diabetic ketoacidosis diabetic ketoacidosis diabetic ketoacidosis (dka) is a potentially life-threatening complication of diabetes mellitus. signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of consciousness. a person's breath may develop a specific "fruity" smell. onset of symptoms is usually rapid. people without a previous diagnosis of diabetes may develop dka as the first obvious symptom. diabetic ketoacidosisdehydration may be severe in diabetic ketoacidosis, and intravenous fluids are usually needed as part of its treatment.specialtyendocrinologysymptomsvomiting, abdominal pain, deep gasping breathing, increased urination, confusion, a specific smellcomplicationscerebral edemausual onsetrelatively rapidcausesshortage of insulinrisk factorsusually type 1 diabetes, less often other typesdiagnostic methodhigh blood sugar, low blood ph, ketoacidsdifferential diagnosishyperosmolar nonketotic state, alcoholic ketoacidosis, uremia, salicylate toxicitytreatmentintravenous fluids, insulin, potassiumfrequency4–25% of people with type 1 diabetes per year dka happens most often in those with type 1 diabetes but can also occur in those with other types of diabetes under certain circumstances. triggers may include infection, not taking insulin correctly, stroke and certain medications such as steroids. dka results from a shortage of insulin; in response, the body switches to burning fatty acids, which produces acidic ketone bodies. dka is typically diagnosed when testing finds high blood sugar, low blood ph and ketoacids in either the blood or urine. the primary treatment of dka is with intravenous fluids and insulin. depending on the severity, insulin may be given intravenously or by injection under the skin. usually, potassium is also needed to prevent the development of low blood potassium. throughout treatment, blood sugar and potassium levels should be regularly checked. underlying causes for the dka should be identified. in those with severely low blood ph who are critically ill, sodium bicarbonate may be given; however, its use is of unclear benefit and typically not recommended. rates of dka vary around the world. each year, about 4% of type 1 diabetics in the united kingdom develop dka, versus 25% of type 1 diabetics in malaysia. dka was first described in 1886, and until the introduction of insulin therapy in the 1920s, it was almost universally fatal. with adequate and timely treatment, the risk of death is between <1% and 5%. signs and symptoms the symptoms of an episode of diabetic ketoacidosis usually evolve over a period of about 24 hours. predominant symptoms are nausea and vomiting, pronounced thirst, excessive urine production and abdominal pain that may be severe. in severe dka, breathing becomes rapid and of a deep, gasping character, called "kussmaul breathing". the abdomen may be tender to the point that a serious abdominal condition may be suspected, such as acute pancreatitis, appendicitis or gastrointestinal perforation. vomiting altered blood that resembles coffee grounds occurs in a minority of people and tends to originate from erosion of the esophagus. in severe dka, there may be confusion or a marked decrease in alertness, including coma. 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, a rapid heart rate and low blood pressure may be observed. often, a "ketotic" odor is present, which is often described as "fruity" or "like pear drops". the smell is due to the presence of acetone. if kussmaul respiration is present, this is reflected in an increased respiratory rate. small children with dka are relatively prone to brain swelling, also called cerebral edema, which may cause headache, coma, loss of the pupillary light reflex, and can progress to death. it occurs in about 1 out of 100 children with dka and more rarely occurs in adults. cause dka most frequently occurs in those who know they 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 (pneumonia, 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 people 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. 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". drugs in the gliflozin class (sglt2 inhibitors), which are generally used for type 2 diabetes, have been associated with cases of diabetic ketoacidosis where the blood sugars may not be significantly elevated ("euglycemic dka"). while this is a relatively uncommon adverse event, it is thought to be more common if someone receiving an sglt2 inhibitor who is also receiving insulin has reduced or missed insulin doses. furthermore, it can be triggered by severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. proposed mechanisms for sglt2-i induced "euglycemic dka" include increased ketosis due to volume depletion combined with relative insulin deficiency and glucagon excess. sglt2 inhibitors should be stopped before surgery and only recommenced when it is safe to do so. sglt2 inhibitors may be used in people with type 1 diabetes, but the possibility of ketoacidosis requires specific risk management. specifically, they should not be used if someone is also using a low carbohydrate or ketogenic diet. 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 liver (a process that is normally suppressed by insulin) from glycogen via glycogenolysis and also 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. this leads to polyuria, dehydration, and polydipsia. the absence of insulin also leads to the release of free fatty acids from adipose tissue (lipolysis), which the liver converts into acetyl coa through a process called beta oxidation. acetyl coa is metabolised into ketone bodies under severe states of energy deficiency, like starvation, through a process called ketogenesis, whose final products are aceto-acetate and β-hydroxybutyrate. these ketone bodies can serve as an energy source in the absence of insulin-mediated glucose delivery, and is a protective mechanism in case of starvation. the ketone bodies, however, have a low pka 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 with dka 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. β-hydroxybutyrate (the conjugate base of β-hydroxybutyric acid, drawn above) despite chemically containing a carboxylate group instead of a ketone, is the principal "ketone body" in diabetic ketoacidosis. 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 someone with type 2 diabetes, their condition is called "ketosis-prone type 2 diabetes". the exact mechanism for this phenomenon is unclear, but there is evidence both of impaired insulin secretion and insulin action. once the condition has been treated, insulin production resumes and often the person may be able to resume diet or tablet treatment as normally recommended in type 2 diabetes. the clinical state of dka is associated, in addition to the above, with the release of various counterregulatory hormones such as glucagon and adrenaline as well as cytokines, 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 suggest 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. diagnosis investigations diabetic ketoacidosis may be diagnosed when the combination of hyperglycemia (high blood sugars), ketones in the blood or on urinalysis and acidosis are demonstrated. in about 10% of cases the blood sugar is not significantly elevated ("euglycemic diabetic ketoacidosis"). a ph measurement is performed to detect acidosis. blood from a vein is adequate, as there is little difference between the arterial and the venous ph; arterial samples are only required if there are concerns about oxygen levels. ketones can be measured in the urine (acetoacetate) and blood (β-hydroxybutyrate). when compared with urine acetoacetate testing, capillary blood β-hydroxybutyrate determination can reduce the need for admission, shorten the duration of hospital admission and potentially reduce the costs of hospital care. at very high levels, capillary blood ketone measurement becomes imprecise. 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. 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 state (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. 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 people with diabetes for other reasons, such as poisoning with ethylene glycol or paraldehyde. the american diabetes association categorizes dka in adults 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 person 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