Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycaemic State (HHS) — Criteria and Management

Both are hyperglycaemic crises of diabetes caused by a severe relative or absolute lack of insulin together with a surge of counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone). The 2024 international consensus report describes them as two ends of a spectrum, and overlap is common: more than one-third of people with a hyperglycaemic crisis have features of both.

• DKA — insulin deficiency is profound, so lipolysis and hepatic ketogenesis run unchecked. Result: ketone bodies, acidosis, and hyperglycaemia. Classically type 1 diabetes, but type 2 is also affected.
• HHS — enough insulin remains to suppress ketogenesis, but not to control glucose. Glucose climbs, the osmotic diuresis causes profound dehydration, and osmolality rises. Classically type 2 diabetes in older adults.

Common triggers are infection (pneumonia and urinary infection are the most frequent; about half of HHS cases are infection-related), omitted insulin, new-onset diabetes, myocardial infarction, stroke, pancreatitis, and drugs such as corticosteroids, thiazides and atypical antipsychotics. SGLT2 inhibitors have become the leading cause of euglycaemic DKA.

Without insulin, adipose tissue releases free fatty acids; the liver converts them by beta-oxidation to acetoacetate, beta-hydroxybutyrate (BHB) and acetone. In acute DKA the BHB : acetoacetate ratio rises from about 1:1 to as high as 10:1. BHB is the main ketoacid, which is why the nitroprusside test misleads: it detects acetoacetate (and acetone) but not BHB, so it can under-read early and over-read as the acidosis improves. Direct blood BHB measurement is preferred. For the biochemistry see fatty-acid oxidation and ketone bodies.

Potassium is the classic trap. Acidosis and insulin lack push potassium out of cells, so the serum level is normal or high at presentation even though total-body potassium is depleted by about 3 to 6 mmol/kg (osmotic diuresis, vomiting, hyperaldosteronism). Insulin, correction of acidosis and rehydration then drive serum potassium down by 1 to 2 mmol/L within 48 hours. Giving insulin to a patient who is already hypokalaemic can cause arrhythmia, cardiac arrest and respiratory muscle weakness.

The 2024 consensus report requires all three components: (1) hyperglycaemia or known diabetes, (2) ketonaemia and (3) metabolic acidosis. The glucose cut-off was lowered from the older 250 mg/dL to 200 mg/dL (11.1 mmol/L) or a prior history of diabetes irrespective of glucose, because about 10 percent of DKA is euglycaemic.

Classic textbook cut-offs you will still meet in MCQs are glucose above 250 mg/dL, arterial pH below 7.3, bicarbonate below 15 mEq/L and ketonaemia or ketonuria, with a raised anion gap (above about 12 to 15 mEq/L). The consensus no longer recommends anion gap as a first-line criterion because large volumes of saline cause a hyperchloraemic normal-gap acidosis; see anion gap and ABG interpretation.

The 2024 ADA/EASD consensus defines HHS as plasma glucose of 600 mg/dL or more, effective osmolality above 300 mOsm/kg (or total osmolality above 320) and no significant ketoacidosis; older texts quote effective osmolality above 320. The consensus report adds that most patients have an admission pH of 7.30 or more and bicarbonate of 18 mmol/L or more, although mild ketonaemia can be present. Effective osmolality = 2 × Na + glucose/18; total osmolality adds BUN/2.8.

Fluid deficit in DKA can reach 10 to 15 percent of body weight (StatPearls) and is usually larger in HHS. Rehydration alone lowers glucose by about 50 to 70 mg/dL per hour, improves renal glucose and ketone excretion and increases insulin sensitivity, so fluids come first.

1. Start isotonic fluid (0.9 percent saline, or a balanced crystalloid such as Ringer's lactate) at 500 to 1000 mL per hour for the first 2 to 4 hours in adults without renal or cardiac compromise. Balanced fluids resolve DKA faster and cause less hyperchloraemic acidosis in recent studies; saline remains the traditional standard.
2. Then tailor to blood pressure, heart rate, urine output and sodium. Correct the estimated deficit over 24 to 48 hours; be cautious in older adults, pregnancy, and heart or kidney disease.
3. When glucose falls below 250 mg/dL (13.9 mmol/L) in DKA, add 5 to 10 percent dextrose to the saline so insulin can continue until ketones clear. Glucose usually reaches this level within 4 to 8 hours, before the acidosis has resolved.
4. 0.45 percent saline is only for a high sodium or when osmolality is not falling despite adequate fluid and insulin. An initial rise in measured sodium as glucose falls is not a reason to switch to hypotonic fluid.

Intravenous regular insulin by continuous infusion is the preferred route. Typical fixed-rate dose: 0.1 units/kg/hour. An initial 0.1 units/kg bolus is suggested only if intravenous access will be delayed. Do not start insulin until serum potassium is above 3.5 mmol/L.

Insulin stops ketogenesis and lipolysis, moves glucose and potassium into cells, and fixes the acidosis. This is why fluids plus insulin are usually enough, and why bicarbonate is rarely needed. Keep the insulin running until ketones and acidosis resolve even though glucose normalises first.

Measure potassium 2 hours after starting insulin and every 4 hours thereafter until DKA resolves. Severe hypokalaemia (2.5 mmol/L or less) during treatment has been linked to a threefold increase in mortality. Hypomagnesaemia often coexists and makes hypokalaemia hard to correct. Use lower potassium doses in renal failure and take care in HHS, where GFR is reduced by dehydration.

Bicarbonate: routine use is not recommended; it offers no outcome benefit and may cause hypokalaemia, cerebral oedema and paradoxical CNS acidosis. Consider it only if pH is below 7.0: 100 mmol of sodium bicarbonate in 400 mL of sterile water every 2 hours until pH exceeds 7.0.

Phosphate: body stores are depleted, but routine replacement is not indicated; give it only for muscle weakness with respiratory or cardiac compromise and a level below 1.0 mmol/L.

Check capillary glucose every 1 to 2 hours. Two traps here: the anion gap should not be used as a resolution criterion because a hyperchloraemic normal-gap acidosis commonly follows saline, and urine ketones should not be used because BHB converts to acetoacetate as acidosis improves, so urine ketones may stay positive. Older MCQs may still list bicarbonate 15 or more, pH above 7.3 and anion gap 12 or less (StatPearls).

Once the patient eats, transition to subcutaneous insulin and continue the infusion for about 2 hours after the first subcutaneous dose to avoid rebound ketoacidosis. Insulin-naive patients in StatPearls receive 0.5 to 0.8 units/kg/day in a multi-dose regimen. Always look for and treat the precipitant (cultures, ECG, chest film, lipase as indicated).

• Hypoglycaemia — the commonest treatment complication (about 16 to 28 percent below 70 mg/dL); prevented by dextrose at 250 mg/dL and hourly glucose checks.
• Hypokalaemia — the most dangerous; check K before insulin.
• Hyperchloraemic normal-anion-gap acidosis — after large saline volumes; may be mistaken for persistent DKA.
• Cerebral oedema — the most important cause of death in DKA, mainly in younger patients; in HHS linked to too-rapid fall in osmolality.
• Osmotic demyelination, thrombosis and acute kidney injury — acute kidney injury occurs in about half of admissions.

For the wider disease background see diabetes mellitus: diagnosis and complications, insulin and glucagon physiology and Kussmaul breathing.