Diabetic ketoacidosis - Diagnosis Approach (2024)

The symptoms of DKA usually develop rapidly over 1 day or less. DKA may be the initial presentation in up to 25% of people with newly diagnosed diabetes. Hyperglycemia is a key diagnostic criterion for DKA; however, a wide range of plasma glucose levels can be present on admission, and approximately 10% of DKA patients present with glucose <250 mg/dL (“euglycemic DKA”).[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com Hyperosmolar hyperglycemic state (HHS) is often discussed as a separate condition. However, DKA and HHS represent two points on the spectrum of metabolic derangements in diabetes. In contrast to DKA, HHS may evolve insidiously over days to weeks. Symptoms of hyperglycemia in both DKA and HHS include polyuria, polydipsia, weakness, and weight loss.

Important factors to consider in the patient's past or current medical history include infection, myocardial infarction, pancreatitis, stroke, acromegaly, hyperthyroidism, and Cushing syndrome, as these may be precipitants or risk factors for DKA. In euglycemic DKA, pregnancy, starvation, concomitant alcohol use, and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have all been implicated in its etiology.[12]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Sep;38(9):1687-93.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542270http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com[39]Joseph F, Anderson L, Goenka N, et al. Starvation-induced true diabetic euglycemic ketoacidosis in severe depression. J Gen Intern Med. 2009 Jan;24(1):129-31.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607495http://www.ncbi.nlm.nih.gov/pubmed/18975036?tool=bestpractice.com

It is essential to take a full medication history, in particular looking for corticosteroids, thiazides, pentamidine, sympathomimetics, second-generation antipsychotic agents, and immune checkpoint inhibitors, as these affect carbohydrate metabolism and may participate in the development of hyperglycemic crises.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[25]Alavi IA, Sharma BK, Pillay VK. Steroid-induced diabetic ketoacidosis. Am J Med Sci. 1971 Jul;262(1):15-23.http://www.ncbi.nlm.nih.gov/pubmed/4327634?tool=bestpractice.com[11]Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the diabetic hyperosmolar state. J Am Geriatr Soc. 1987 Aug;35(8):737-41.http://www.ncbi.nlm.nih.gov/pubmed/3611564?tool=bestpractice.com[27]Newcomer JW. Second generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005 Dec;19 Suppl 1:1-93.http://www.ncbi.nlm.nih.gov/pubmed/15998156?tool=bestpractice.com Cocaine abuse may be an independent risk factor associated with recurrent DKA.[28]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 Jan-Feb;13(1):22-9.http://www.ncbi.nlm.nih.gov/pubmed/17360297?tool=bestpractice.com[10]Vuk A, Baretic M, Osvatic MM, et al. Treatment of diabetic ketoacidosis associated with antipsychotic medication: literature review. J Clin Psychopharmacol. 2017 Oct;37(5):584-9.http://www.ncbi.nlm.nih.gov/pubmed/28816925?tool=bestpractice.com SGLT-2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin), used for glycemic control of type 2 diabetes, have been the subject of an FDA warning about a risk for DKA.[29]US Food and Drug Administration. FDA drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. December 2015 [internet publication].https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about

Physical exam

Physical signs of volume depletion include dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock. DKA patients may exhibit nausea, vomiting, Kussmaul respiration, acetone breath, and, occasionally, abdominal pain. Abdominal pain may correlate with the degree of acidosis in patients with DKA, and it may be confused with an acute abdominal crisis. Mild hypothermia may be observed in some patients, due to peripheral vasodilation. Hyperthermia is not usual, even in the presence of infection.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com Mental status may be altered in DKA, varying from alert in mild DKA to stupor and/or coma in severe DKA. In HHS, mental obtundation and coma are more frequent. Focal neurologic signs (hemianopia and hemiparesis) and seizures may also be features in HHS.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

Initial laboratory evaluation

Plasma glucose

  • Plasma glucose is typically >250 mg/dL with presence of acidosis and ketonemia. However, a wide range of plasma glucose levels can be present on admission, and approximately 10% of DKA patients present with glucose <250 mg/dL (euglycemic DKA).[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

Urinalysis

  • Positive for glucose and ketones. Other potential findings include leukocytes and nitrites in the presence of infection, and myoglobinuria and/or hemoglobinuria in rhabdomyolysis.

Arterial and venous blood gases

  • Arterial blood gas (ABG) shows a metabolic acidosis, which is essential for the diagnosis of DKA. Arterial pH measurement is necessary for diagnosis of DKA, but venous pH is recommended for monitoring treatment, due to the pain and risk of infection in obtaining frequent arterial samples. A venous pH sample is usually 0.03 units lower than arterial pH, and this difference should be considered.

  • The pH varies from 7.00 to 7.30, and the arterial bicarbonate ranges from <10 mEq/L in severe DKA to >15 mEq/L in mild DKA.

Capillary or serum ketones (beta-hydroxybutyrate)

  • There are three main ketones that are produced in DKA that can be measured: acetone, acetoacetate, and beta-hydroxybutyrate (BOHB).

