Diabetic ketoacidosis overview

# Overview
Diabetic ketoacidosis (DKA) is a life-threatening complication in patients with untreated diabetes mellitus (chronic high blood sugar or hyperglycemia). Near-complete deficiency of insulin and elevated levels of certain stress hormones combine to cause DKA. DKA is more common among type I diabetics, but may also occur in type II diabetics generally when physiologically stressed, such as during an infection.  Patients with new, undiagnosed Type I diabetes frequently present to hospitals with DKA. DKA can also occur in a known diabetic who fails to take prescribed insulin. DKA was a major cause of death in type I diabetics before insulin injections were available; untreated DKA has a high mortality rate. DKA may be classified according to severity into mild, moderate, and severe DKA. The classification system takes into account various parameters such as arterial pH, anion gap, effective serum osmolarity, mental status, serum bicarbonate levels, and serum ketone levels. The classification of DKA has important implications for the management of the disease. DKA must be differentiated from other conditions presenting with hyperglycemia, ketosis, and metabolic acidosis. The differentials include diabetes mellitus, non-ketotic hyperosmolar state, impaired glucose tolerance, ketotic hypoglycemia, alcoholic ketosis, starvation ketosis, lactic acidosis, salicylic acid ingestion, uremic acidosis, and drug-induced acidosis. These conditions may be differentiated on the basis of the patient's history, clinical features, and laboratory abnormalities. In the Unites States, the number of hospital discharges with DKA as the first-listed diagnosis increased from about 80,000 discharges in 1988 to about 140,000 in 2009. The case-fatality rate of DKA varies according to the geographic region and ranges from a low of less than 1000 per 100,000 individuals (USA and Scotland) to a high of 30,000 per 100,000 individuals (India). If left untreated, patients with diabetic ketoacidosis (DKA) may progress to develop multi-organ failure and death. Common complications of diabetic ketoacidosis (DKA) include hypokalemia, cerebral edema, hyperglycemia, ketoacidemia, renal tubular necrosis, and pulmonary edema. The most common symptoms of DKA include extreme tiredness, vomiting, abdominal pain, fruity-smelling breath, weight loss, and polyuria. The mainstay of therapy for DKA is medical therapy including intravenous insulin, fluids, potassium replacement, and bicarbonate therapy in case of severe acidosis (pH <6.9). The basic principles guiding therapy include rapid restoration of adequate circulation and perfusion, insulin to reverse ketosis and lower glucose levels, and close monitoring to prevent and treat complications if they develop. There are minor differences in the management of DKA in U.S.A. and U.K.; these are opinion-based and depend on the healthcare setting.

# Historical Perspective
Diabetic ketoacidosis (DKA) was described for the first time by Dreschfeld in 1886 and identified as one of the sudden causes of death in diabetes mellitus. In 1971, it was found that the pathogenesis of DKA involved a deficiency of insulin and an excess of glucagon. In the 20th century, major advances were made in the field of management of DKA, starting from the isolation and use of insulin in patients to the adjustment of doses of insulin to achieve optimum control of the disease.

# Classification
Diabetic ketoacidosis (DKA) may be classified according to severity into mild, moderate and severe DKA. The classification takes into account various parameters for example, arterial pH, anion gap, effective serum osmolarity, mental status, serum bicarbonate levels and serum ketone levels. Classification of DKA has important implications in the management of the disease.

# Pathophysiology
Development of diabetic ketoacidosis (DKA) is the result of a relative or absolute deficiency of insulin and an excess of glucagon. In diabetic patients, this leads to a shift from an anabolic state to a catabolic state. This leads to activation of various enzymes that cause an increase in blood glucose levels (via glycogenolysis and gluconeogenesis) and blood ketone levels (via lipolysis). The severe hyperglycemia results in glucosuria and osmotic diuresis leading to a state of dehydration. Muscle wasting is a consequence of proteolysis due an excess of counter-regulatory hormones (glucagon, catecholamines and cortisol).

# Causes
Diabetic ketoacidosis (DKA) can be caused by a deficiency of insulin and an excess of glucagon. This process may be triggered by presence of any infection, lack of adherence to insulin treatment by diabetics, illness, prescription or illicit drugs and any condition that puts the body under physiological stress.

# Differentiating Diabetic Ketoacidosis from other Diseases
Diabetic ketoacidosis (DKA) must be differentiated from other conditions presenting with hyperglycemia, ketosis and metabolic acidosis. The differentials include diabetes mellitus, non-ketotic hyperosmolar state, impaired glucose tolerance, ketotic hypoglycemia, alcoholic ketosis, starvation ketosis, lactic acidosis, salicylic acid ingestion, uremic acidosis and drug-induced acidosis. All these conditions may be differentiated on the basis of history findings, clinical features and laboratory abnormalities.

