Diabetic ketoacidosis

New-onset diabetes

First presentation of type 1 diabetes, particularly in children and young adults

Insulin omission

Missed doses, pump failure, cost or access barriers, eating disorder

Infection

Pneumonia, urinary tract infection, sepsis, gastroenteritis, dental abscess

Acute illness

Myocardial infarction, stroke, pancreatitis, trauma, surgery

Drugs

SGLT2 inhibitors (euglycaemic DKA), corticosteroids, thiazides, antipsychotics, checkpoint inhibitors

Other

Pregnancy, alcohol excess, cocaine use

• Accounts for a large share of diabetes-related hospital admissions and is the leading cause of death in children with type 1 diabetes.
• Roughly a quarter of new type 1 diabetes diagnoses present in DKA.
• In-hospital mortality is under 1-2% with protocolised care but far higher with delayed recognition, in the elderly and where facilities are limited.

• Type 1 diabetes, especially adolescence and young adulthood
• Previous DKA episode — the strongest single predictor
• Insulin pump use without ketone monitoring
• SGLT2 inhibitor use, particularly perioperatively or during fasting or low-carbohydrate intake
• Mental health conditions, eating disorders, substance use, social deprivation
• Limited access to insulin, glucose or ketone testing

1. 1Absolute or relative insulin deficiency removes suppression of hepatic glucose output and lipolysis.
2. 2Counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone) rise, often driven by an intercurrent illness.
3. 3Free fatty acids flood the liver and are converted to acetoacetate and beta-hydroxybutyrate.
4. 4Hyperglycaemia produces osmotic diuresis with loss of water, sodium and total-body potassium.
5. 5Ketoacid accumulation exceeds buffering capacity, giving a high anion gap metabolic acidosis.

Normal physiology → mechanism → tissue change → clinical picture

1. 1Normal physiology: insulin suppresses lipolysis and hepatic ketogenesis while promoting cellular glucose and potassium uptake.
2. 2Mechanism: insulin deficiency plus counter-regulatory excess drives unrestrained ketogenesis and gluconeogenesis.
3. 3Tissue change: osmotic diuresis depletes intravascular volume and total-body potassium, phosphate and magnesium despite a normal or high serum potassium.
4. 4Functional effect: high anion gap acidosis with compensatory Kussmaul respiration; hyperosmolality causes cerebral dehydration.
5. 5Clinical manifestation: polyuria, thirst, vomiting, abdominal pain, deep sighing breathing, ketotic breath, dehydration and drowsiness.

Ketone body profile

Beta-hydroxybutyrate predominates; nitroprusside urine tests detect acetoacetate and can under-read early and over-read during recovery

Electrolyte state

Total-body potassium deficit of 3-5 mmol/kg with normal or high measured serum potassium due to acidosis-driven shift

Sodium

Measured sodium is falsely low with marked hyperglycaemia — correct for glucose

Pancreas (type 1)

Autoimmune insulitis with beta-cell destruction and preserved alpha cells

• Polyuria, polydipsia and weight loss over days
• Nausea, vomiting and diffuse abdominal pain
• Deep sighing breathing and breathlessness
• Weakness, leg cramps, blurred vision
• Drowsiness progressing to confusion and coma

• Dehydration: dry mucosae, reduced skin turgor, tachycardia, hypotension in severe cases
• Kussmaul respiration and acetone (pear-drop) breath
• Abdominal tenderness that can mimic a surgical abdomen
• Reduced Glasgow Coma Scale score, especially with high osmolality
• Signs of a precipitant: fever, chest signs, cellulitis, foot ulcer

Typical

• Young person with days of thirst and polyuria, vomiting, abdominal pain, Kussmaul breathing, glucose 25-40 mmol/L, capillary ketones 4-6 mmol/L, pH 7.05, bicarbonate 8 mmol/L.

