Diabetic Ketoacidosis

Abbas E. Kitabchi, PhD., MD., FACP, FACE Professor of Medicine & Molecular Sciences and Maston K. Callison Professor in the Division of Endocrinology, Diabetes & Metabolism UT Health Science Center, 920 Madison Ave., 300A, Memphis, TN 38163
Aidar R. Gosmanov, M.D., Ph.D., D.M.Sc. Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, The University of Tennessee Health Science Center, 920 Madison Avenue, Suite 300A, Memphis, TN  38163

Clinical Recognition

Omission of insulin and infection are the two most common precipitants of DKA. Non-compliance may account for up to 44% of DKA presentations; while infection is less frequently observed in DKA patients.

Acute medical illnesses involving the cardiovascular system (myocardial infarction, stroke, acute thrombosis) and gastrointestinal tract (bleeding, pancreatitis), diseases of endocrine axis (acromegaly, Cushing`s syndrome, hyperthyroidism) and impaired thermo-regulation or recent surgical procedures can contribute to the development of DKA by causing dehydration, increase in insulin counter-regulatory hormones, and worsening of peripheral insulin resistance.

Medications such as diuretics, beta-blockers, corticosteroids, second-generation anti-psychotics, and/or anti-convulsants may affect carbohydrate metabolism and volume status and, therefore, could precipitateDKA.

Other factors: psychological problems, eating disorders, insulin pump malfunction, and drug abuse. It is now recognized that new onset T2DM can manifest with DKA. These patients are obese, mostly African Americans or Hispanics and have undiagnosed hyperglycemia, impaired insulin secretion, and insulin action. A recent report suggests that cocaine abuse is an independent risk factor associated with DKA recurrence.


Insulin deficiency, increased insulin counter-regulatory hormones (cortisol, glucagon, growth hormone, and catecholamines)and peripheral insulin resistance lead to hyperglycemia, dehydration, ketosis, and electrolyte imbalance which underlie the pathophysiology of DKA.

Hyperglycemia of DKA evolves through accelerated gluconeogenesis, glycogenolysis, and decreased glucose utilization – all due to absolute insulin deficiency. Due to increased lipolysis and decreased lipogenesis, abundant free fatty acids are converted to ketone bodies: acetoacetate, β-hydroxybutyrate (β-OHB), and acetone. Hyperglycemia-induced osmotic diuresis, if not accompanied by sufficient oral fluid intake, leads to dehydration, hyperosmolarity, electrolyte loss, and subsequent decrease in glomerular filtration. With decline in a renal function, glycosuria diminishes and hyperglycemia/hyperosmolality worsens. With impaired insulin action and hyperosmolality, utilization of potassium by skeletal muscle is markedly diminished leading to intracellular potassium depletion. Also, potassium is lost via osmotic diuresis causing profound total body potassium deficiency. Therefore, DKA patients can present with broad rangeof serum potassium concentrations. Nevertheless, a “normal” plasma potassium concentration may bepresent when potassium stores in the body are severely diminished and the institution of insulin therapy and correction of hyperglycemia will lead to future hypokalemia.

Diagnosis and Differential

Diagnostic criteria for DKA are presented in Table 1.

Clinical presentation. Polyuria, polydipsia, weight loss, vomiting, and abdominal pain usually are present in patients with DKA. Abdominal pain can be closely associated with acidosis and resolves with treatment. Physical examination findings such as hypotension, tachycardia, poor skin turgor, and weakness support the clinical diagnosis of dehydration in DKA. Mental status changes may occur in DKA and are likely related to degree of acidosis. A search for symptoms of precipitating causes such infection, vascular events, or existing drug abuse should be initiated in the emergency room. Patients with hyperglycemic crises can be hypothermic because of peripheral vasodilation and decreased utilization of metabolic substrates.

Differential diagnosis. Hyperglycemic hyperosmolar state is not associated with ketosis. Starvation and alcoholic ketoacidosis are not characterized by hyperglycemia >200 mg/dl and bicarbonate level <18 meq/L. With hypotension and history of metformin use, lactic acidosis (lactic acid level >7 mmol/L) should be suspected. Ingestion of methanol, isopropyl alcohol, and paraldehyde can also alter anion gap and/or osmolality and need to be investigated.

Table 1 Criteria and classification of (DKA)
DKA Mild Moderate Severe
Plasma glucose (mg/dl) >250 mg/dl >250mg/dl 250mg/dl
Arterial pH 7.25-7.30 7.00-7.24 <7.00
Serum bicarbonate (mEq/L) 15-18 10- 15 <10
Urine ketone* + + +
Serum ketone* + + +
Effective Serum Osmolality Variable Variable Variable
Anion Gap*** >10 >12 >12
Mental Status Alert Alert/drowsy Stupor/coma
*Nitroprusside reaction method
** Serum osmolality: 2x[measured Na +(mEq/L)]+ glucose (mg/dl)/18 = mOsm/kg
*** Anion Gap:[ (Na + )–(Cl - + HCO3 - (mEq/L)]
Table 2. Lab Evaluation of Causes of Acidosis
Factor Studied DKA HHS Star-vation Uremic acidosis
pH normal normal Mild↓
Plasma glucose >500 mg/dl normal normal
Glycosuria + + + + 0 0
Total plasma ketones* ↑↑ 0 or ↑ Mild↑ 0
Anion gap Normal Mild↑ Mild ↑
Osmolality >330 mOsm/kg normal Normal/↑
Other BUN>200 mg/dl
Table 2. continued
Factor Studied DKA Lactic acidosis Alcohol ketosis Methanol Ethyleneglycol
pH ↓↑
Plasma glucose normal N ormal/ ↓ Normal
Glycosuria + + 0 0 0
Total plasma ketones* ↑↑ 0 Normal
Anion gap
Osmolality Normal Normal ↑↑
Other lactate >7 mmol/L Serum levels positive
HHS- hyperglycemic hyperosmolar state
BUN –blood urea nitrogen

