Diabetic ketoacidosis
Encyclopedia
Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus
. It happens predominantly in those with type 1 diabetes
, but it can occur in those with type 2 diabetes
under certain circumstances. DKA results from a shortage of insulin
; in response the body switches to burning fatty acid
s and producing acidic ketone bodies
that cause most of the symptoms and complications.
DKA may be the first symptom of previously undiagnosed diabetes, but it may also occur in known diabetics due to a variety of causes, such as intercurrent illness or poor compliance with insulin therapy
. Vomiting
, dehydration
, deep gasping breathing
, confusion
and occasionally coma
are typical symptoms. DKA is diagnosed with blood
and urine tests
; it is distinguished from other, rarer forms of ketoacidosis
by the presence of high blood sugar
levels. Treatment involves intravenous fluids to correct dehydration, insulin to suppress the production of ketone bodies, treatment for any underlying causes such as infections, and close observation to prevent and identify complications.
DKA is a medical emergency
, and without treatment it can lead to death. DKA was first described in 1886; until the introduction of insulin therapy in the 1920s it was almost universally fatal. It now carries a mortality of less than 5% with adequate and timely treatment.
and vomiting, pronounced thirst, excessive urine production
and abdominal pain
that may be severe. Those who measure their glucose levels themselves may notice hyperglycemia
(high blood sugar levels). In severe DKA, breathing becomes labored and of a deep, gasping character (a state referred to as "Kussmaul respiration"). The abdomen may be tender to the point that an acute abdomen
may be suspected, such as acute pancreatitis
, appendicitis
or gastrointestinal perforation
. Coffee ground vomiting
(vomiting of altered blood) occurs in a minority of patients; this tends to originate from erosion of the esophagus
. In severe DKA, there may be confusion, lethargy, stupor or even coma (a marked decrease in the level of consciousness).
On physical examination
there is usually clinical evidence of dehydration, such as a dry mouth and decreased skin turgor. If the dehydration is profound enough to cause a decrease in the circulating blood volume, tachycardia
(a fast heart rate) and low blood pressure
may be observed. Often, a "ketotic" odor is present, which is often described as "fruity", often compared to the smell of pear drops whose scent is a ketone. If Kussmaul respiration is present, this is reflected in an increased respiratory rate
.
Small children with DKA are relatively prone to cerebral edema
(swelling of the brain tissue), which may cause headache, coma, loss of the pupillary light reflex, and progress to death. It occurs in 0.7–1.0% of children with DKA, and has been described in young adults, but is overall very rare in adults. It carries a 20–50% mortality.
, influenza
, gastroenteritis
, a urinary tract infection
), pregnancy
, inadequate insulin administration (e.g. defective insulin pen device), myocardial infarction
(heart attack), stroke
or the use of cocaine
. Young patients with recurrent episodes of DKA may have an underlying eating disorder
, or may be using insufficient insulin for fear that it will cause weight gain
. In 5% of cases, no cause for the DKA episode is found.
Diabetic ketoacidosis may occur in those previously known to have diabetes mellitus type 2 or in those who on further investigations turn out to have features of type 2 diabetes (e.g. obesity
, strong family history
); this is more common in African, African-American and Hispanic people. Their condition is then labeled "ketosis-prone type 2 diabetes".
(a process that is normally suppressed by insulin) from glycogen
and through gluconeogenesis
. High glucose levels spill over into the urine, taking water and solutes (such as sodium
and potassium
) along with it in a process known as osmotic diuresis
. Ketones, too, participate in osmotic diuresis and lead to further electrolyte
losses. This leads to polyuria, dehydration, and compensatory thirst and polydipsia. The absence of insulin also leads to the release of free fatty acid
s from adipose tissue
, which are converted, again in the liver, into ketone bodies (acetoacetate and β-hydroxybutyrate). β-Hydroxybutyrate can serve as an energy source in absence of insulin-mediated glucose delivery, and is a protective mechanism in case of starvation. The ketone bodies, however, have a low pH
and therefore turn the blood acidic (metabolic acidosis
). The body initially buffers
the change with the bicarbonate buffering system
, but this system is quickly overwhelmed and other mechanisms must work to compensate for the acidosis. One such mechanism is hyperventilation
to lower the blood carbon dioxide
levels (a form of compensatory respiratory alkalosis
). This hyperventilation, in its extreme form, may be observed as Kussmaul respiration.