Atypical

• Euglycaemic DKA on an SGLT2 inhibitor: glucose only 8-12 mmol/L with marked ketosis and acidosis — easily missed
• Elderly patient with mixed DKA and hyperosmolar state and predominant confusion
• Pregnancy: DKA at lower glucose levels and with faster progression
• Abdominal pain dominant, presenting to surgeons
• Established type 2 diabetes presenting in DKA during sepsis or steroid therapy

1. 1Check capillary glucose and capillary ketones in any unwell person with diabetes — including when glucose is normal.
2. 2Take venous blood gas for pH and bicarbonate; do not delay treatment for arterial sampling.
3. 3Confirm the diagnostic triad, then calculate anion gap and corrected sodium.
4. 4Start fluids and fixed-rate insulin, and add potassium to fluids once potassium is known to be below 5.5 mmol/L.
5. 5Search actively for the precipitant: infection screen, ECG and troponin, pregnancy test, medication review including SGLT2 inhibitors.
6. 6Monitor hourly glucose and ketones, and electrolytes at 2, 4, 8, 12 and 24 hours.
7. 7Resolve DKA on ketones and acid-base status, not glucose, before converting to subcutaneous insulin with an overlap.

Hyperglycaemia

Glucose > 11 mmol/L (200 mg/dL) or known diabetes — may be normal in euglycaemic DKA

Ketonaemia

Capillary beta-hydroxybutyrate ≥ 3.0 mmol/L or significant ketonuria (2+ or more)

Acidosis

Venous pH < 7.3 and/or bicarbonate < 15-18 mmol/L

Mild

pH 7.25-7.30, bicarbonate 15-18, alert

Moderate

pH 7.00-7.24, bicarbonate 10-15, drowsy

Severe

pH < 7.00, bicarbonate < 10, stupor or coma

Immediate

• Capillary and laboratory glucose, capillary beta-hydroxybutyrate, venous blood gas, urea and electrolytes, FBC, ECG.

Metabolic assessment

• Anion gap, corrected sodium, serum osmolality, phosphate, magnesium, lactate, creatinine.

Precipitant

• Urinalysis and culture, blood cultures, chest radiograph, troponin, amylase or lipase, pregnancy test — precipitant search.

Monitoring

• Hourly glucose and ketones; electrolytes and bicarbonate at 2, 4, 8, 12 and 24 h; fluid balance and neurological observations.

After recovery

• HbA1c, islet autoantibodies and C-peptide once stable to classify diabetes type.

Hyperosmolar hyperglycaemic state

Rule in: glucose > 30 with osmolality > 320 and minimal ketones, days of onset. Rule out: significant ketonaemia with pH < 7.3.

Alcoholic ketoacidosis

Rule in: binge with poor intake, low or normal glucose, raised lactate. Rule out: high glucose with known diabetes and insulin omission.

Starvation ketosis

Rule in: mild ketosis with normal pH and bicarbonate. Rule out: pH < 7.3 with high ketones.

Lactic acidosis

Rule in: lactate > 5 with shock or metformin accumulation and low ketones. Rule out: dominant ketonaemia.

Salicylate or toxic alcohol poisoning

Rule in: raised osmolar gap, tinnitus, visual loss, mixed acid-base picture. Rule out: classic ketone-driven high anion gap with hyperglycaemia.

Acute abdomen

Rule in: persistent localised peritonism after acidosis correction. Rule out: pain resolving as DKA is treated.

Severity grading

Graded by pH, bicarbonate and mental state (mild, moderate, severe) — see diagnostic criteria

Level of care

Severe DKA, pregnancy, children, or coexisting critical illness warrant high-dependency or intensive care

Resolution

Ketones < 0.6 mmol/L, venous pH > 7.3 and bicarbonate > 15 mmol/L, with the patient eating and drinking

1. Fluids

• 0.9% sodium chloride 1 L over the first hour (faster if systolic < 90 mmHg, with reassessment)
• Then approximately 1 L over 2 h, 2 h, 4 h, 4 h and 6 h, adjusted for age, cardiac and renal status
• Switch to a glucose-containing fluid alongside saline once glucose falls below 14 mmol/L to allow insulin to continue clearing ketones

2. Insulin

• Fixed-rate intravenous insulin infusion at 0.1 units/kg/h
• Aim for ketone fall ≥ 0.5 mmol/L/h, bicarbonate rise ≥ 3 mmol/L/h and glucose fall ~3 mmol/L/h
• Continue any usual long-acting basal insulin — do not stop it
• Increase the fixed rate if ketones are not falling adequately

3. Potassium

• Potassium > 5.5 mmol/L: no potassium in this bag
• Potassium 3.5-5.5 mmol/L: 40 mmol/L of infused fluid
• Potassium < 3.5 mmol/L: senior review, higher-rate replacement via an appropriate line with cardiac monitoring

