Endocrinology & Metabolic

Diabetic Ketoacidosis

Insulin deficiency lets the liver overproduce glucose and acidic ketone bodies at once, giving hyperglycaemia, ketonaemia and a high-anion-gap metabolic acidosis on top of profound osmotic dehydration.

Definition

Diabetic ketoacidosis requires all three of hyperglycaemia, ketonaemia and acidosis. Glucose above 11 mmol/L, or known diabetes at any level. Blood ketones above 3 mmol/L, or urine ketones 2+ or more. Venous pH below 7.3 and/or bicarbonate below 15 mmol/L.

Epidemiology

Commonest in type 1 diabetes and often its first presentation, but roughly a third of adult episodes occur in type 2. UK incidence peaks between ages 18 and 24. Precipitants: infection, missed insulin, new diagnosis, acute illness and SGLT2 inhibitors.

Pathophysiology

Insulin deficiency with a surge in counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone) drives gluconeogenesis, glycogenolysis and unrestrained lipolysis. The liver converts free fatty acids into acetoacetate and beta-hydroxybutyrate, acids that generate a high-anion-gap metabolic acidosis. Glucose above the renal threshold causes an osmotic diuresis; vomiting and reduced intake compound the losses.

First principles

Insulin is given to switch off ketogenesis, not to lower glucose

Glucose and ketones rise for the same reason, so both fall once insulin is restored. Ketone clearance is the endpoint. A fixed-rate infusion, a set weight-based rate that ignores the glucose reading, runs on until ketonaemia resolves. If glucose normalises first, feed the insulin with glucose rather than stopping it.¹

The acidosis is high-anion-gap, and that is what you measure

Ketone bodies are acids, so unmeasured anions accumulate and the anion gap widens. The gap is (sodium plus potassium) minus (chloride plus bicarbonate); above 16 marks severe disease. Kussmaul breathing, a deep sighing hyperventilation, blows off carbon dioxide to compensate. A venous gas answers the question; arterial sampling adds nothing.¹

Serum potassium lies about total body potassium

Osmotic diuresis and vomiting strip potassium from the body, while acidosis and insulin deficiency push what remains out of the cells. The presenting result reads normal or high over empty stores. Insulin reverses that shift within the hour, so potassium goes into the fluid from the second litre, not once a low result appears.¹

Fluids before insulin, and the reason is perfusion

The deficit is litres. Restoring circulating volume improves tissue and renal perfusion and dilutes glucose before any insulin is given. Insulin into an underfilled circulation drives glucose, water and potassium into cells and can drop the blood pressure further. The order is a safety sequence.^1,2

Presentation

Hours to days of polyuria, polydipsia, weight loss, vomiting and abdominal pain in a known or new diabetic. Examination shows dehydration, tachycardia, Kussmaul (deep sighing) breathing, a pear-drop acetone smell and, when severe, drowsiness.¹

Cardinal features

Polyuria and polydipsia over preceding days
Nausea, vomiting and abdominal pain
Kussmaul (deep, sighing) breathing
Acetone (pear-drop) breath odour
Dry mucous membranes, reduced skin turgor, tachycardia
Drowsiness or confusion when severe

Red flags

Drowsiness, confusion or any fall in Glasgow Coma Scale score
Hypotension persisting after the first 500 mL fluid bolus
Persistent vomiting with aspiration risk
No urine passed by 60 minutes
Falling oxygen saturation
An untreated precipitant such as sepsis or myocardial infarction

Investigations

Capillary or venous blood glucose

One arm of the triad, then hourly, to time the switch to glucose-containing fluid.

Expected finding: Above 11 mmol/L, or any level in known diabetes. Send a laboratory glucose if the meter reads above 20 mmol/L or 'HI'. A normal glucose does not exclude DKA, especially on a sodium-glucose co-transporter 2 (SGLT2) inhibitor.

^1,3

Capillary blood ketones (beta-hydroxybutyrate)

Demonstrates the ketogenesis that defines DKA, and tracks response and resolution.

Expected finding: Above 3 mmol/L, or urine ketones 2+ or more. Blood ketones are preferred: urine ketones persist after DKA has resolved.

^1,2

Venous blood gas

Quantifies the acidosis, completes the triad and sets severity.

Expected finding: Venous pH under 7.3, bicarbonate under 15 mmol/L, or both. Potassium comes off the same sample, which is why the gas is repeated rather than a formal U&E.

U&E, particularly potassium

Sets the potassium band for the fluid prescription and detects dehydration-related acute kidney injury.

Expected finding: Potassium often normal or high despite total body depletion. Hold it between 4.0 and 5.5 mmol/L, rechecking hourly if outside that range. Get an ECG: potassium shifts cause arrhythmia.

^1,2

Precipitant screen

DKA is nearly always triggered: infection, missed insulin, new diagnosis, myocardial infarction, pancreatitis, surgery or an SGLT2 inhibitor.

Expected finding: FBC, blood cultures, urinalysis, chest radiograph and pregnancy test as indicated. A raised white cell count is common in DKA itself and does not prove infection.

^1,2

Management

Step	Detail	Source
Immediate assessment and monitoring	Nurse in a monitored bed. Two large-bore cannulae, then ABCDE (airway, breathing, circulation, disability, exposure). Send venous gas, U&E, glucose, ketones, FBC, blood cultures and ECG. Glucose and ketones hourly; venous pH, bicarbonate and potassium at 60 minutes, 2 hours, then 2-hourly.^1,2	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Restore circulating volume before insulin	Systolic BP below 90 mmHg: 0.9% sodium chloride 500 mL IV over 10 to 15 minutes, repeated if still hypotensive (most need 500 to 1000 mL). Otherwise 1 L over the first hour, then 1 L each over 2, 2, 4, 4 and 6 hours. Reassess at 12 hours. Prescribe on your trust's DKA chart.^1,2	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Start the fixed-rate intravenous insulin infusion	Once fluid is running, make 50 units human soluble insulin (Actrapid or Humulin S) up to 50 mL with 0.9% sodium chloride. Infuse at 0.1 units/kg/hour, so 7 mL/hour at 70 kg. No priming bolus. Continue usual long-acting basal insulin, or start one at 0.25 units/kg subcutaneously daily if newly diagnosed.^1,2	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Replace potassium by band	Insulin drives potassium into cells within the hour. Above 5.5 mmol/L: none. 3.5 to 5.5 mmol/L and passing urine: 40 mmol/L of infusate, ready-mixed. Below 3.5 mmol/L: senior review, because more is needed than a standard bag delivers. Do not give bicarbonate or phosphate routinely.^1,2	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023 and NICE NG17
Add glucose below 14 mmol/L and chase the targets	Run 10% glucose at 125 mL/hour alongside the sodium chloride through a Y connector, and consider reducing insulin to 0.05 units/kg/hour. Targets: ketones falling at least 0.5 mmol/L/hour, bicarbonate rising 3.0 mmol/L/hour, glucose falling 3.0 mmol/L/hour. If missed, check pump and line, then increase insulin by 1 unit/hour hourly.¹	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Grade severity and escalate	Severe DKA is any of: ketones above 6 mmol/L, bicarbonate below 5 mmol/L, pH below 7.0, potassium below 3.5 mmol/L, GCS below 12. Also oxygen saturation below 92% on air, systolic BP below 90 mmHg, pulse above 100 or below 60, anion gap above 16. Any one: consultant review, cardiac monitoring, level 2 (high dependency) care.¹	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Treat the precipitant and pre-empt treatment complications	Treat the precipitant you find. Assess venous thromboembolism and bleeding risk on admission. If VTE risk outweighs bleeding risk, give prophylactic low molecular weight heparin (LMWH) for at least 7 days; do not make this automatic for every DKA presentation. Keep urine output above 0.5 mL/kg/hour; catheterise if none by 60 minutes. Nasogastric tube if obtunded or vomiting. Falling GCS: urgent imaging, and treat cerebral oedema on critical care advice without waiting.^1,2,4	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023, NICE NG17 and NICE NG89
Confirm resolution and convert to subcutaneous insulin	Resolution is blood ketones below 0.6 mmol/L with venous pH above 7.3. Do not judge it on bicarbonate: large-volume 0.9% sodium chloride causes a hyperchloraemic acidosis that holds it down. Once eating, give subcutaneous rapid-acting insulin with a meal and stop the infusion 30 to 60 minutes later.¹	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023
Euglycaemic DKA and SGLT2 inhibitors	A normal or barely raised glucose does not exclude DKA (euglycaemic DKA). If glucose is already below 14 mmol/L, start the 10% glucose immediately and still run insulin at 0.1 units/kg/hour. Stop any SGLT2 inhibitor at once and report it on a Yellow Card (the UK adverse drug reaction scheme). Do not restart unless another cause is found and resolved.^1,3	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023 and Medicines and Healthcare products Regulatory Agency (MHRA) Drug Safety Update, April 2016
Before discharge	Refer to the diabetes team on admission and ensure review within 24 hours. Cover sick-day rules, injection technique, a home ketone meter and an out-of-hours number. Newly diagnosed diabetes needs specialist review before discharge, with a care plan copied to the GP.¹	Joint British Diabetes Societies for Inpatient Care (JBDS-IP), JBDS 02, March 2023

