with diabetic ketoacidosis. J Diabetes Complications. 12(6):314-20. [QxMD MEDLINE Link].
Kannan CR. Bicarbonate therapy in the management of severe diabetic ketoacidosis. Crit Care Med. 1999 Dec. 27(12):2833-4. [QxMD MEDLINE Link].
Kaufman FR, Halvorson M. The treatment and prevention of diabetic ketoacidosis in children and adolescents with type I diabetes mellitus. Pediatr Ann. 1999 Sep. 28(9):576-82. [QxMD MEDLINE Link].
Kaufman FR, Halvorson M, Fisher L, Pitukcheewanont P. Insulin pump therapy in type 1 pediatric patients. J Pediatr Endocrinol Metab. 1999. 12 Suppl 3:759-64. [QxMD MEDLINE Link].
Kitabchi AE, Nyenwe EA. Hyperglycemic crises in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 2006 Dec. 35(4):725-51, viii. [QxMD MEDLINE Link].
Kreshak A, Chen EH. Arterial blood gas analysis: are its values needed for the management of diabetic ketoacidosis?. Ann Emerg Med. 2005 May. 45(5):550-1. [QxMD MEDLINE Link].
Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999 Nov-Dec. 15(6):412-26. [QxMD MEDLINE Link].
Liss DS, Waller DA, Kennard BD, McIntire D, Capra P, Stephens J. Psychiatric illness and family support in children and adolescents with diabetic ketoacidosis: a controlled study. J Am Acad Child Adolesc Psychiatry. 1998 May. 37(5):536-44. [QxMD MEDLINE Link].
Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999 Oct. 21(4):721-7. [QxMD MEDLINE Link].
Martin SL, Hoffman WH, Marcus DM, Passmore GG, Dalton RR. Retinal vascular integrity following correction of diabetic ketoacidosis in children and adolescents. J Diabetes Complications. 2005 Jul-Aug. 19(4):233-7. [QxMD MEDLINE Link].
McDonnell CM, Pedreira CC, Vadamalayan B, Cameron FJ, Werther GA. Diabetic ketoacidosis, hyperosmolarity and hypernatremia: are high-carbohydrate drinks worsening initial presentation?. Pediatr Diabetes. 2005 Jun. 6(2):90-4. [QxMD MEDLINE Link].
Moller N, Foss AC, Gravholt CH, Mortensen UM, Poulsen SH, Mogensen CE. Myocardial injury with biomarker elevation in diabetic ketoacidosis. J Diabetes Complications. 2005 Nov-Dec. 19(6):361-3. [QxMD MEDLINE Link].
Newton CA, Raskin P. Diabetic ketoacidosis in type 1 and type 2 diabetes mellitus: clinical and biochemical differences. Arch Intern Med. 2004 Sep 27. 164(17):1925-31. [QxMD MEDLINE Link].
Paton RC, Sathiavageeswaran M. Severe diabetic ketoacidosis. Diabet Med. 1999 Oct. 16(10):884. [QxMD MEDLINE Link].
Reichel A, Rietzsch H, Kohler HJ, Pfutzner A, Gudat U, Schulze J. Cessation of insulin infusion at night-time during CSII-therapy: comparison of regular human insulin and insulin lispro. Exp Clin Endocrinol Diabetes. 1998. 106(3):168-72. [QxMD MEDLINE Link].
Smith CP, Firth D, Bennett S, Howard C, Chisholm P. Ketoacidosis occurring in newly diagnosed and established diabetic children. Acta Paediatr. 1998 May. 87(5):537-41. [QxMD MEDLINE Link].
Timmons JA, Myer P, Maturen A, et al. Use of beta-hydroxybutyric acid levels in the emergency department. Am J Ther. 1998 May. 5(3):159-63. [QxMD MEDLINE Link].
Umpierrez GE, Cuervo R, Karabell A, Latif K, Freire AX, Kitabchi AE. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 2004 Aug. 27(8):1873-8. [QxMD MEDLINE Link].
Umpierrez GE, Smiley D, Kitabchi AE. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med. 2006 Mar 7. 144(5):350-7. [QxMD MEDLINE Link].
Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis?. Crit Care Med. 1999 Dec. 27(12):2690-3. [QxMD MEDLINE Link].
Wagner A, Risse A, Brill HL, et al. Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application. Diabetes Care. 1999 May. 22(5):674-7. [QxMD MEDLINE Link].
Warner EA, Greene GS, Buchsbaum MS, Cooper DS, Robinson BE. Diabetic ketoacidosis associated with cocaine use. Arch Intern Med. 1998 Sep 14. 158(16):1799-802. [QxMD MEDLINE Link].
Whiteman VE, Homko CJ, Reece EA. Management of hypoglycemia and diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 1996 Mar. 23(1):87-107. [QxMD MEDLINE Link].
Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006 May. 29(5):1150-9. [QxMD MEDLINE Link].
Yan SH, Sheu WH, Song YM, Tseng LN. The occurrence of diabetic ketoacidosis in adults. Intern Med. 2000 Jan. 39(1):10-4. [QxMD MEDLINE Link].
Younis N, Austin MJ, Casson IF. A respiratory complication of diabetic ketoacidosis. Postgrad Med J. 1999 Dec. 75(890):753-4. [QxMD MEDLINE Link].

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Author

Osama Hamdy, MD, PhD Medical Director, Obesity Clinical Program, Director of Inpatient Diabetes Program, Joslin Diabetes Center; Associate Professor of Medicine, Harvard Medical School

Osama Hamdy, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: on advisory panel of Astra-Zeneca Inc<br/>Received research grant from: USDA Dairy Council <br/>Have a 5% or greater equity interest in: HealthyMation Inc<br/>Received consulting fee from Merck Inc for teaching; Received consulting fee from Abbott Nutrition for consulting; for: Receieved consulting fee Sanofi Aventis for teaching.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians