eMedicine Specialties > Endocrinology > Diabetes Mellitus

Diabetic Ketoacidosis

Author: Osama Hamdy, MD, PhD, Instructor, Department of Internal Medicine, Joslin Diabetes Center, Harvard Medical School
Contributor Information and Disclosures

Updated: Jul 14, 2008

Introduction

Background

Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes. DKA mainly occurs in patients with type 1 diabetes, but it is not uncommon in some patients with type 2 diabetes. DKA is defined clinically as an acute state of severe uncontrolled diabetes that requires emergency treatment with insulin and intravenous fluids. Biochemically, DKA is defined as an increase in the serum concentration of ketones greater than 5 mEq/L, a blood glucose level of greater than 250 mg/dL (although it is usually much higher), blood pH of less than 7.2, and a bicarbonate level of 18 mEq/L or less.

Pathophysiology

DKA is a complex disordered metabolic state characterized by hyperglycemia, acidosis, and ketonuria. DKA usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter-regulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine). This type of hormonal imbalance enhances hepatic gluconeogenesis, glycogenolysis, and lipolysis.

Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency, and counter-regulatory hormone excess result in severe hyperglycemia, while lipolysis increases serum free fatty acids. Hepatic metabolism of free fatty acids as an alternative energy source (ie, ketogenesis) results in accumulation of acidic intermediate and end metabolites (ie, ketones, ketoacids). Ketones include acetone, beta hydroxybutyrate, and acetoacetate.

Progressive rise of blood concentration of these acidic organic substances initially leads to a state of ketonemia. Natural body buffers can buffer ketonemia in its early stages. When the accumulated ketones exceed the body's capacity of extracting them, they overflow into urine (ie, ketonuria). If the situation is not treated promptly, more accumulation of organic acids leads to frank clinical metabolic acidosis (ie, ketoacidosis), with a drop in pH and bicarbonate serum levels. Respiratory compensation of this acidotic condition results in rapid shallow breathing (Kussmaul respirations).

Ketones, in particular beta hydroxybutyrate, induce nausea and vomiting that consequently aggravate fluid and electrolyte loss already existing in DKA. Moreover, acetone produces the characteristic fruity breath odor of ketotic patients.

Hyperglycemia usually exceeds the renal threshold of glucose absorption and results in significant glycosuria. Consequently, water loss in the urine is increased due to osmotic diuresis induced by glycosuria. This incidence of increased water loss results in severe dehydration, thirst, tissue hypoperfusion, and, possibly, lactic acidosis.

Typical free water loss in DKA is approximately 6 liters or nearly 100 mL/kg of body weight. The initial half of this amount is derived from intracellular fluid and precedes signs of dehydration, while the other half is from extracellular fluid and is responsible for signs of dehydration.

Hyperglycemia, osmotic diuresis, serum hyperosmolarity, and metabolic acidosis result in severe electrolyte disturbances. The most characteristic disturbance is total body potassium loss. This loss is not mirrored in serum potassium levels, which may be low, within the reference range, or even high. Potassium loss is caused by a shift of potassium from the intracellular to the extracellular space in an exchange with hydrogen ions that accumulate extracellularly in acidosis. A large part of the shifted extracellular potassium is lost in urine because of osmotic diuresis. Patients with initial hypokalemia are considered to have severe and serious total body potassium depletion. High serum osmolarity also drives water from intracellular to extracellular space, causing dilutional hyponatremia. Sodium also is lost in the urine during the osmotic diuresis.

Typical overall electrolyte loss includes 200-500 mEq/L of potassium, 300-700 mEq/L of sodium, and 350-500 mEq/L of chloride. The combined effects of serum hyperosmolarity, dehydration, and acidosis result in increased osmolarity in brain cells that clinically manifests as an alteration in the level of consciousness.

Frequency

United States

Currently, DKA occurs less frequently in patients with known diabetes because of the introduction of diabetes educational programs in most diabetes clinics. These programs teach patients with diabetes how to test for urinary ketones and how to adjust their insulin regimen on sick days in order to avoid DKA.

In spite of the advancement in self-care of patients with diabetes, DKA still accounts for 50% of diabetes-related admissions in young persons and 1-2% of all primary diabetes-related admissions. DKA frequently is observed during the diagnosis of type 1 diabetes and frequently indicates this diagnosis. Exact incidence is not known, but it is estimated to be 1 out of 2000.