In various situations such as infection, insulin demands rise but are not matched by the failing pancreas. Blood sugars rise, dehydration ensues, and resistance to the normal effects of insulin
increases further by way of a vicious circle
.
As a result of the above mechanisms, the average adult DKA patient has a total body water shortage of about 6 liters (or 100 mL/kg), in addition to substantial shortages in sodium, potassium
, chloride
, phosphate
, magnesium
and calcium
. Glucose levels usually exceed 13.8 mmol/L or 250 mg/dL
DKA is common in type 1 diabetes as this form of diabetes is associated with an absolute lack of insulin production by the islets of Langerhans
. In type 2 diabetes, insulin production is present but is insufficient to meet the body's requirements as a result of end-organ insulin resistance. Usually, these amounts of insulin are sufficient to suppress ketogenesis. If DKA occurs in type 2 diabetics, their condition is called "ketosis-prone type 2 diabetes". The exact mechanism for this phenomenon is unclear, but it appears that very high levels of glucose suppress the release of insulin from the pancreas through "glucotoxicity", leading to levels that are insufficient to suppress ketogenesis. Furthermore, insulin resistance may be so severe that ketogenesis cannot be suppressed. Once the condition has been treated, insulin production resumes and often the patient may be able to resume diet or tablet treatment like other type 2 diabetics. Nevertheless, a small proportion of this population has detectable antibodies
against islets of Langerhans, and could therefore be regarded as having a form of type 1 diabetes.
The clinical state of DKA is associated, in addition to the above, with the release of various counterregulatory hormone
s such as glucagon
and adrenaline as well as cytokine
s, the latter of which leads to increased markers of inflammation
, even in the absence of infection
.
Cerebral edema, which is the most dangerous DKA complication, is probably the result of a number of factors. Some authorities maintain that it is the result from overvigorous fluid replacement, but the complication may develop before treatment has been commenced. It is more likely in those with more severe DKA, and in the first episode of DKA. Likely factors in the development of cerebral edema are dehydration, acidosis and low carbon dioxide levels; in addition, the increased level of inflammation and coagulation
may, together with these factors, lead to decreased blood flow to parts of the brain, which then swells up once fluid replacement has been commenced. The swelling of brain tissue leads to raised intracranial pressure
ultimately leading to death.
(high blood sugars), ketones in the blood or on urinalysis
and acidosis are demonstrated. Arterial blood gas
measurement is usually performed to demonstrate the acidosis; this requires taking a blood sample from an artery
. Subsequent measurements (to ensure treatment is effective), may be taken from a normal blood test taken from a vein
, as there is little difference between the arterial and the venous pH.
In addition to the above, blood samples are usually taken to measure urea
and creatinine
(measures of kidney function
, which may be impaired in DKA as a result of dehydration) and electrolytes. Furthermore, markers of infection (complete blood count
, C-reactive protein
) and acute pancreatitis
(amylase
and lipase
) may be measured. Given the need to exclude infection, chest radiography
and urinalysis are usually performed.
If cerebral edema is suspected because of confusion, recurrent vomiting or other symptoms, computed tomography
may be performed to assess its severity and to exclude other causes such as stroke
.
(HHS, sometimes labeled "hyperosmolar non-ketotic state" or HONK) is much more common in type 2 diabetes and features increased plasma osmolarity (above 320 mosm/kg) due to profound dehydration and concentration of the blood; mild acidosis and ketonemia may occur in this state, but not to the extent observed in DKA. There is a degree of overlap between DKA and HHS, as in DKA the osmolarity may also be increased, but in most situations it is possible to classify a case into either DKA or HHS.
Ketoacidosis
is not always the result of diabetes. It may also result from alcohol excess
and from starvation
; in both states the glucose level is normal or low. Metabolic acidosis
may occur in diabetics for other reasons, such as poison
ing with ethylene glycol
or paraldehyde
. Type 2 diabetics taking metformin
may develop lactic acidosis
as a rare side-effect of their medication.
