Diabetic Emergencies

DKA

Diabetic ketoacidosis (DKA) is an acute metabolic emergency caused by absolute or relative insulin deficiency with excess counter-regulatory hormones, producing ketonaemia, high anion gap metabolic acidosis, osmotic diuresis and electrolyte depletion. It is classically associated with type 1 diabetes, but also occurs in insulin-deficient type 2 diabetes, pancreatogenic diabetes, pregnancy, and increasingly with SGLT2 inhibitors, where “euglycaemic DKA” may present with glucose <14 mmol/L.

Pathophysiology and diagnostic criteria

Insulin deficiency reduces peripheral glucose uptake and disinhibits hepatic gluconeogenesis and glycogenolysis; glucagon, catecholamines, cortisol and growth hormone amplify hyperglycaemia. Simultaneously, hormone-sensitive lipase increases free fatty acid flux to the liver, where mitochondrial β-oxidation generates acetoacetate and β-hydroxybutyrate. β-hydroxybutyrate predominates in severe DKA due to an increased NADH/NAD⁺ ratio; nitroprusside urine ketone tests detect acetoacetate but underestimate β-hydroxybutyrate and may paradoxically appear worse during recovery.

Parameter	Typical DKA threshold	Exam-relevant comment
Capillary/venous ketones	>3.0 mmol/L	Preferred bedside test; resolution usually <0.6 mmol/L
Venous pH	<7.30	Venous pH is acceptable; differs from arterial by approximately 0.03
Serum bicarbonate	<15 mmol/L	Reflects metabolic acidosis; monitor trend
Glucose	Usually >11 mmol/L	May be normal in pregnancy, starvation, alcohol excess, or SGLT2 inhibitor use
Anion gap	Usually >12 mmol/L	AG = Na+ + K+ − Cl− − HCO3−; albumin correction matters

Severity classification and precipitants

Severity	pH	Bicarbonate	Mental state
Mild	7.25–7.30	15–18 mmol/L	Alert
Moderate	7.00–7.24	10–14.9 mmol/L	Drowsiness possible
Severe	<7.00	<10 mmol/L	Stupor/coma more likely

Common precipitants are remembered as “5 I’s”: infection, insulin omission or pump failure, infarction, inflammation, and iatrogenic drugs. Important drug triggers include glucocorticoids, sympathomimetics, atypical antipsychotics and SGLT2 inhibitors. Initial evaluation should include capillary glucose and ketones, venous blood gas, U&E, osmolality, FBC, CRP, cultures when indicated, ECG, troponin if appropriate, and pregnancy testing in women of reproductive potential.

Management principles

Current UK practice is largely based on JBDS guidance; ADA principles are similar. Treatment priorities are cautious volume restoration, fixed-rate intravenous insulin, potassium replacement, identification of precipitant, and avoidance of cerebral oedema and hypokalaemia. DKA is a state of total body potassium depletion despite normal or high serum potassium due to acidosis and insulin deficiency shifting K⁺ extracellularly.

Intervention	Recommended approach	Key caveat
Fluid resuscitation	0.9% sodium chloride 1 L over 1 h, then further litres over approximately 4, 8, 12 and 24 h, adjusted for age, cardiac/renal disease and shock	Aim gradual fall in osmolality; corrected Na+ rises by about 2.4 mmol/L for each 5.5 mmol/L glucose rise
Insulin	Fixed-rate IV insulin infusion 0.1 units/kg/h	No routine bolus in adults; continue long-acting basal insulin to prevent rebound ketosis
Potassium	If K+ 3.5–5.5 mmol/L: add 40 mmol KCl/L fluid; if >5.5 omit initially; if <3.5 seek senior/ICU input and replace before or with reduced insulin	Insulin may precipitate life-threatening hypokalaemia
Glucose	When glucose <14 mmol/L, add 10% glucose, usually 125 mL/h, while continuing insulin	Insulin is required to clear ketones, not merely to normalise glucose
Bicarbonate	Not routine; consider only in extreme acidaemia, e.g. pH <6.9, with specialist input	Risks include hypokalaemia, paradoxical CNS acidosis and impaired oxygen unloading

Therapeutic targets include fall in ketones by ≥0.5 mmol/L/h, rise in bicarbonate by ≥3 mmol/L/h, and fall in glucose by approximately 3 mmol/L/h. If ketones are not falling adequately, check infusion delivery and escalate insulin, commonly by 1 unit/h increments or weight-based adjustment. Monitoring is typically hourly glucose and ketones, with venous blood gas and electrolytes every 2–4 hours initially.

