Diabetic KetoAcidosis (DKA)

Diabetic Ketoacidosis (DKA) is a serious complication of type 1 diabetes and, less commonly, of type 2 diabetes. DKA happens when there is not enough insulin in the body to process high levels of glucose in the blood. DKA is less common in type 2 diabetes as insulin levels usually don’t drop quite so low.

Diabetic Ketoacidosis should not be confused with ketosis. Ketosis can occur as a result of a very low carbohydrate diet or fasting, and is harmless.

DKA may be the first sign of type 1 diabetes, in (so-far) undiagnosed individuals. It is estimated that diabetic ketoacidosis is the first presentation of type 1 diabetes in a quarter of the people who develop DKA.¹

If left untreated DKA can lead to coma or death and hence should always be considered a medical emergency.

Signs and symptoms

Symptoms of DKA can appear rapidly and may include typical symptoms of hyperglycaemia (such as polyuria, polydipsia, fatigue) and symptoms such as abdominal pain, nausea or vomiting and dehydration.

Some patients may have Kussmaul breathing, this is a laboured, deep breathing that is often accompanied by a fruity smell of the breath.

Physical findings may also include tachycardia, hypotension, alteration in mental status, weakness and shock.²

Causes of DKA

The two most common precipitating factors to the development of diabetic ketoacidosis include infections, including gastrointestinal tract and diabetic foot infections, and inadequate or inappropriate insulin injections, such as missed injections or insulin pump failure.² Other factors contributing to the development of DKA can include stressful events, including cardiovascular or cerebrovascular events, trauma and substance abuse.³

Increased levels of counter-regulatory hormones, such as cortisol, glucagon and growth hormone can lead to a reduction in insulin levels, increased glucose output by the liver and resistance in glucose utilisation in the peripheral tissues and hence lead to glucose overload.

Insulin omission is often linked to fear of hypoglycaemia, fear of weight gain with improved metabolic control, rebellion from authority and stress related to the person having diabetes.²

Diagnosis of DKA

The diagnosis of DKA is made when ketonaemia (blood ketones greater than 3.0 mmol/L) or significant ketonuria (more than 2+ ketones on a standard urine test) is present, along with elevated blood glucose levels (>11.0 mmol/L) and metabolic acidosis.

The biochemical criteria for diagnosis of DKA are a serum glucose level >11 mmol/L (as outlined above), venous pH <7.3 or bicarbonate <15 mmol/L.

The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis (blood pH, bicarbonate, ketones) and the presence of altered mental status.⁴

The Royal Children’s Hospital Melbourne provides this table to assess the severity of the DKA in a guideline that has been adapted for state-wide use⁵:

Severity of DKA

Severity of DKA	Assessed based on the more severe of these parameters:
Venous pH	Bicarbonate (mmol/L)
Mild	<7.3	<15
Moderate	<7.2	<10
Severe	<7.1	<5

Patients with low-normal or low serum potassium concentration on admission generally have severe total-body potassium deficiency and require careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia.²

Blood versus urine ketones

The following table outlines the various levels of blood and urine ketones and the likelihood of diabetic ketoacidosis being present:

	Ketonuria	Ketonaemia	Likelihood of DKA
Negative	0 mg/dL	-ve
Trace	5 mg/dL	+/-	<0.6 mmol/L	Absent
Small	15 mg/dL	+	0.6-1.5 mmol/L	DKA not entirely excluded, consider other conditions
Moderate	40 mg/dL	++	1.6-3.0 mmol/L	DKA possible if BGL >15 mmol/L
Large	>80 mg/dL	+++ or more	>3.0 mmol/L	DKA likely

Treatment of DKA

Successful treatment of DKA requires correction of dehydration, hyperglycaemia and electrolyte imbalances as well as frequent monitoring. It is also important to identify any related precipitating events.²

In most cases regular, continuous, intravenous insulin infusion is required until the acidosis is resolved. In mild cases of DKA it is possible to treat the person with subcutaneous rapid-acting insulin analogues.²

It usually takes longer to clear ketonaemia than hyperglycaemia. Measuring blood β-OHB is the preferred method to assess ketonaemia. Assessments of urinary or serum ketone levels by the nitroprusside method should not be used as an indicator of response to therapy.²

Criteria for the resolution of DKA include glucose <11.1mmol/L, serum bicarbonate ≥15 mmol/L, and venous pH >7.3.

When the person is able to eat and drink again subcutaneous insulin should be (re-)started at the dosages they were receiving before the onset of DKA or at a dose of 0.5-0.8 units/kg/day. The subcutaneous insulin regimen should include basal (intermediate or long-acting) and bolus (regular or rapid-acting) insulin.

Prevention

Many cases of DKA can be prevented through education, better access to medical care and effective communication. Sick day management should be reviewed at least annually and should include information on:

1. When to contact the healthcare provider and how
2. Blood glucose targets and the use of supplemental short- or rapid-acting insulin   during illness
3. Means to suppress fever and treat infections
4. Initiation of an easily digestible liquid diet containing carbohydrates and salt.

Most importantly people with diabetes should be advised never to discontinue insulin and to seek medical advice early whenever there is any sign of illness.²

References:

1. Ahuja W, Kumar N, Kumar S, Rizwan A. Precipitating Risk Factors, Clinical Presentation, and Outcome of Diabetic Ketoacidosis in Patients with Type 1 Diabetes. Cureus. 2019 May 31;11(5):e4789. doi: 10.7759/cureus.4789. PMID: 31372327; PMCID: PMC6669022. https://pubmed.ncbi.nlm.nih.gov/31372327/
2. Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48. doi: 10.2337/dc06-9916. PMID: 17130218. https://diabetesjournals.org/care/article/29/12/2739/26342/Hyperglycemic-Crises-in-Adult-Patients-With
3. Shahid W, Khan F, Makda A, Kumar V, Memon S, Rizwan A. Diabetic Ketoacidosis: Clinical Characteristics and Precipitating Factors. Cureus. 2020 Oct 4;12(10):e10792. doi: 10.7759/cureus.10792. PMID: 33154858; PMCID: PMC7606188.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606188/
4. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM: Management of hyperglycemic crises in patients with diabetes (Technical Review). Diabetes Care24:131–153, 2001. https://pubmed.ncbi.nlm.nih.gov/11194218/
5. The Royal Children’s Hospital Melbourne and the Victorian Paediatric Clinical Network Clinical Practice Guide: Diabetic Ketoacidosis, last Updated November 2018 https://www.rch.org.au/clinicalguide/guideline_index/Diabetic_Ketoacidosis/#:~:text=The%20biochemical%20criteria%20for%20diagnosis,or%20Bicarbonate%20%3C15%20mmol%2FL