Although DKA was a common problem in patients with diabetes who were treated with continuous subcutaneous insulin infusion (SCII) through insulin infusion pumps, incidence of DKA became less frequent with the introduction of new pumps equipped with sensitive electronic alarm systems that alert users when the infusion catheter is blocked. Frequent blood glucose monitoring at home makes DKA less likely to occur in such patients because they always can search, in a timely manner, for possible reasons for unexpectedly high blood glucose values before the condition progresses to DKA.

DKA also occurs in pregnant women, either with preexisting diabetes or with diabetes diagnosed during pregnancy. Physiologic changes unique to pregnancy provide a background for the development of DKA. DKA in pregnancy is a medical emergency, as both the mother and the fetus are at risk for significant morbidity and mortality.

International

Incidence is not known but may be higher in developing countries.

Mortality/Morbidity

When DKA is treated properly, it rarely causes any residual effects. The overall mortality rate from DKA ranges from 1-10% of all DKA admissions, according to hospital facilities and the experiences of people who have dealt with this acute metabolic condition. Better understanding of the pathophysiology of DKA and proper monitoring and correction of electrolytes has resulted in significant reduction in the overall mortality rate from this life-threatening condition in most developed countries. Mortality rates from DKA have markedly decreased from 7.96% 20 years ago to 0.67%.¹

• Best results are always observed in patients treated in ICUs during the first 1-2 days of hospitalization.
• In contrast, the mortality rate still is high in developing countries and among nonhospitalized patients. This high mortality rate illustrates the necessity of early diagnosis and the implementation of effective prevention programs.
• Cerebral edema remains the most common cause of mortality, particularly in young children and adolescents.² Cerebral edema frequently results from rapid intracellular fluid shifts. Other causes of mortality include severe hypokalemia, adult respiratory distress syndrome, and comorbid states (eg, pneumonia, acute myocardial infarction).

Race

Incidence of DKA is higher in whites because of the higher incidence of type 1 diabetes in this racial group.

Sex

Incidence of DKA is slightly more common in females than in males for reasons that are unclear. Recurrent DKA is frequently seen in young women with type 1 diabetes mellitus (DM) and is mostly caused by the omission of insulin treatment.

Age

DKA is much more common in young children and adolescents than it is in adults with type 1 diabetes.

Clinical

History

• Insidious increased thirst (ie, polydipsia) and urination (ie, polyuria) are the most common early symptoms of diabetic ketoacidosis (DKA).
• Nausea and vomiting usually occur and may be associated with diffuse abdominal pain.
• Generalized weakness and fatigability may occur.
• Altered consciousness in the form of mild disorientation or confusion is a possible symptom. Although frank coma is uncommon, it may occasionally occur when the condition is neglected or if dehydration or acidosis is severe.
• Symptoms of possible associated intercurrent infection may include fever, dysuria, coughing, malaise, and arthralgia, among others.
• 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.
• Patients may present with a history of failure to comply with insulin therapy or missed insulin injections due to vomiting or psychological reasons.
• History of rapid weight loss is a symptom in patients who are newly diagnosed with type 1 diabetes.

Physical

• Signs of dehydration - Weak and rapid pulse, dry tongue and skin, hypotension, and increased capillary refill time
• Patient odor - Characteristic acetone odor
• Signs of acidosis - Shallow rapid breathing or air hunger (Kussmaul or sighing respiration), abdominal tenderness, and disturbance of consciousness
  • Although these signs are not usual in all cases of DKA, their presence signifies a severe form of DKA.
  • Emphasizing that no direct correlation exists between the degree of acidosis, hyperglycemia, and the disturbances in the level of consciousness is important.
• Signs of intercurrent illness - Myocardial infarction, urinary tract infection (UTI), pneumonia, and perinephric abscess, among others
  • Noticing that the body temperature may be within the reference range or low, even in the presence of intercurrent infection, is particularly important.
  • Search for signs of infection is mandatory in all cases.

Causes

• Patients with type 1 diabetes³
  • DKA present at diagnosis of type 1 diabetes due to acute insulin deficiency (occurs in 25% of patients)
  • Poor compliance with insulin through the omission of insulin injections either due to lack of patient or guardian education or as a result of psychological stress, particularly in adolescents
  • Bacterial infection and intercurrent illness (eg, UTI, vomiting)
  • Klebsiella pneumoniae (the leading cause of bacterial infections precipitating DKA)
  • Medical, surgical, or emotional stress
  • Brittle diabetes
  • Idiopathic (no identifiable cause)
  • Insulin infusion catheter blockage
  • Mechanical failure of insulin infusion pump
• Patients with type 2 diabetes
  • Intercurrent illness (eg, myocardial infarction, pneumonia, prostatitis, UTI)
  • Medication (eg, corticosteroids, pentamidine, clozapine)

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