Short Acting Insulin

Short acting insulin is soluble (regular) human insulin, a clear zinc-stabilised formulation in which insulin forms hexamers that dissociate slowly after injection. It is the only insulin given intravenously as routine practice, and it remains the most widely available mealtime insulin in low-resource settings.

Mechanism. Identical to endogenous insulin at the receptor. Delayed hexamer dissociation sets onset 30 to 60 minutes, peak 2 to 4 hours and duration 5 to 8 hours by the subcutaneous route.

Pharmacokinetics. After intravenous injection the half-life is about 5 minutes and action ends within about 30 to 60 minutes. Doses are absorbed more slowly and erratically with larger volumes, and U500 concentrate acts as a long acting depot.

Preparations. Soluble human insulin U100, and U500 concentrate for severe insulin resistance (over 200 units daily), given 2 to 3 times daily with the dedicated U500 pen or syringe, because dosing errors with U100 devices are common.

Differences from analogues. Slower, flatter, longer; needs injecting 30 minutes before the meal and a snack 2 to 3 hours later to avoid late hypoglycaemia. HbA1c outcomes are similar to analogues in type 2 diabetes. It is the intravenous insulin of choice because it is stable in infusion systems and has a short half-life.

Mixing. Drawn up first when mixed with isophane in a single syringe (clear before cloudy), and injected straight away.

• Diabetic ketoacidosis: 0.1 units/kg/h intravenously, as 50 units in 50 mL of 0.9% sodium chloride (1 unit/mL), started once potassium is over 3.3 mmol/L. Add glucose 5 to 10% when glucose falls to about 14 mmol/L (250 mg/dL) and continue insulin until ketones are under 0.6 mmol/L and pH is over 7.3.
• Hyperosmolar hyperglycaemia: lower rate, commonly 0.05 units/kg/h, started after fluid resuscitation, aiming for a fall in glucose of no more than 5 mmol/L/h.
• Hyperkalaemia: 10 units intravenously with 25 g glucose (5 units in renal failure or low weight), with glucose checks hourly for at least 6 hours.
• Perioperative and critical care: variable rate infusion with glucose and potassium, titrated to a glucose of 7.8 to 10 mmol/L (140 to 180 mg/dL).
• Subcutaneous mealtime use: where analogues are unavailable, 30 minutes before meals, with the starting dose calculated from total daily requirements.

Special groups. Pregnancy and breastfeeding: acceptable. Children: used for ketoacidosis and where analogues are unavailable. Kidney impairment: reduce doses by 25 to 50% depending on eGFR as action is prolonged. Liver impairment: reduce doses. Regional: availability often exceeds that of analogues; storage in hot climates is the main limiting factor.

Adverse effects. Hypoglycaemia (late, 4 to 6 hours after injection), hypokalaemia on intravenous infusion, lipohypertrophy and weight gain.

Key errors. Stopping an intravenous insulin infusion in ketoacidosis without overlap (basal insulin started with the infusion, and mealtime insulin given 30 to 60 minutes before the infusion stops), confusing U500 with U100, and running an infusion without a potassium check.

Monitoring. Intravenous infusion: glucose hourly, potassium and ketones every 2 hours initially, then every 4 hours as stable. Subcutaneous use: glucose before meals and at 3 a.m. when fasting values are low.

Referral and escalation. Persistent ketoacidosis after 12 hours, insulin infusion rates over 0.2 units/kg/h without response, or recurrent hypoglycaemia.