4. Supportive

• Treat the precipitant — antibiotics for infection, management of myocardial infarction
• Thromboprophylaxis, nasogastric tube if vomiting with reduced consciousness, catheter if anuric
• Bicarbonate is not routinely indicated even with severe acidosis; discuss with critical care in extremis
• Phosphate replacement only if severe depletion with weakness or respiratory compromise

5. Recovery and transition

• Convert to subcutaneous insulin only after DKA resolution and when eating, overlapping the infusion with short-acting insulin
• Diabetes specialist team review before discharge in every case
• Structured education on sick-day rules, ketone testing and pump troubleshooting
• Hold SGLT2 inhibitors and review whether to restart

Insulin (IV soluble)

Fixed rate 0.1 units/kg/h; do not stop until ketones < 0.6 and acidosis corrected

Basal insulin (e.g. glargine)

Continue usual dose throughout to prevent rebound ketosis after the infusion stops

Potassium chloride

40 mmol/L in maintenance fluid when potassium is 3.5-5.5; monitor with ECG

SGLT2 inhibitors (e.g. empagliflozin)

Withhold during acute illness and around surgery — cause euglycaemic DKA

Metformin

Withhold during acute illness, dehydration or renal impairment; restart when eating and renal function is stable

Sodium bicarbonate

Not routine; potential harm including hypokalaemia and paradoxical CNS acidosis

Treatment-related

• Hypokalaemia with arrhythmia — the leading treatment-related cause of death.
• Hypoglycaemia from failing to add glucose-containing fluid.
• Cerebral oedema, especially in children with rapid osmolality shifts.
• Fluid overload and pulmonary oedema in the elderly or those with heart failure.

Disease-related

• Acute kidney injury, venous thromboembolism, aspiration pneumonia, rhabdomyolysis, ARDS.
• Persistent hyperchloraemic acidosis after large-volume saline — expected and self-limiting.

Longer term

• Recurrent DKA, insulin omission behaviour, psychological distress and diabetes distress.

• Mortality is below 1-2% with protocolised care but rises steeply with age, severe acidosis, coma and a serious precipitant.
• Most episodes resolve within 24 hours of correct treatment.
• Recurrent DKA carries a markedly worse long-term outlook and signals an unmet psychosocial or access need.
• Cerebral oedema is rare in adults but the main cause of death in children with DKA.

• Sick-day rules: never stop insulin, increase monitoring, check ketones, maintain carbohydrate and fluids
• Home capillary ketone meters for everyone with type 1 diabetes and for pump users
• Withhold SGLT2 inhibitors during illness, fasting, low-carbohydrate diets and before surgery
• Address insulin access, cost and supply barriers
• Mental health and eating disorder support in recurrent presenters
• Structured education after every episode with specialist follow-up

• Diabetes specialist nurse and physician review before discharge without exception
• Early outpatient review within 1-2 weeks; earlier for recurrent DKA
• Recheck HbA1c, renal function and classification testing (antibodies, C-peptide) as needed
• Review technology options: continuous glucose monitoring, pump settings, alarm strategy
• Document the precipitant and a written personalised sick-day plan

Children and adolescents

Use paediatric protocols with slower fluid correction and hourly neurological observations — cerebral oedema risk

Pregnancy

Occurs at lower glucose values and progresses faster; joint obstetric and critical care management with fetal monitoring

Elderly

Cautious fluid rates, frequent reassessment, higher mortality, often mixed with hyperosmolar features

CKD or dialysis

Reduced fluid volumes, meticulous potassium management, early nephrology involvement

Heart failure

Slower fluid replacement with close monitoring for pulmonary oedema

SGLT2 inhibitor users

Diagnose on ketones and pH — do not be reassured by a normal glucose

• ADA Standards of Care 2025 — hyperglycaemic crises
• National inpatient diabetes care guidance for DKA management

• Balanced crystalloids may resolve DKA marginally faster than 0.9% saline and cause less hyperchloraemic acidosis.
• Subcutaneous rapid-acting insulin protocols are effective in mild-to-moderate DKA where critical care capacity is limited.
• Recognition of SGLT2 inhibitor-associated euglycaemic DKA has driven perioperative and sick-day withholding advice.

• ADA Standards of Care in Diabetes 2025 (guideline, USA).
• DrZep editorial summary, demo dataset v0.1.