A 2006 American Diabetes Association
statement (for adults) categorizes DKA into one of three stages of severity:
A 2004 statement by the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (for children) uses slightly different cutoffs, where mild DKA is defined by pH 7.20–7.30 (bicarbonate 10–15 mmol/l), moderate DKA by pH 7.1–7.2 (bicarbonate 5–10) and severe DKA by pH<7.1 (bicarbonate below 5).
or similar high-dependency area or ward for close observation may be necessary.
with insufficient blood supply to the body's organs), or a depressed level of consciousness, rapid infusion of saline
(1 liter for adults, 10 ml/kg in repeated doses for children) is recommended to restore circulating volume. Slower rehydration based on calculated water and sodium shortage may be possible if the dehydration is moderate, and again saline is the recommended fluid. Very mild ketoacidosis with no associated vomiting and mild dehydration may be treated with oral rehydration and subcutaneous rather than intravenous insulin under observation for signs of deterioration.
A special but unusual consideration is cardiogenic shock
, where the blood pressure is decreased not due to dehydration but due to inability of the heart to pump blood through the blood vessels. This situation requires ICU admission, monitoring of the central venous pressure
(which requires the insertion of a central venous catheter
in a large upper body vein), and the administration of medication that increases the heart pumping action
and blood pressure.
In general, insulin is given at 0.1 unit/kg per hour to reduce the blood sugars and suppress ketone production. Guidelines differ as to which dose to use when blood sugar levels start falling; some recommend reducing the dose of insulin once glucose falls below 16.6 mmol/l (300 mg/dl) but other recommend infusing glucose in addition to saline to allow for ongoing infusion of higher doses of insulin.
. A large part of the shifted extracellular potassium would have been lost in urine because of osmotic diuresis. Hypokalemia
(low blood potassium concentration) often follows treatment. This increases the risk of dangerous irregularities in the heart rate. Therefore, continuous observation of the heart rate is recommended, as well as repeated measurement of the potassium levels and addition of potassium to the intravenous fluids once levels fall below 5.3 mmol/l. If potassium levels fall below 3.3 mmol/l, insulin administration may need to be interrupted to allow correction of the hypokalemia.
solution to rapidly improve the acid levels in the blood is controversial. There is little evidence that it improves outcomes beyond standard therapy, and indeed some evidence that while it may improve the acidity of the blood, it may actually worsen acidity inside the body's cells and increase the risk of certain complications. Its use is therefore discouraged, although some guidelines recommend it for extreme acidosis (pH<6.9), and smaller amounts for severe acidosis (pH 6.9–7.0).
and hypertonic saline (3%) are used—as in some other forms of cerebral edema—in an attempt to reduce the swelling.
In patients with suspected ketosis-prone type 2 diabetes, determination of antibodies against glutamic acid decarboxylase and islet cells
may aid in the decision whether to continue insulin administration long-term (if antibodies are detected), or whether to attempt treatment with oral medication as in type 2 diabetes.
, a German pathologist working in Manchester
, United Kingdom. In his description, which he gave in an 1886 lecture at the Royal College of Physicians
in London, he drew on reports by Adolph Kussmaul
as well as describing the main ketones, acetoacetate and β-hydroxybutyrate, and their chemical determination. The condition remained almost universally fatal until the discovery of insulin in the 1920s; by the 1930s, mortality had fallen to 29%, and by the 1950s it had become less than 10%. The entity of cerebral edema due to DKA was described in 1936 by a team of doctors from Philadelphia.
Numerous research studies since the 1950s have focused on the ideal treatment for diabetic ketoacidosis. A significant proportion of these studies have been conducted at the University of Tennessee Health Science Center
and Emory University School of Medicine
. Treatment options studied have included high- or low-dose intravenous, subcutaneous or intramuscular (e.g. the "Alberti
regime") insulin, phosphate supplementation, need for a loading dose of insulin, and appropriateness of using bicarbonate therapy in moderate DKA. Various questions remain unanswered, such as whether bicarbonate administration in severe DKA makes any real difference to the clinical course, and whether an insulin loading dose is needed in adults.
The entity of ketosis-prone type 2 diabetes was first fully described in 1987 after several preceding case reports. It was initially thought to be a form of maturity onset diabetes of the young
, and went through several other descriptive names (such as "idiopathic type 1 diabetes", "Flatbush diabetes", "atypical diabetes" and "type 1.5 diabetes") before the current terminology of "ketosis-prone type 2 diabetes" was adopted.
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. It happens predominantly in those with type 1 diabetes
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
, but it can occur in those with type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
under certain circumstances. DKA results from a shortage of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
; in response the body switches to burning fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s and producing acidic ketone bodies
Ketone bodies
Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...
that cause most of the symptoms and complications.
