DIABETIC KETOACIDOSIS ( DKA)
In people without diabetes, insulin helps sugar enter the cells, which use it for fuel. A person with diabetes does not make enough insulin to properly transport the sugar, which means that their body cannot use it for energy.
Without enough sugar, the liver turns some of the fat in the body into acids called ketones. Ketones build up in the bloodstream and spill over into the urine. When these excess ketones get into the blood, the blood becomes acidic, causing DKA.
DKA is a medical emergency. Anyone living with diabetes needs to learn the signs and symptoms of DKA to know when to seek urgent medical treatment.
DKA IN TYPE 1 VS TYPE 2 DIABETES
DKA is much more likely to occur in people with type 1 diabetes, but anyone with type 1 or type 2 diabetes can develop it. Those who need to take insulin have a more severe form of diabetes and, therefore, will have a higher risk of DKA.
- older people
- people who are overweight
- people from non-white ethnic groups
Diabetic ketoacidosis symptoms often start suddenly and can include:
- excessive thirst
- frequent urination
- abdominal pain and discomfort
- rapid breathing
- a flushed face
- fruity-smelling breath
- dry mouth and skin
- intravenous (IV) fluid replacements
- IV insulin drip until blood sugar levels drop to within an acceptable range
- IV electrolyte replacements very high blood sugar levels and low levels of insulin cause diabetic ketoacidosis. Either illness or a problem with insulin therapy can put a person at risk of having high blood sugar or low insulin, even with regular diabetes treatment. Illness and infection alter the production of some of the body’s hormones, such as cortisol and epinephrine. These hormones change how insulin works in the body and can reduce its effectiveness, which some people may need to counter by taking extra insulin while they are unwell. Problems with prescribed insulin therapy can also cause DKA. Some issues with insulin therapy that may trigger DKA include:
Other triggers for DKA can include:
- a heart attack
- a stroke
- physical trauma, such as a car accident
- emotional stress
- drug or alcohol misuse
- certain medications
People with type 1 diabetes or those who frequently miss insulin doses have the highest risk of developing DKA. Some diabetes medications may increase the risk of DKA even when the blood sugar is not high.
The treatment for DKA can sometimes cause complications. Possible complications include:
- hypoglycemia, or low blood sugar, from insulin, rapidly entering the body
- hypokalemia, or low potassium levels, from fast fluid replacement
- cerebral edema, or swelling in the brain, as a result of changing the blood sugar levels too quickly
Due to the risk of these complications, doctors will closely monitor people with DKA in the hospital.
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.
People with diabetes can monitor their own ketone levels when unwell and seek help if they are elevated.
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 unit (ICU) or similar high-dependency area or ward for close observation may be necessary.
The amount of fluid replaced depends on the estimated degree of dehydration. If dehydration is so severe as to cause shock (severely decreased blood pressure 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.
Normal saline (0.9% saline) has generally been the fluid of choice. There have been a few small trials looking at balanced fluids with few differences.
Special but unusual consideration is cardiogenic shock, where the blood pressure is decreased not due to dehydration but due to the 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.
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 administered. It is possible to use rapid-acting insulin analogs injections under the skin for mild or moderate cases.
In general, insulin is given at 0.1 unit/kg per hour to reduce 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 levels can fluctuate severely during the treatment of DKA because insulin decreases potassium levels in the blood by redistributing it into cells via increased sodium-potassium pump activity. 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 the 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 hypokalemia.
The administration of sodium bicarbonate 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, 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 mannitol and hypertonic saline (3%) are used—as in some other forms of cerebral edema—in an attempt to reduce the swelling.
The resolution of DKA is defined as a 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 the blood (<1 mmol/l) or urine. Once this has been achieved, insulin may be switched to the usual subcutaneously administered regimen, one hour after which the intravenous administration can be discontinued.
In people with suspected ketosis-prone type 2 diabetes, the 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 withdraw insulin and attempt treatment with oral medication as in type 2 diabetes. Generally speaking, routine measurement of C-peptide as a measure of insulin production is not recommended unless there is genuine doubt as to whether someone has type 1 or type 2 diabetes.
Diabetic ketoacidosis occurs in 4.6–8.0 per 1000 people with diabetes annually. Rates among those with type 1 diabetes are higher with about 4% in the United Kingdom developing DKA a year while in Malaysia the condition affects about 25% a year. In the United States, 135,000 hospital admissions occur annually as a result of DKA, at an estimated cost of $2.4 billion or a quarter to a half the total cost of caring for people with type 1 diabetes. There has been a documented increasing trend in 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. Lower socioeconomic status and higher area‐level deprivation are associated with an increased risk of diabetic ketoacidosis in people with diabetes mellitus type 1.
Previously considered universally fatal, the risk of death with adequate and timely treatment is around 1–4%. Up to 1% of children with DKA develop a complication known as cerebral edema. Rates of cerebral edema in US children with DKA has risen from 0.4% in 2002 to 0.7% in 2012. Between 2 and 5 out of 10 children who develop brain swelling will die as a result.
The first full description of diabetic ketoacidosis is attributed to Julius Dreschfeld, 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 percent, and by the 1950s it had become less than 10 percent. 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.