Illustrations

Insulin deficiency driving DKADiagram showing absolute insulin deficiency simultaneously permitting unrestrained hepatic glucose output and unopposed lipolysis with hepatic ketogenesis.PassFinals · original

Kussmaul breathing and clinical signsIllustration of the deep, sighing respiratory pattern, dehydration and acetone breath odour seen in diabetic ketoacidosis.PassFinals · original

Fluid, insulin and potassium treatment timelineChart showing the sequence and interaction of intravenous fluids, fixed-rate insulin infusion and potassium replacement over the first 24 hours.PassFinals · original

Differentials

Hyperosmolar hyperglycaemic state

Very high glucose with minimal ketones or acidosis, usually in type 2 diabetes.

Lactic acidosis

High lactate without significant ketones.

Alcoholic or starvation ketoacidosis

Ketosis with a normal or low glucose. Measure beta-hydroxybutyrate, not urine ketones.

Other high-anion-gap acidosis

Toxic alcohols, salicylate or uraemia.

Sepsis

Systemic infection, which is also a common DKA precipitant.

Complications

Hypokalaemia and arrhythmia
Cerebral oedema (mainly children and young adults)
Aspiration
Venous thromboembolism
Hypoglycaemia and hypophosphataemia from treatment
The precipitating illness

Prognosis

UK mortality is below 1%, but DKA is the leading cause of death in people under 58 with type 1 diabetes. Adult deaths follow severe hypokalaemia, respiratory distress syndrome and the precipitant; cerebral oedema is commonest in children. Most episodes resolve within 24 hours.

Guidelines

JBDS 02: The Management of Diabetic Ketoacidosis in Adults (Joint British Diabetes Societies for Inpatient Care (JBDS-IP))
NICE NG17: Type 1 diabetes in adults: diagnosis and management (National Institute for Health and Care Excellence)
NICE NG89: Venous thromboembolism in over 16s (National Institute for Health and Care Excellence)
Drug Safety Update: SGLT2 inhibitors and the risk of diabetic ketoacidosis (Medicines and Healthcare products Regulatory Agency)

References

Joint British Diabetes Societies for Inpatient Care (JBDS-IP), The Management of Diabetic Ketoacidosis in Adults, revised March 2023 (JBDS 02)
NICE, Type 1 diabetes in adults: diagnosis and management (NG17)Published 26 Aug 2015 | Updated 17 Aug 2022
Medicines and Healthcare products Regulatory Agency (MHRA), SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis (Drug Safety Update)Published 18 Apr 2016
NICE, Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism (NG89)Published 21 Mar 2018 | Updated 13 Aug 2019

Evidence checked: 2026-08-18

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.