DKA may be the first symptom of previously undiagnosed diabetes, but it may also occur in known diabetics due to a variety of causes, such as intercurrent illness or poor compliance with insulin therapy
Insulin therapy
Insulin therapy is the treatment of diabetes by administration of exogenous insulin.Insulin is used medically to treat some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on external insulin for their survival because the hormone is no longer produced internally...
. Vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, deep gasping breathing
Kussmaul breathing
Kussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis but also renal failure. It is a form of hyperventilation, which is any breathing pattern that reduces carbon dioxide in the blood due to increased rate or...
, confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
and occasionally coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
are typical symptoms. DKA is diagnosed with blood
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
and urine tests
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
; it is distinguished from other, rarer forms of ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....
by the presence of high blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
levels. Treatment involves intravenous fluids to correct dehydration, insulin to suppress the production of ketone bodies, treatment for any underlying causes such as infections, and close observation to prevent and identify complications.
DKA is a medical emergency
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
, and without treatment it can lead to death. DKA was first described in 1886; until the introduction of insulin therapy in the 1920s it was almost universally fatal. It now carries a mortality of less than 5% with adequate and timely treatment.
Signs and symptoms
The symptoms of an episode of diabetic ketoacidosis usually evolve over the period of about 24 hours. Predominant symptoms are nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting, pronounced thirst, excessive urine production
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
and abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
that may be severe. Those who measure their glucose levels themselves may notice hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
(high blood sugar levels). In severe DKA, breathing becomes labored and of a deep, gasping character (a state referred to as "Kussmaul respiration"). The abdomen may be tender to the point that an acute abdomen
Acute abdomen
The term acute abdomen refers to a sudden, severe abdominal pain of unclear etiology that is less than 24 hours in duration. It is in many cases a medical emergency, requiring urgent and specific diagnosis...
may be suspected, such as acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
, appendicitis
Appendicitis
Appendicitis is a condition characterized by inflammation of the appendix. It is classified as a medical emergency and many cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of the risk of rupture leading to...
or gastrointestinal perforation
Gastrointestinal perforation
Gastrointestinal perforation is a complete penetration of the wall of the stomach, small intestine or large bowel, resulting in intestinal contents flowing into the abdominal cavity. Perforation of the intestines results in the potential for bacterial contamination of the abdominal cavity...
. Coffee ground vomiting
Coffee ground vomiting
Coffee ground vomitus refers to a particular appearance of vomit. Blood contains iron within heme molecules in red blood cells. When this iron has been exposed to gastric acid for some time, it becomes oxidized. This reaction causes the vomitus to look like ground coffee. Coffee-ground vomitus is...
(vomiting of altered blood) occurs in a minority of patients; this tends to originate from erosion of the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
. In severe DKA, there may be confusion, lethargy, stupor or even coma (a marked decrease in the level of consciousness).
On physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
there is usually clinical evidence of dehydration, such as a dry mouth and decreased skin turgor. If the dehydration is profound enough to cause a decrease in the circulating blood volume, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
(a fast heart rate) and low blood pressure
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
may be observed. Often, a "ketotic" odor is present, which is often described as "fruity", often compared to the smell of pear drops whose scent is a ketone. If Kussmaul respiration is present, this is reflected in an increased respiratory rate
Respiratory rate
Respiratory rate is also known by respiration rate, pulmonary ventilation rate, ventilation rate, or breathing frequency is the number of breaths taken within a set amount of time, typically 60 seconds....
.
Small children with DKA are relatively prone to cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
(swelling of the brain tissue), which may cause headache, coma, loss of the pupillary light reflex, and progress to death. It occurs in 0.7–1.0% of children with DKA, and has been described in young adults, but is overall very rare in adults. It carries a 20–50% mortality.
Cause
DKA most frequently occurs in those who already have diabetes, but it may also be the first presentation in someone who had not previously been known to be diabetic. There is often a particular underlying problem that has led to the DKA episode; this may be intercurrent illness (pneumoniaPneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...
, a urinary tract infection
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
), pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, inadequate insulin administration (e.g. defective insulin pen device), myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack), stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
or the use of cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
. Young patients with recurrent episodes of DKA may have an underlying eating disorder
Eating disorder
Eating disorders refer to a group of conditions defined by abnormal eating habits that may involve either insufficient or excessive food intake to the detriment of an individual's physical and mental health. Bulimia nervosa, anorexia nervosa, and binge eating disorder are the most common specific...
