Diabetic ketoacidosis in adults

What is DKA?

Diabetic ketoacidosis (DKA) is an extreme metabolic state caused by insulin deficiency. The breakdown of fatty acids (lipolysis) produces ketone bodies (ketogenesis), which are acidic. Acidosis occurs when ketone levels exceed the body’s buffering capacity (figure⇓).1 2

Diabetic ketoacidosis may follow absolute insulin deficiency or relative insulin deficiency. Relative insulin deficiency may occur in the presence of increased levels of counter-regulatory hormones such as glucagon, cortisol, and catecholamines. Insulin deficiency results in lipolysis and ketogenesis. Ketone bodies are acidic and may initially be buffered, but when levels are high enough, will result in acidosis

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How common is DKA?

Data from the UK National Diabetes audit shows a crude one year incidence of 3.6% among people with type 1 diabetes.3 In the UK nearly 4% of people with type 1 diabetes experience DKA each year,3 the number of DKA episodes per 100 patient years is 4.8,4 about 6% of cases of DKA occur in adults newly presenting with type 1 diabetes,5 and about 8% of episodes occur in hospital patients who did not primarily present with DKA.6

How does DKA present?

DKA usually develops quickly, within 24 hours. Typically, patients develop polyuria and polydipsia along with vomiting, dehydration, and, if severe, an altered mental state, including coma (box 1). Signs of the underlying cause may also be present—for example, infection.7 Abdominal pain is a common feature of DKA and may be part of the acute episode or, less often, represent an underlying cause. DKA should be considered in any unwell patient with diabetes (type 1 or type 2).

How is DKA diagnosed?

DKA is usually diagnosed in the presence of hyperglycaemia, acidosis, and ketosis. However, hyperglycaemia may not be present (euglycaemic ketoacidosis), and low levels of blood ketones (<3 mmol/L) may not always exclude a diagnosis. Clinical judgment therefore remains crucial.

Guidelines differ on the exact biochemical thresholds for diagnosis (table 1⇓).

What is the main approach to management?

The mainstay of treatment is carefully monitored delivery of intravenous fluids and insulin. Fluids correct hyperglycaemia, dehydration, and electrolyte imbalances such as hypokalaemia. Insulin reduces glucose levels and suppresses ketogenesis. This approach coupled with the treatment of the precipitating cause and appropriate patient education before discharge should in most cases result in good outcomes.

What dose of insulin?

Both the Joint British Diabetes Societies and American Diabetes Association recommend a weight based rate of delivery of 0.1 units/kg/h. An initial bolus dose of insulin is not advised, based on a randomised controlled trial that found no benefit.24

A steady delivery of low dose insulin adequately suppresses lipolysis (and thus ketogenesis). With concomitant intravenous fluids, glucose levels may normalise rapidly. However, ketoacidosis corrects more slowly: on average it takes six hours of treatment before glucose decreases to less than 14 mmol/L, compared with 12 hours before ketoacidosis is corrected.7 25 Adequate insulin should therefore continue beyond the resolution of hyperglycaemia to ensure the eradication of ketones. This has led to the shift away from a “sliding scale” that titrates insulin against glucose levels, to fixed rate intravenous insulin infusion.

How should patients be monitored?

Some of the major complications of DKA are related to its treatment (box 3). Blood glucose and potassium levels must be closely monitored and patients must have regular review, as too much insulin results in hypoglycaemia and hypokalaemia whereas not enough may fail to adequately suppress ketogenesis.

The Joint British Diabetes Societies recommend high levels of care and central venous access for those with severe DKA: people with severe metabolic derangement (pH <7.1, bicarbonate <5 mmol/L, blood ketones >6 mmol/L or hypokalaemia on admission (K+ <3.5 mmol/L)), a reduced Glasgow coma score, or haemodynamic instability. However, the guidelines are not prescriptive and people at extremes of age or with comorbidities may also require higher levels of care.

There is no substitute for careful monitoring and responding to the patient as treatment progresses.

Mortality from DKA has improved considerably, but still persists at between 3% and 5%.27 28 Death is most often associated with the precipitating illness (for example, cardiovascular disease or infection) and rates are worse with increasing age.27

When should patients transition from intravenous to subcutaneous insulin?

Patients should move to subcutaneous insulin once DKA has resolved. There is no consensus on what marks the biochemical endpoint of DKA (table 1), so transition to subcutaneous insulin is advised when patients are eating and drinking. If patients are not eating and drinking but ketones are suppressed, a variable rate intravenous insulin infusion can be considered until oral intake is resumed. Crucially in such cases, there should be overlap between intravenous and subcutaneous insulin in order to prevent any period of insulin deficiency that risks recurrent ketogenesis. UK guidance recommends continuation of intravenous insulin for at least 30-60 minutes after the initiation of subcutaneous long acting insulin. In people with established type 1 diabetes, there is some evidence that continuing subcutaneous long acting insulin throughout the admission prevents rebound hyperglycaemia,29 and local practice may vary. Transition to subcutaneous insulin is best supported by members of the specialist diabetes team in line with national guidance.

How can DKA be prevented?

Patients with established type 1 diabetes should be given as much information as possible about risk factors for DKA and how to monitor their own glucose and ketone levels. Discussions from the accompanying TweetChat (box 4) show the need for better education, as many participants were unaware of the importance of ketone testing or the difference between ketosis and ketoacidosis.

Structured educational programmes provide advice on how to avoid omitting insulin; sick day rules, including increasing insulin doses if unwell; and when to test ketones.30 They have been shown to reduce rates of DKA.31 However, such programmes are not universally offered, and uptake can be poor.32

Patients should be advised to measure their ketone levels if they are unwell as this may identify incipient ketosis, which can be dealt with by increasing insulin doses. They should be encouraged to seek medical attention if levels are increased.

Testing ketones in capillary blood has not been shown to be better for preventing DKA than urine testing.33 People with recurrent DKA may have underlying precipitants, and psychological support may be helpful.

Drugs such as sodium-glucose cotransporter-2 inhibitors should be used with caution in people at high risk of DKA, although these associations are still being elucidated.