  • In early DKA, the acetoacetate concentration is low, but it is a major substrate for ketone measurement by many laboratories (nitroprusside reaction method). Therefore, serum ketone measurement by usual laboratory techniques has a high specificity, but low sensitivity for the diagnosis of DKA; hence a negative test for serum ketones does not exclude DKA. Acetone is rarely measured due to its volatile nature.[40]Kemperman FA, Weber JA, Gorgels J, et al. The influence of ketoacids on plasma creatinine assays in diabetic ketoacidosis. J Intern Med. 2000 Dec;248(6):511-7.https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2000.00768.xhttp://www.ncbi.nlm.nih.gov/pubmed/11155144?tool=bestpractice.com Conversely, BOHB is an early and abundant ketoacid that can be the first signal of the development of DKA. Point-of-care BOHB testing is widely available and is highly sensitive and specific for the diagnosis of DKA.[41]Dhatariya K. Blood ketones: measurement, interpretation, limitations, and utility in the management of diabetic ketoacidosis. Rev Diabet Stud. 2016 Winter;13(4):217-25.http://www.ncbi.nlm.nih.gov/pubmed/28278308?tool=bestpractice.com

  • During the treatment of DKA, BOHB is converted to acetoacetate, which is detected by the nitroprusside method. Therefore, the increase in acetoacetate during the treatment of DKA may mistakenly indicate a worsening of ketonemia.

  • Another potential source of error in detecting ketone bodies is the patient's medications. Some drugs, such as the ACE inhibitor captopril, contain sulfhydryl groups that can react with the reagent in the nitroprusside test and give a false-positive result. Therefore, clinical judgement and other biochemical tests will be required in patients who are receiving such medications.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

BUN

  • Typically increased due to volume depletion.

Serum electrolytes[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[18]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.https://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com

Anion gap

  • The calculated serum anion gap in mEq/L (serum sodium-[serum chloride+bicarbonate]) gives an estimate of the unmeasured anions in plasma, which in DKA are ketoacids. The anion gap is typically more than 10 to 12 mEq/L in DKA. [ Anion GapOpens in new window ]

  • Normalization of the anion gap reflects correction of the ketoacidosis as these anions are removed from the blood.

Creatine phosphokinase

  • Rhabdomyolysis is common in cocaine users with concurrent DKA, and creatine phosphokinase levels should be assessed in known or suspected cocaine users who present with DKA.[28]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 Jan-Feb;13(1):22-9.http://www.ncbi.nlm.nih.gov/pubmed/17360297?tool=bestpractice.com

  • In rhabdomyolysis, pH and serum osmolality are usually mildly elevated and plasma glucose and ketones are normal. Myoglobinuria and/or hemoglobinuria are detected on urinalysis.

Serum lactate

  • Measured to exclude lactic acidosis. Lactate levels are normal in DKA but elevated in lactic acidosis.

Liver function tests (LFTs)

  • Usually normal, and are used to screen for an underlying hepatic precipitant. Abnormal LFTs indicate underlying liver disease such as fatty liver, or other conditions such as congestive heart failure.

Serum amylase and lipase

  • Amylase is elevated in the majority of patients with DKA, but this may be due to nonpancreatic sources such as parotid glands.

  • Serum lipase is usually normal and may be beneficial in differentiating pancreatitis in patients with elevated amylase level. However, mildly elevated serum lipase level in the absence of pancreatitis has also been reported in patients with DKA.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

Plasma osmolality

  • This is variable in DKA.

CBC with differential

  • Leukocytosis is present in hyperglycemic crises and correlates with blood ketone levels. However, leukocytosis >25,000/microliter may indicate infection and requires further evaluations.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009 Jul;32(7):1335-43.https://care.diabetesjournals.org/content/32/7/1335.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

Additional tests

ECG

  • Used to exclude myocardial infarction (MI) as a precipitant or to look for cardiac effects of electrolyte disturbances (usually of potassium). Evidence of MI includes Q waves or ST segment changes. Evidence of hypokalemia (U waves) or hyperkalemia (tall T waves) may be present.

  • A high index of suspicion for MI should be maintained as diabetic patients often present with atypical symptoms.

Chest x-ray

  • Indicated to exclude pneumonia. In pneumonia, may show typical changes of pneumonia including infiltration, consolidation, effusions, and cavitation.

Blood, urine, or sputum cultures

  • Should be obtained if there are signs of infection such as chills, constitutional upset (e.g., fatigue, confusion, anxiety), or symptoms and signs of specific infections. The most common precipitating infections are pneumonia and urinary tract infections. Patients are usually normothermic or hypothermic due to peripheral vasodilation so fever may not be seen.

Cardiac biomarkers

  • Usually normal, but are elevated if MI is the precipitant. A high index of suspicion should be maintained as diabetic patients often present with atypical symptoms.

Typical deficits in mild DKA

Typical deficits[18]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.https://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com

Mild DKA:

  • Total water (L): 6

  • Water (mL/kg): 100

  • Na+ (mEq/kg): 7 to 10

  • Cl- (mEq/kg): 3 to 5

  • K+ (mEq/kg): 3 to 5

  • PO4 (mmol/kg): 5 to 7

  • Mg++ (mEq/kg): 1 to 2

  • Ca++ (mEq/kg): 1 to 2.

Notes: Deficits based on per kg of body weight.

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Diabetic ketoacidosis - Diagnosis Approach (2024)
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