*Acetest and Ketostix (Bayer; Leverkusen, Germany) measure acetoacetic acid only; thus, misleadingly low values may be obtained because the majority of “ketone bodies” are β-hydroxybutyrate.

Diagnoctic Tests Needed

Initial necessary tests: basic metabolic panel, osmolality, ketones, β-hydroxybutyrate (β-OH), complete blood count with differential, urinalysis and urine ketones by dipstick, and arterial blood gases.

Additional tests include an electrocardiogram, chest X-ray, and various tissue cultures, if indicated, and HbA1c.

Caveats to diagnostic tests. Anion gap acidosisis calculated by subtracting the sum of Cl and HCO3 from measured (not corrected) Na concentration, should be corrected for hypo-albuminemia. Usually a HCO 3 level of 18-20 meq/L rules out metabolic acidosis. Arterial blood gases with pH<7.30 support the diagnosis. β-OHB is early and abundant ketoacidand indicative of ketosis. Acetoacetate but not acetone, a product of ketone bodyformation, are measured by a majority of laboratories but may be negative in the blood in early DKA. Effective serum osmolality can be measured directly or derived from following formula: 2x [measured Na+ (meq/L)] + glucose/18. High measured Na indicates a significant degree of dehydration. A white blood cell count >25,000 should warrant a comprehensive search for infection. Serum creatinine can be falsely elevated because of acetoacetate interference with the colorimetric creatinine assay.


The therapeutic goals of management include optimization of:

  • volume status,
  • hyperglycemia and ketosis/acidosis,
  • electrolyte abnormalities,
  • potential precipitating factors.

Steps to follow in early stages of DKA management (Figure 1):

  1. Start IV fluids after blood sample for biochemistry is sent to laboratory (Fig. 1A);
  2. Potassium level should be >3.3 meq/L before initiation of insulin therapy (supplement potassium intravenously if needed) (Fig. 1C);
  3. Initiate insulin therapy only when steps 1-2 are executed (Fig. 1B).

Resolution of DKA:

  1. Plasma glucose <200-250 mg/dl,
  2. Serum bicarbonate concentration >18 meq/L,
  3. Venous blood pH >7.3, and
  4. Anion gap <10

Fluid therapy: Replace fluid deficit in DKA (~6 L) within 24-36 hours with the goal of 50% volume replacement within first 12 hours.

Insulin Therapy: Transition to SC insulin by giving long-acting insulin 2 hours before the discontinuation of IV insulin.

Bicarbonate therapy: if pH is < 7.0 or bicarbonate level is < 5 meq/L, administer 100 mmol (2 ampules) of bicarbonate in 200 ml of water with 20 meq of potassium chloride over two hours.

Follow Up

Complications And Discharge

Hypoglycemia and hypokalemia are the most frequent complications and can be prevented by timely adjustment of insulin dose and frequent monitoring of potassium levels.

Non-anion gap hyperchloremic acidosis occurs due to urinary loss of ketoanions which are needed for bicarbonate regeneration and preferential re-absorption of chloride in proximal renal tubule secondary to intensive administration of chloride-containing fluids and low plasma bicarbonate. The acidosis usually resolves and should not affect treatment course.

Cerebral edema is reported in young adult patients. This condition is manifested by appearance of headache, lethargy, papillary changes, or seizures. Mortality is up to 70%. Mannitol infusion and mechanical ventilation should be used to treat this condition.

Rhabdomyolysis is another possible complication due to hyper-osmolality and hypo-perfusion.

Pulmonary edema can develop from excessive fluid replacement in patients with CKD or CHF.

Discharge planning should include diabetes education, selection of appropriate insulin regimen that is understood and afforded by the patient, and preparation of set of supplies for the initial insulin administration at home.


None available


Ketoacidosis and Hyperosmolar Coma-Abbas E Kitabchi, PhD, MD, and Laleh Razavi Nematollahi, in http://www.endotext.org, http://www.endotext.org/diabetes/diabetes24/diabetesframe24.htm

Kitabchi AE, Murphy MB, Spencer J, Matteri R, and Karas J . Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes care 31: 2081-2085, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18694978

Kitabchi AE, Umpierrez GE, Fisher JN, Murphy MB, and Stentz FB . Thirty years of personal experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. The Journal of clinical endocrinology and metabolism 93: 1541-1552, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18270259

Kitabchi AE, Umpierrez GE, Miles JM, and Fisher JN . Hyperglycemic crises in adult patients with diabetes. Diabetes care 32: 1335-1343, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19564476