Resolution, transition and complications

Resolution is usually defined by venous pH >7.3, bicarbonate >15 mmol/L, blood ketones <0.6 mmol/L and clinical improvement. Transition to subcutaneous insulin requires overlap: give rapid-acting insulin with meal and continue IV insulin for at least 30–60 minutes afterwards; if initiating basal insulin, overlap by 2–4 hours depending on preparation. Omission of basal insulin is a frequent cause of recurrent DKA.

Complications include hypokalaemia, hypoglycaemia, pulmonary oedema, ARDS, venous thromboembolism, aspiration, and cerebral oedema. Cerebral oedema is uncommon in adults but highly lethal; warning signs are headache, bradycardia, hypertension, reduced consciousness and seizures. High-risk situations requiring senior/critical care involvement include pH <7.0, K⁺ <3.5 mmol/L, shock, coma, pregnancy, significant comorbidity, or failure of ketone clearance. In SGLT2 inhibitor-associated DKA, stop the drug, treat with standard DKA insulin and dextrose strategy, and avoid rechallenge unless a compelling specialist-led indication exists.

HHS

Hyperosmolar hyperglycaemic state is a life-threatening decompensation of usually type 2 diabetes characterised by profound dehydration, severe hyperglycaemia and hyperosmolality with absent or only mild ketonaemia. It is particularly important in MRCP because management differs materially from DKA: the primary therapy is controlled volume replacement, while insulin is usually delayed. Mortality remains high, typically 10–20%, reflecting older age, comorbidity and precipitating illness rather than hyperglycaemia alone.

Pathophysiology and precipitants

HHS develops over days to weeks. Relative insulin deficiency is sufficient to impair peripheral glucose uptake and suppress excessive hepatic glucose output only partially, but usually adequate to inhibit hormone-sensitive lipase and ketogenesis. Marked hyperglycaemia causes osmotic diuresis, with loss of water exceeding sodium loss, leading to hypertonicity, intracellular dehydration and neurological dysfunction. Counter-regulatory hormones, infection-associated cytokines, renal impairment and reduced thirst/access to fluids amplify the process.

• Common precipitants: pneumonia, urinary sepsis, myocardial infarction, stroke, pancreatitis, trauma, surgery, missed therapy, new diabetes.
• Drug triggers: glucocorticoids, thiazides, loop diuretics, atypical antipsychotics, beta-agonists, phenytoin, calcineurin inhibitors.
• High-risk groups: frail older adults, care-home residents, dementia, CKD, heart failure, limited access to water.

Diagnosis and severity assessment

JBDS criteria emphasise clinical context rather than a single biochemical cut-off. Typical diagnostic features are glucose ≥30 mmol/L, osmolality ≥320 mOsm/kg, severe dehydration, and absence of significant acidosis: pH usually >7.30, bicarbonate >15 mmol/L, ketones <3.0 mmol/L. Mixed DKA/HHS occurs and should be treated as DKA when significant ketonaemia or acidosis is present.

Parameter	Exam-relevant interpretation
Calculated osmolality	2 × Na + glucose + urea in mmol/L; normal approximately 275–295 mOsm/kg.
Effective osmolality/tonicity	2 × Na + glucose; urea is ineffective for sustained transcellular water shifts.
Mental status	Confusion, seizures or coma are more likely when osmolality is >330 mOsm/kg, but focal signs require stroke/sepsis evaluation.
Corrected sodium	Measured Na rises by about 2.4 mmol/L for each 5.5 mmol/L fall in glucose; falling glucose with rising Na may be appropriate if osmolality is falling.

Management principles

Manage in a monitored setting; consider HDU/ICU if shock, osmolality very high, coma, acute coronary syndrome, severe renal impairment, hypokalaemia, or major comorbidity. Initial assessment should include venous/arterial blood gas, capillary ketones, U&E, osmolality calculation, FBC, cultures where indicated, ECG, troponin if appropriate, CXR and urine testing. Insert urinary catheter if accurate fluid balance is needed.