, or may be using insufficient insulin for fear that it will cause weight gain
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. In 5% of cases, no cause for the DKA episode is found.
Diabetic ketoacidosis may occur in those previously known to have diabetes mellitus type 2 or in those who on further investigations turn out to have features of type 2 diabetes (e.g. obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, strong family history
Family history
Family history is the systematic narrative and research of past events relating to a specific family, or specific families.- Introduction :...
); this is more common in African, African-American and Hispanic people. Their condition is then labeled "ketosis-prone type 2 diabetes".
Mechanism
Diabetic ketoacidosis arises because of a lack of insulin in the body. The lack of insulin and corresponding elevation of glucagon leads to increased release of glucose by the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
(a process that is normally suppressed by insulin) from glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
and through gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
. High glucose levels spill over into the urine, taking water and solutes (such as sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
) along with it in a process known as osmotic diuresis
Osmotic diuresis
Osmotic diuresis is increased urination caused by the presence of certain substances in the small tubes of the kidneys. The excretion occurs when substances such as glucose enter the kidney tubules and cannot be reabsorbed...
. Ketones, too, participate in osmotic diuresis and lead to further electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
losses. This leads to polyuria, dehydration, and compensatory thirst and polydipsia. The absence of insulin also leads to the release of free fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s from adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
, which are converted, again in the liver, into ketone bodies (acetoacetate and β-hydroxybutyrate). β-Hydroxybutyrate can serve as an energy source in absence of insulin-mediated glucose delivery, and is a protective mechanism in case of starvation. The ketone bodies, however, have a low pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
and therefore turn the blood acidic (metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
). The body initially buffers
Buffer solution
A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. It has the property that the pH of the solution changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a...
the change with the bicarbonate buffering system
Bicarbonate buffering system
The bicarbonate buffering system is an important buffer system in the acid-base homeostasis of living things, including humans. As a buffer, it tends to maintain a relatively constant plasma pH and counteract any force that would alter it....
, but this system is quickly overwhelmed and other mechanisms must work to compensate for the acidosis. One such mechanism is hyperventilation
Hyperventilation
Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, causing excessive expulsion of circulating carbon dioxide. It can result from a psychological state such as a panic attack, from a physiological condition such as metabolic acidosis, can be brought about by...
to lower the blood carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
levels (a form of compensatory respiratory alkalosis
Respiratory alkalosis
Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH...
). This hyperventilation, in its extreme form, may be observed as Kussmaul respiration.
In various situations such as infection, insulin demands rise but are not matched by the failing pancreas. Blood sugars rise, dehydration ensues, and resistance to the normal effects of insulin
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
increases further by way of a vicious circle
Virtuous circle and vicious circle
A virtuous circle and a vicious circle are economic terms. They refer to a complex of events that reinforces itself through a feedback loop. A virtuous circle has favorable results, while a vicious circle has detrimental results...
.
As a result of the above mechanisms, the average adult DKA patient has a total body water shortage of about 6 liters (or 100 mL/kg), in addition to substantial shortages in sodium, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
, chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...
, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
, magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
. Glucose levels usually exceed 13.8 mmol/L or 250 mg/dL
DKA is common in type 1 diabetes as this form of diabetes is associated with an absolute lack of insulin production by the islets of Langerhans
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
. In type 2 diabetes, insulin production is present but is insufficient to meet the body's requirements as a result of end-organ insulin resistance. Usually, these amounts of insulin are sufficient to suppress ketogenesis. If DKA occurs in type 2 diabetics, their condition is called "ketosis-prone type 2 diabetes". The exact mechanism for this phenomenon is unclear, but it appears that very high levels of glucose suppress the release of insulin from the pancreas through "glucotoxicity", leading to levels that are insufficient to suppress ketogenesis. Furthermore, insulin resistance may be so severe that ketogenesis cannot be suppressed. Once the condition has been treated, insulin production resumes and often the patient may be able to resume diet or tablet treatment like other type 2 diabetics. Nevertheless, a small proportion of this population has detectable antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against islets of Langerhans, and could therefore be regarded as having a form of type 1 diabetes.