# Epidemiology and Demographics
In 2007, the incidence of diabetic ketoacidosis (DKA) was estimated to be 13 to 26 cases per 100,000 individuals worldwide. In the Unites States, the number of hospital discharges with DKA as the first-listed diagnosis increased from about 80,000 discharges in 1988 to about 140,000 in 2009. Case-fatality rate of DKA varies according to the geographic region and ranges from a low of less than 1000 per 100,000 individuals (USA and Scotland) to a high of 30,000 per 100,000 individuals (India). The prevalence of DKA varies with age and is more common in children.

# Risk Factors
Common risk factors in the development of diabetic ketoacidosis (DKA) are young age, high mean glycosylated hemoglobin A1c, infection, low physical activity, depression, lack of health insurance, low socioeconomic status, low body mass index, improper management of diabetes, and unemployment.

# Screening
There is insufficient evidence to recommend routine screening for diabetic ketoacidosis (DKA) but urine ketone dip test may be used in high-risk populations.

# Natural History, Complications and Prognosis
If left untreated, patients with diabetic ketoacidosis (DKA) may progress to develop multi-organ failure and death. Common complications of diabetic ketoacidosis (DKA) include hypokalemia, cerebral edema, hyperglycemia, ketoacidemia, renal tubular necrosis, and pulmonary edema.

# Diagnosis

## Diagnostic Criteria
There are specific cut-offs for serum glucose level, ketone levels, body pH and serum bicarbonate levels for the diagnosis for diabetic ketoacidosis as outlined by the American Association of Clinical Endocrinologists.

## History and Symptoms
A positive history of type 1 diabetes mellitus, infection and history of poor compliance to insulin regimens are suggestive of diabetic ketoacidosis (DKA). The most common symptoms of DKA include extreme tiredness, vomiting, abdominal pain, fruity smell of breath, weight loss and polyuria.

## Physical Examination
Patients with diabetic ketoacidosis (DKA) may usually appear cachexic, diaphoretic or obtunded. Physical examination of patients with DKA is usually remarkable for hypothermia, hypotension, tachycardia, tachypnea, kussmaul breathing pattern, acanthosis nigricans, nausea, vomiting and abdominal pain.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of diabetic ketoacidosis (DKA) include blood pH  10 mEq/L and increased serum osmolarity.

## Electrocardiogram
Patients suffering from diabetic ketoacidosis (DKA) may exhibit electrocardiographic (EKG) changes characteristic of toxic hyperkalemia and hypocalcemia. Common abnormalities observed on EKG include tall peaking T waves, prolonged QT interval and widening of QRS complex.

## Chest X Ray
There are no chest x-ray abnormalities associated with diabetic ketoacidosis (DKA).

## CT
Diabetic ketoacidosis (DKA) is associated with cerebral edema which can be visualized on CT scan of the head.

## MRI
MRI in cerebral edema due to diabetic ketoacidosis (DKA) may show hyperattenuating signal on T2 FLAIR MRI.

## Echocardiography or Ultrasound
There are no ultrasound findings associated with diabetic ketoacidosis (DKA).

## Other Imaging Findings
There are no other imaging findings associated with diabetic ketoacidosis (DKA).

## Other Diagnostic Studies
There are no other diagnostic studies associated with diabetic ketoacidosis (DKA).

# Treatment

## Medical Therapy
Diabetic ketoacidosis (DKA) is a medical emergency. The mainstay of therapy for DKA is medical therapy including intravenous insulin, fluids, potassium replacement, and bicarbonate therapy in case of severe acidosis (pH <6.9). The basic principles guiding therapy include rapid restoration of adequate circulation and perfusion, insulin to reverse ketosis and lower glucose levels, and close monitoring to prevent and treat complications if they develop. There are minor differences in the management of DKA in U.S.A. and U.K.; these are opinion-based and depend on the healthcare setting.

## Surgery
Surgical intervention is not recommended for the management of diabetic ketoacidosis (DKA).

## Primary Prevention
Effective measures for the primary prevention of diabetic ketoacidosis (DKA) include recognition of early signs of DKA, implementation of early and aggressive interventions (especially in patients with recurrent episodes of DKA), and administration of optimum anti-diabetic medications in diabetic patients.

## Secondary Prevention
Secondary prevention of diabetic ketoacidosis (DKA) is similar to primary prevention.