Fluid replacement

The fluid deficit is often 100–220 mL/kg. Use 0.9% sodium chloride initially because it is relatively hypotonic compared with the patient’s serum and restores intravascular volume. The aim is gradual correction: osmolality should fall by approximately 3–8 mOsm/kg/hour; glucose should fall by no more than about 5 mmol/L/hour; serum sodium should not fall by more than 10 mmol/L in 24 hours. Excessively rapid shifts risk cerebral oedema, osmotic demyelination and circulatory collapse.

• Shock: give 0.9% saline boluses, typically 500 mL over 10–15 minutes, reassessing haemodynamics; follow sepsis/cardiac protocols as appropriate.
• No shock: cautious replacement with 0.9% saline; aim for substantial positive balance in the first 12 hours, modified for heart failure, CKD and frailty.
• If osmolality is not falling despite adequate 0.9% saline and glucose is not declining, review fluid rate, renal function and ongoing losses; 0.45% saline may be considered only with senior input.
• When glucose falls below 14 mmol/L, add 5% or 10% glucose while continuing saline to permit ongoing osmolar correction without hypoglycaemia.

Insulin and potassium

Early insulin can cause abrupt intracellular glucose and water shifts, worsening hypovolaemia and precipitating vascular collapse. Therefore, do not start insulin routinely at presentation unless there is significant ketonaemia/acidosis. Start fixed-rate IV insulin only after adequate fluids, when osmolality is no longer falling with fluids alone, or if ketones are significant. The usual HHS dose is 0.05 units/kg/hour IV, lower than standard DKA dosing.

Serum K+	Action
<3.5 mmol/L	Senior/critical care review; replace potassium before insulin where possible due to arrhythmia risk.
3.5–5.5 mmol/L	Add potassium to IV fluids, commonly 40 mmol KCl/L, with ECG and renal monitoring.
>5.5 mmol/L	No potassium initially; recheck frequently as total-body potassium is usually depleted.

Monitoring and complications

Check capillary glucose hourly initially; U&E, venous pH/bicarbonate, osmolality and potassium every 2–4 hours depending on severity. Track neurological status and fluid balance closely. Treat the precipitant aggressively. Because HHS is strongly prothrombotic through haemoconcentration, hyperviscosity, endothelial activation and immobility, give prophylactic low-molecular-weight heparin unless contraindicated; use therapeutic anticoagulation only for confirmed/suspected VTE or another indication. Transition to subcutaneous insulin or oral therapy only when osmolality is <300 mOsm/kg, the patient is clinically euvolaemic, eating and the precipitant is controlled.

Hypoglycaemia

Hypoglycaemia is the commonest acute diabetic emergency and a major limiting toxicity of insulin and insulin secretagogues. For examination purposes, diagnose clinically using Whipple’s triad: compatible symptoms, low plasma glucose, and symptom resolution after glucose correction. In diabetes care, treatment should not await laboratory confirmation if capillary glucose is low or the patient is neuroglycopenic.

Definitions, staging and pathophysiology

Category	Glucose threshold	Clinical significance
Level 1 hypoglycaemia	<3.9 mmol/L (<70 mg/dL)	Alert value; counter-regulatory responses begin, treatment indicated.
Level 2 clinically significant hypoglycaemia	<3.0 mmol/L (<54 mg/dL)	Associated with impaired cognition, arrhythmia risk and recurrent hypoglycaemia.
Level 3 severe hypoglycaemia	No fixed threshold	Requires third-party assistance because of severe cognitive impairment, seizure or coma.

Normal defence against falling glucose is hierarchical: suppression of endogenous insulin at approximately 4.5 mmol/L, glucagon and adrenaline secretion at approximately 3.8 mmol/L, autonomic symptoms near 3.2–3.4 mmol/L, and neuroglycopenia below approximately 3.0 mmol/L. In long-standing type 1 diabetes there is loss of intra-islet glucagon response; repeated antecedent hypoglycaemia shifts adrenergic thresholds lower, producing hypoglycaemia-associated autonomic failure and impaired awareness. This may be precipitated by intensive control, sleep, exercise, alcohol, renal impairment or autonomic neuropathy.