The clinical state of DKA is associated, in addition to the above, with the release of various counterregulatory hormone
Counterregulatory hormone
A counterregulatory hormone is a hormone that opposes the action of another.The action of insulin is counterregulated by glucagon, adrenaline , noradrenaline , cortisol, and growth hormone...
s such as glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
and adrenaline as well as cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s, the latter of which leads to increased markers of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, even in the absence of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
.
Cerebral edema, which is the most dangerous DKA complication, is probably the result of a number of factors. Some authorities maintain that it is the result from overvigorous fluid replacement, but the complication may develop before treatment has been commenced. It is more likely in those with more severe DKA, and in the first episode of DKA. Likely factors in the development of cerebral edema are dehydration, acidosis and low carbon dioxide levels; in addition, the increased level of inflammation and coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
may, together with these factors, lead to decreased blood flow to parts of the brain, which then swells up once fluid replacement has been commenced. The swelling of brain tissue leads to raised intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
ultimately leading to death.
Investigations
Diabetic ketoacidosis may be diagnosed when the combination of hyperglycemiaHyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
(high blood sugars), ketones in the blood or on urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
and acidosis are demonstrated. Arterial blood gas
Arterial blood gas
An arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
measurement is usually performed to demonstrate the acidosis; this requires taking a blood sample from an artery
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
. Subsequent measurements (to ensure treatment is effective), may be taken from a normal blood test taken from a vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
, as there is little difference between the arterial and the venous pH.
In addition to the above, blood samples are usually taken to measure urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
and creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
(measures of kidney function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
, which may be impaired in DKA as a result of dehydration) and electrolytes. Furthermore, markers of infection (complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
, C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
) and acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
(amylase
Amylase
Amylase is an enzyme that catalyses the breakdown of starch into sugars. Amylase is present in human saliva, where it begins the chemical process of digestion. Food that contains much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns...
and lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
) may be measured. Given the need to exclude infection, chest radiography
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
and urinalysis are usually performed.
If cerebral edema is suspected because of confusion, recurrent vomiting or other symptoms, computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
may be performed to assess its severity and to exclude other causes such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
.
Criteria
Diabetic ketoacidosis is distinguished from other diabetic emergencies by the presence of large amounts of ketones in blood and urine, and marked metabolic acidosis. Hyperosmolar hyperglycemic stateNonketotic hyperosmolar coma
Nonketotic hyperosmolar coma is a type of diabetic coma associated with a high mortality seen in diabetes mellitus type 2. The preferred term used by the American Diabetes Association is hyperosmolar nonketotic state . Other commonly used names are hyperosmolar hyperglycemic nonketotic coma or...
(HHS, sometimes labeled "hyperosmolar non-ketotic state" or HONK) is much more common in type 2 diabetes and features increased plasma osmolarity (above 320 mosm/kg) due to profound dehydration and concentration of the blood; mild acidosis and ketonemia may occur in this state, but not to the extent observed in DKA. There is a degree of overlap between DKA and HHS, as in DKA the osmolarity may also be increased, but in most situations it is possible to classify a case into either DKA or HHS.
Ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....
is not always the result of diabetes. It may also result from alcohol excess
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
and from starvation
Starvation
Starvation is a severe deficiency in caloric energy, nutrient and vitamin intake. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death...
; in both states the glucose level is normal or low. Metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
may occur in diabetics for other reasons, such as poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
ing with ethylene glycol
Ethylene glycol
Ethylene glycol is an organic compound widely used as an automotive antifreeze and a precursor to polymers. In its pure form, it is an odorless, colorless, syrupy, sweet-tasting liquid...
or paraldehyde
Paraldehyde
Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane. The corresponding tetramer is metaldehyde. A colourless liquid, it is sparingly soluble in water and highly soluble in alcohol. Paraldehyde slowly oxidizes in air, turning brown and producing...
. Type 2 diabetics taking metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
may develop lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
as a rare side-effect of their medication.
A 2006 American Diabetes Association
American Diabetes Association
The American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...
statement (for adults) categorizes DKA into one of three stages of severity:
- Mild: blood pH mildly decreased to between 7.25 and 7.30 (normal 7.35–7.45); serum bicarbonate decreased to 15–18 mmol/l (normal above 20); the patient is alert
- Moderate: pH 7.00–7.25, bicarbonate 10–15, mild drowsiness may be present
- Severe: pH below 7.00, bicarbonate below 10, stupor or coma may occur
A 2004 statement by the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (for children) uses slightly different cutoffs, where mild DKA is defined by pH 7.20–7.30 (bicarbonate 10–15 mmol/l), moderate DKA by pH 7.1–7.2 (bicarbonate 5–10) and severe DKA by pH<7.1 (bicarbonate below 5).
