Diabetic ketoacidosis and hyperosmolar hyperglycaemic state

Definitions. DKA = hyperglycaemia + ketonaemia + metabolic acidosis (classically glucose >250 mg/dL, pH <7.30, HCO₃ <18 mEq/L, ketones positive). HHS = marked hyperglycaemia (usually >600 mg/dL) with raised effective osmolality and profound dehydration, but no significant ketosis or acidosis. Both are the metabolic comas of diabetes.

Which one occurs in whom. HHS is the characteristic emergency of the older person with type 2 diabetes; DKA is classically type 1 but occurs in older type 2 patients under severe physiological stress. Overlap syndromes are common in the elderly — up to a third have mixed features.

Precipitants. Infection is the commonest — urinary tract infection and pneumonia — followed by myocardial infarction, stroke, sepsis, non-adherence or omission of insulin, newly diagnosed diabetes, and drugs: corticosteroids, thiazides, atypical antipsychotics and SGLT2 inhibitors (euglycaemic DKA).

Why older adults do worse. A blunted thirst mechanism, raised osmotic threshold for thirst, impaired urinary concentrating ability, reduced free water clearance and dependence on carers for fluids mean that dehydration is deeper and better tolerated symptomatically before presentation. Mortality in HHS is several-fold higher than in DKA and is driven largely by the precipitating illness.

Clinical features. Common to both — polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension. DKA: Kussmaul respiration, acetone breath, abdominal pain, vomiting, developing over hours. HHS: insidious over days to weeks, with altered sensorium, focal neurological deficits mimicking stroke, seizures and coma. In the older adult, delirium or a fall may be the only presentation.

Investigations. Capillary and laboratory glucose, blood β-hydroxybutyrate (preferred to urine ketones), venous or arterial blood gas, urea, creatinine and electrolytes, corrected sodium (add 1.6 mEq/L per 100 mg/dL glucose above 100), effective osmolality = 2 × Na⁺ + glucose/18, anion gap, full blood count, CRP, blood and urine cultures, chest radiograph and ECG (silent myocardial infarction).

Fluids are the first priority. Start 0.9% sodium chloride. In older adults with cardiac or renal disease, use slower, more cautious rates with close monitoring of jugular venous pressure, chest and urine output. HHS requires a larger total fluid deficit to be replaced but more slowly, aiming to lower osmolality by no more than 3–8 mOsm/kg/h to avoid cerebral oedema.

Insulin. DKA — fixed-rate intravenous insulin infusion at 0.1 units/kg/h. HHS — insulin is started at a lower rate (0.05 units/kg/h) and only after fluids alone have stopped lowering the glucose, since fluid alone corrects much of the hyperglycaemia. Target a fall of 50–70 mg/dL/h; add 5–10% dextrose when glucose reaches ~250 mg/dL in DKA or ~300 mg/dL in HHS, continuing insulin to clear ketones.

Potassium and other electrolytes. Total body potassium is always depleted despite a normal or high initial level. Withhold insulin if K⁺ <3.3 mEq/L until potassium is replaced; add potassium once K⁺ <5.3 mEq/L with adequate urine output. Bicarbonate only if pH <6.9. Phosphate only for severe depletion (<1 mg/dL) with cardiac or respiratory muscle weakness.

Complications and resolution. Iatrogenic hypokalaemia, hypoglycaemia, fluid overload and pulmonary oedema (especially in the elderly), hyperchloraemic acidosis, venous thromboembolism — give prophylactic low-molecular-weight heparin, particularly in HHS — aspiration, AKI, and rarely cerebral oedema. DKA has resolved when ketones have cleared with pH ≥7.3 or HCO₃ ≥18 mEq/L; HHS has resolved when osmolality is normal, urine output adequate and mental status has returned to baseline.

ADA/EASD/JBDS/AACE/DTS 2024 Consensus Report on Hyperglycaemic Crises — new diagnostic criteria. DKA now requires the "DKA triad": D — glucose ≥200 mg/dL (lowered from 250) or any prior history of diabetes irrespective of glucose; K — β-hydroxybutyrate ≥3.0 mmol/L or urine ketones ≥2+; A — pH <7.3 and/or HCO₃ <18 mmol/L. The anion gap has been removed from both the diagnostic and the resolution criteria (it is distorted by hyperchloraemia from saline). HHS now requires glucose ≥600 mg/dL, effective osmolality >300 mOsm/kg (or total >320), β-OHB <3.0 mmol/L and pH ≥7.3 with HCO₃ ≥15. Direct measurement of β-hydroxybutyrate is strongly recommended over urine ketones. Severe DKA = β-OHB >6 mmol/L, pH <7.0, HCO₃ <10, or stupor/coma — these plus all HHS need ICU care.

SGLT2 inhibitors and euglycaemic DKA. SGLT2 inhibitors now account for the majority of euglycaemic DKA cases. Practical consequences: check ketones whenever an unwell patient on an SGLT2 inhibitor presents, whatever the glucose; apply sick-day rules — withhold the drug during acute illness, dehydration, fasting or reduced oral intake, and stop it 3–4 days before elective surgery. The 2024 consensus also recommends that CGM be offered at discharge to all patients admitted with DKA, and gives specific guidance for frail older adults.