Symptoms are adrenergic/cholinergic, including tremor, palpitations, sweating, hunger and anxiety, or neuroglycopenic, including confusion, diplopia, behavioural change, focal neurology, seizure and coma. Beta-blockers may blunt tremor and palpitations but sweating is often preserved. Alcohol inhibits hepatic gluconeogenesis by increasing the NADH:NAD ratio, so delayed nocturnal hypoglycaemia is typical, especially after exercise or missed carbohydrate.

Causes and risk stratification

• Therapeutic excess: excessive insulin dose, incorrect insulin type, injection into exercised limb, reduced carbohydrate intake, delayed meal, gastroparesis.
• Secretagogues: sulfonylureas, especially glibenclamide/glyburide and long-acting preparations; risk is amplified by renal impairment and older age.
• Reduced clearance: chronic kidney disease reduces insulin clearance and renal gluconeogenesis; advanced liver disease reduces glycogenolysis and gluconeogenesis.
• Increased utilisation: exercise, sepsis, pregnancy, weight loss after bariatric surgery.
• Endocrine mimics or contributors: adrenal insufficiency, hypopituitarism; consider when hypoglycaemia is recurrent or disproportionate.

Landmark trial data are frequently examined. In the DCCT, intensive therapy in type 1 diabetes reduced microvascular endpoints but approximately tripled severe hypoglycaemia. In ACCORD, targeting HbA1c <6.0% in high-risk type 2 diabetes increased mortality and severe hypoglycaemia, underpinning modern individualised targets rather than universal near-normal glycaemia.

Immediate management

Clinical state	Treatment	Key points
Conscious, able to swallow	15–20 g rapid-acting carbohydrate orally; recheck capillary glucose after 10–15 min	Examples: 150–200 mL non-diet sugary drink, 3–4 glucose tablets, glucose gel. Repeat if still <4.0 mmol/L.
Conscious but poor intake	Glucose gel 10–20 g buccally, with supervision	Avoid if reduced consciousness because of aspiration risk.
Unconscious, seizure, or unsafe swallow with IV access	IV glucose: commonly 75–100 mL of 20% dextrose or 150–200 mL of 10% dextrose	10% dextrose is less irritant; 50% dextrose causes thrombophlebitis/extravasation injury and is less favoured.
No IV access	Glucagon 1 mg IM/SC adults; 500 micrograms if <25 kg	Ineffective or delayed with depleted glycogen: starvation, alcohol excess, liver failure, adrenal insufficiency.

After recovery, give longer-acting carbohydrate, e.g. meal, toast, biscuits or enteral feed, unless the next meal is imminent. If long-acting insulin or sulfonylurea is implicated, observe for recurrence; check glucose at least hourly initially. In hospital, a dextrose infusion, commonly 10% dextrose at 100 mL/h titrated to capillary glucose, may be required. Potassium can fall after dextrose-stimulated insulin release, so monitor electrolytes in prolonged treatment.

Sulfonylurea-induced hypoglycaemia and octreotide

Sulfonylureas close pancreatic beta-cell ATP-sensitive potassium channels, causing insulin release independent of ambient glucose; recurrent hypoglycaemia after dextrose is characteristic because glucose further stimulates insulin secretion. Treat initially with IV dextrose, then suppress insulin secretion with octreotide: adults 50 micrograms SC every 6–12 h or IV in severe cases; children 1–1.5 micrograms/kg. Observe for at least 12–24 h after the last octreotide dose, longer with modified-release preparations or renal impairment. Glucagon is not ideal in sulfonylurea poisoning because it may worsen rebound insulin secretion.

Prevention and examination pitfalls

• Review insulin timing, basal-bolus ratios, carbohydrate counting, injection sites, renal function and intercurrent illness rules.
• Impaired awareness is suggested by absent autonomic warning symptoms; structured avoidance of hypoglycaemia for 2–3 weeks can partially restore awareness.
• Real-time continuous glucose monitoring reduces time in hypoglycaemia in insulin-treated diabetes; alarms should be considered for recurrent severe episodes.
• Do not discharge after severe hypoglycaemia without identifying the cause, adjusting therapy, ensuring access to rescue glucagon where appropriate, and advising driving restrictions according to local regulations.