Prevention
Attacks of DKA can be prevented in known diabetics to an extent by adherence to "sick day rules"; these are clear-cut instructions to patients on how to treat themselves when unwell. Instructions include advice on how much extra insulin to take when sugar levels appear uncontrolled, an easily digestible diet rich in salt and carbohydrates, means to suppress fever and treat infection, and recommendations when to call for medical help (such as a certified diabetes educator).Management
The main aims in the treatment of diabetic ketoacidosis are replacing the lost fluids and electrolytes while suppressing the high blood sugars and ketone production with insulin. Admission to an intensive care unitIntensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
or similar high-dependency area or ward for close observation may be necessary.
Fluid replacement
The amount of fluid depends on the estimated degree of dehydration. If dehydration is so severe as to cause shock (severely decreased blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
with insufficient blood supply to the body's organs), or a depressed level of consciousness, rapid infusion of saline
Saline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
(1 liter for adults, 10 ml/kg in repeated doses for children) is recommended to restore circulating volume. Slower rehydration based on calculated water and sodium shortage may be possible if the dehydration is moderate, and again saline is the recommended fluid. Very mild ketoacidosis with no associated vomiting and mild dehydration may be treated with oral rehydration and subcutaneous rather than intravenous insulin under observation for signs of deterioration.
A special but unusual consideration is cardiogenic shock
Cardiogenic shock
Cardiogenic shock is based upon an inadequate circulation of blood due to primary failure of the ventricles of the heart to function effectively....
, where the blood pressure is decreased not due to dehydration but due to inability of the heart to pump blood through the blood vessels. This situation requires ICU admission, monitoring of the central venous pressure
Central venous pressure
Central venous pressure describes the pressure of blood in the thoracic vena cava, near the right atrium of the heart...
(which requires the insertion of a central venous catheter
Central venous catheter
In medicine, a central venous catheter is a catheter placed into a large vein in the neck , chest or groin...
in a large upper body vein), and the administration of medication that increases the heart pumping action
Inotrope
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions...
and blood pressure.
Insulin
Some guidelines recommend a bolus (initial large dose) of insulin of 0.1 unit of insulin per kilogram of body weight. This can be administered immediately after the potassium level is known to be higher than 3.3 mmol/l; if the level is any lower, administering insulin could lead to a dangerously low potassium level (see below). Other guidelines recommend delaying the initiation of insulin until fluids have been administrered.In general, insulin is given at 0.1 unit/kg per hour to reduce the blood sugars and suppress ketone production. Guidelines differ as to which dose to use when blood sugar levels start falling; some recommend reducing the dose of insulin once glucose falls below 16.6 mmol/l (300 mg/dl) but other recommend infusing glucose in addition to saline to allow for ongoing infusion of higher doses of insulin.
Potassium
Potassium levels can fluctuate severely during the treatment of DKA, because insulin decreases potassium levels in the blood by redistributing it into cellsCell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. A large part of the shifted extracellular potassium would have been lost in urine because of osmotic diuresis. Hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
(low blood potassium concentration) often follows treatment. This increases the risk of dangerous irregularities in the heart rate. Therefore, continuous observation of the heart rate is recommended, as well as repeated measurement of the potassium levels and addition of potassium to the intravenous fluids once levels fall below 5.3 mmol/l. If potassium levels fall below 3.3 mmol/l, insulin administration may need to be interrupted to allow correction of the hypokalemia.
Bicarbonate
The administration of sodium bicarbonateSodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
solution to rapidly improve the acid levels in the blood is controversial. There is little evidence that it improves outcomes beyond standard therapy, and indeed some evidence that while it may improve the acidity of the blood, it may actually worsen acidity inside the body's cells and increase the risk of certain complications. Its use is therefore discouraged, although some guidelines recommend it for extreme acidosis (pH<6.9), and smaller amounts for severe acidosis (pH 6.9–7.0).
Cerebral edema
Cerebral edema, if associated with coma, often necessitates admission to intensive care, artificial ventilation, and close observation. The administration of fluids is slowed. The ideal treatment of cerebral edema in DKA is not established, but intravenous mannitolMannitol
Mannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
and hypertonic saline (3%) are used—as in some other forms of cerebral edema—in an attempt to reduce the swelling.
