FRCA Notes

Insulin

Resources

  • Insulin is a peptide hormone produced by pancreatic β-cells (see insulin physiology)
  • Therapeutic insulins differ little pharmacodynamically, but widely in pharmacokinetics
  • Patients with type 1 diabetes must always have a source of insulin, otherwise DKA will develop

  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus when non-insulin treatments are insufficient, or for symptomatic hyperglycaemia
  • Variable rate intravenous insulin infusion (VRII) peri-operatively and in the critically ill
  • Fixed rate intravenous insulin infusion (FRII) for DKA (0.1units/kg/hr) and HHS (0.05units/kg/hr)
  • Treatment of hyperkalaemia, given with glucose
  • High-dose insulin euglycaemic therapy in β-blocker and calcium channel blocker overdose

  • A 51 amino acid polypeptide of A- and B-chains linked by two disulphide bridges
  • Now produced as human insulin by recombinant DNA technology, replacing bovine and porcine insulin
  • Analogues have amino acid substitutions that alter their absorption from subcutaneous tissue
  • Absorption can be prolonged by:
    • Complexing with protamine (isophane/NPH) or zinc
    • Crystalline rather than amorphous preparations
    • Precipitation at physiological pH in the subcutaneous tissue (glargine)
    • Albumin binding (detemir, degludec)

  • Neutral solutions (pH 7) with a standard UK concentration of 100units/ml
    • Concentrated 200, 300 and 500units/ml preparations exist for patients with marked insulin resistance; take care with these


Type Examples Onset Peak Duration Clinical use
Rapid-acting analogues Aspart (NovoRapid), lispro (Humalog), glulisine (Apidra) 10-15mins 1hr 3-4hrs Bolus with meals; correction doses; CSII
Short-acting soluble Actrapid, Humulin S 30mins 1-3hrs 6-8hrs Intravenous infusions (VRII, FRII)
Intermediate-acting (isophane/NPH) Insulatard, Humulin I 1-2hrs 4-6hrs 8-10hrs Basal insulin, once or twice daily
Long-acting analogues Glargine (Lantus), detemir (Levemir), degludec (Tresiba) 1-2hrs Peakless 18-36hrs Basal insulin, usually once daily
Biphasic (mixed) NovoMix 30, Humulin M3, Humalog Mix 25 As components Two peaks As components Twice daily regimen

  • The number in biphasic insulin names is the percentage of short-acting insulin, e.g. NovoMix 30 is 30% aspart and 70% protamine-bound aspart
  • Long-acting analogues take 2-3 days to reach steady state

  • Once daily: a long- or intermediate-acting insulin, usually at night, alongside oral agents in T2DM
  • Twice daily: premixed insulin before breakfast and the evening meal
  • Basal-bolus: once (or twice) daily basal insulin with rapid-acting insulin at meals; basal insulin is ~50% of the total daily dose
  • Continuous subcutaneous insulin infusion (CSII, 'pump'): a programmable basal rate of rapid-acting insulin, with patient-delivered meal boluses
  • Hybrid closed-loop systems: a pump linked to a continuous glucose monitor that automatically adjusts basal insulin

Absorption

  • Inactive orally; given subcutaneously or intravenously
  • Subcutaneous absorption varies with site, blood flow, temperature and lipohypertrophy
  • Intravenous insulin may adsorb to plastic infusion containers and tubing

Metabolism

  • Metabolised in the liver, kidney and muscle by insulinase (glutathione insulin transhydrogenase)
  • Very short intravenous half-life of a few minutes

Excretion

  • Clearance is reduced in renal impairment, increasing the risk of hypoglycaemia

Nutritional and metabolic

  • Hypoglycaemia, from excess insulin or inadequate calorie intake
  • Hypoglycaemic unawareness with long-standing insulin-treated diabetes
  • Hypokalaemia, from intracellular potassium shift
  • Weight gain

Other

  • Lipohypertrophy and lipoatrophy at injection sites
  • Immunogenicity, mainly with animal insulins

  • Insulin is a recognised cause of iatrogenic harm, prompting National Patient Safety Agency guidance:
    • Prescribe by brand name
    • Write 'units' in full; never use 'U' or 'IU'
    • Measure doses with an insulin syringe or pen, never an intravenous syringe
    • Use ready-made infusions where possible, e.g. prefilled syringes of 50units in 50ml 0.9% saline

  • Never withhold insulin from a patient with type 1 diabetes
  • Allow self-management of insulin in hospital where possible

Perioperative management


Subcutaneous insulin

  • Patients missing no more than one meal can usually be managed by modifying their usual insulin, avoiding the risks of a VRII

Regimen Day before surgery Day of surgery
Once daily long-acting, evening Give 80% of the usual dose Check CBG on admission
Once daily long-acting, morning No change Give 80% of the usual dose
Twice daily long-acting Give 80% of the evening dose Give 80% of the morning dose; evening dose unchanged
Twice daily premixed No change Halve the morning dose; evening dose unchanged
Basal-bolus No change Omit rapid-acting insulin with missed meals; basal as above
Three times daily premixed No change Halve the morning dose; omit the lunchtime dose

Variable rate intravenous insulin infusion

  • Consider a VRII only if there is metabolic derangement or more than one meal will be missed
  • Identify these patients pre-operatively so the VRII can be established on admission
  • Continue long-acting basal insulin at 80% of the usual dose alongside the VRII
  • Run a glucose-containing substrate fluid concurrently; never stop the substrate while insulin is running
    • Dextrose 4% in 0.18% saline with 0.15 or 0.3% KCl at 25-30ml/kg/day (Association of Anaesthetists and JBDS-IP, 2026)
    • Previous guidance recommended 5% glucose in 0.45% saline with KCl; no single fluid meets all requirements
    • Check U&E daily given the risk of hyponatraemia
  • Check CBG hourly

Insulin pumps and wearables

  • Agree a multidisciplinary plan before surgery
  • A CSII can be continued if there will be only one missed meal, the patient can self-manage, and the pump can be sited away from the surgical field and diathermy
  • Use Teflon, not steel, cannulae
  • All wearable devices must be removed for MRI

  • Target CBG 6-10mmol/L in patients on insulin
  • Check CBG hourly on a VRII; continuous glucose monitors are not reliable under anaesthesia so must be supplemented with capillary measurements

  • Hypoglycaemia: intervene if CBG <6mmol/L in patients on insulin, as anaesthesia masks symptoms; give intravenous glucose e.g. 15-20g and recheck after 15mins
  • Hyperglycaemia (>10-12mmol/L): check ketones, then give a correction dose of rapid-acting insulin
    • Intravenous correction is preferred intra-operatively owing to unreliable subcutaneous perfusion
    • Avoid repeating subcutaneous doses within 2-3hrs ('insulin stacking')
    • The patient's correction factor (expected fall in mmol/L per unit) can be estimated as 100 ÷ total daily dose

  • Dexamethasone for PONV prophylaxis is acceptable as it only raises glucose modestly

  • Ensure a documented handover including oral intake, the ongoing need for VRII and when to restart usual insulin
  • Never disconnect a VRII during transfers
  • In type 1 or insulin-requiring diabetes, only stop a VRII once subcutaneous basal insulin has been given, CBG is <10mmol/L and ketones are <0.6mmol/L
  • A basal-bolus regimen achieves better control than a sliding scale of short-acting insulin alone
  • Measure ketones if two consecutive CBG readings are >13mmol/L
  • Return to self-management as soon as possible, and remind patients of sick day rules