Resolution
Resolution of DKA is defined as general improvement in the symptoms, such as the ability to tolerate oral nutrition and fluids, normalization of blood acidity (pH>7.3), and absence of ketones in blood (<1 mmol/l) or urine. Once this has been achieved, insulin may be switched to the usual subcutaneously administrered regimen, one hour after which the intravenous administration can be discontinued.In patients with suspected ketosis-prone type 2 diabetes, determination of antibodies against glutamic acid decarboxylase and islet cells
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
may aid in the decision whether to continue insulin administration long-term (if antibodies are detected), or whether to attempt treatment with oral medication as in type 2 diabetes.
Epidemiology
Diabetic ketoacidosis occurs in 4.6–8.0 per 1000 type 1 diabetics annually. In the United States, 100,000 hospital admissions occur annually as a result of DKA, at an estimated cost of $1 billion or a quarter to a half the total cost of caring for type 1 diabetics. Since the 1980s there has been a documented increasing trend to hospital admissions. The risk is increased in those with an ongoing risk factor, such as an eating disorder, and those who cannot afford insulin. About 30% of children with type 1 diabetes receive their diagnosis after an episode of DKA.History
The first full description of diabetic ketoacidosis is attributed to Julius DreschfeldJulius Dreschfeld
Julius Dreschfeld FRCP was a leading British physician and pathologist.Born in Bavaria of Jewish parents, he was educated at Owens College, Manchester, and Manchester Royal School of Medicine....
, a German pathologist working in Manchester
Manchester
Manchester is a city and metropolitan borough in Greater Manchester, England. According to the Office for National Statistics, the 2010 mid-year population estimate for Manchester was 498,800. Manchester lies within one of the UK's largest metropolitan areas, the metropolitan county of Greater...
, United Kingdom. In his description, which he gave in an 1886 lecture at the Royal College of Physicians
Royal College of Physicians
The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...
in London, he drew on reports by Adolph Kussmaul
Adolph Kussmaul
Adolph Kussmaul was a German physician and a leading clinician of his time. He was born as the son and grandson of physicians at Graben near Karlsruhe and studied at Heidelberg. He entered the army after graduation and spent two years as an army surgeon...
as well as describing the main ketones, acetoacetate and β-hydroxybutyrate, and their chemical determination. The condition remained almost universally fatal until the discovery of insulin in the 1920s; by the 1930s, mortality had fallen to 29%, and by the 1950s it had become less than 10%. The entity of cerebral edema due to DKA was described in 1936 by a team of doctors from Philadelphia.
Numerous research studies since the 1950s have focused on the ideal treatment for diabetic ketoacidosis. A significant proportion of these studies have been conducted at the University of Tennessee Health Science Center
University of Tennessee Health Science Center
The University of Tennessee Health Science Center in Memphis includes the Colleges of Allied Health Sciences, Dentistry, Graduate Health Sciences, Medicine, Nursing and Pharmacy. Its pediatric residency program is affiliated with Le Bonheur Children's Medical Center and residents in pediatrics,...
and Emory University School of Medicine
Emory University School of Medicine
Emory University School of Medicine, a component of Emory’s Robert W. Woodruff Health Sciences Center, is ranked among the nation’s institutions for biomedical education and research...
. Treatment options studied have included high- or low-dose intravenous, subcutaneous or intramuscular (e.g. the "Alberti
George Alberti
Sir Kurt George Matthew Mayer Alberti was the British Government's National Clinical Director for Emergency Access...
regime") insulin, phosphate supplementation, need for a loading dose of insulin, and appropriateness of using bicarbonate therapy in moderate DKA. Various questions remain unanswered, such as whether bicarbonate administration in severe DKA makes any real difference to the clinical course, and whether an insulin loading dose is needed in adults.
The entity of ketosis-prone type 2 diabetes was first fully described in 1987 after several preceding case reports. It was initially thought to be a form of maturity onset diabetes of the young
Maturity onset diabetes of the young
Maturity onset diabetes of the young refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene disrupting insulin production...
, and went through several other descriptive names (such as "idiopathic type 1 diabetes", "Flatbush diabetes", "atypical diabetes" and "type 1.5 diabetes") before the current terminology of "ketosis-prone type 2 diabetes" was adopted.