Insulin

Insulin is indicated for patients with type 1 diabetes mellitus, patients with type 2 diabetes who are not well controlled with oral therapy. Insulin may also be required temporarily in patients with severe illness or undergoing surgery. It is given subcutaneously or intravenously (the preferred route for DKA and for peri-operative management). Hypoglycaemia is the most serious adverse effect of insulin. Insulin is available in four main types, classified by speed of onset and duration of action. Some patients may use pre-mixed insulins which contain varying proportions of short and intermediate or long acting insulins.
Types of insulin Values are hours unless otherwise specified Type of action Rapid Onset of action 5-10 minutes Peak action Duration Chemical name Drug name

30-90 minutes 2-4

Insulin lispro Insulin aspart Insulin glulisine

Humalog NovoRapid Apidra

Short

30 minutes

1-2

4-6

Soluble insulin

Actrapid Humulin S Insuman Rapid

Humulin I / Insulatard Hypurin bovine lente Lantus Levemir

Intermediate 2

3-6

18-24

Isophane insulin suspension/NPH Insulin zinc suspension

Long

1-3

Flat without a 12-24 peak

Insulin glargine Insulin detemir

In type 1 diabetes, insulin is usually initiated at 0.25-0.5 units/kg/day and titrated according to blood glucose control The choice of insulin regimen for patients should be determined by:

Compliance or resistance to injections Risk of hypoglycaemia

Lifestyle Age Complications (good control is needed to reduce the incidence of complications; however, a blind patient is unlikely to cope with injections four times a day without support from a carer).

Important points to remember with insulin

Injection technique Depth of needle penetration affects absorption of insulin:

Shallow insertion of the needle into the dermis causes pain and poor absorption Deep injection into the muscle causes pain and more rapid absorption 5-8 mm needles are appropriate for most patients - but you should avoid long needles in thin patients. The needle should be inserted perpendicular to pinched skin and the insulin should be injected over 5 to 6 seconds.

Encourage patients to rotate the place of insulin injections to reduce the incidence of skin or fat atrophy and hypertrophy. Lack of site rotation is a common cause of day to day variation in control of glucose. Insulin is absorbed:

Fastest from the abdomen Slowest from the legs and buttocks.

Other factors that affect absorption of insulin include:

Increases in skin temperature (including exercise or a hot bath), which increase absorption.

Sick day rules for insulin When patients are unwell they need to be aware of the sick day rules.

Never stop taking insulin even if not eating. There may be a need to increase the dose Test blood glucose more often (at least four times a day) Drink lots of fluids to prevent dehydration Replace normal meals with carbohydrate drinks if necessary Test urine for ketones Seek medical advice if you develop vomiting or are unsure what to do

Insulin regimens
The most commonly used insulin regimens are:

Multiple injection or basal bolus therapy

Short or rapid acting insulin is taken before each meal, long acting insulin is taken before the patient goes to bed This therapy closely mimics normal physiological insulin secretion It allows flexibility around timing of meals and exercise Snacks are needed between meals if short rather than rapid acting insulin is used Rapid acting insulin can be taken just before, rather than 30 minutes before, meals

Twice daily therapy

Injections of premixed short and intermediate acting insulin are taken before breakfast and before the evening meal This therapy is usually mixed as 30% short acting insulin and 70% intermediate acting insulin. Two thirds of the total dose is taken at breakfast time This therapy is useful for patients who are reluctant to inject frequently Regular meals and snacks are needed to prevent daytime hypoglycaemia. Nocturnal hypoglycaemia is common

Three times daily therapy

This is an injection of premixed short and medium acting insulin before breakfast, short acting insulin before the evening meal, and intermediate acting insulin before bed It can be considered if twice daily therapy does not maintain control, or if the patient has frequent nocturnal hypoglycaemia

Insulin glargine and insulin detemir

Insulin glargine (Lantus) and insulin detemir (Levemir) are basal insulin analogues that have a more predictable pharmacodynamic profile than intermediate acting insulins (Isophane/NPH). Their action profiles tend to be smoother and more prolonged (up to 24 hours), which makes them suitable as the basal component of multiple injection therapy. They are particularly useful for patients who have:

Frequent nocturnal hypoglycaemia using NPH A high fasting blood glucose despite maximum tolerated doses of NPH Variable blood sugar control on standard insulin therapy.

Insulin detemir shows less variability of absorption than NPH and glargine. However, detemir is often required twice daily, whereas glargine is needed only once daily. It does seem, however, to be associated with less weight gain.

Diabetes and surgery

The following regimen is suitable when a patient with type 1 diabetes requires intravenous infusion of insulin for 12 hours or longer (usually for major surgery).: Reduce usual insulin by to 1/3 on the night before the operation and omit morning insulin. Ideally the patient should be first on the list Early on the day of the operation, start an intravenous infusion of dextrose 5% containing potassium chloride 20 mmol/litre (provided that the patient is not hyperkalaemic) and infuse

at 100 mL per hour); make up a solution of soluble insulin 1 unit/mL in sodium chloride 0.9% and infuse intravenously using a syringe pump piggy-backed to the intravenous infusion. Infusion of dextrose is critical to avoid hypoglycaemia. The rate of the insulin infusion will vary according to patient characteristics but a typical sliding scale used in the ORH is: o o o o o Capillary glucose < 4 mmol/litre, 0 units/hour Capillary glucose 4.1-6.0 mmol/litre, 1 unit/hour Capillary glucose 6.1-8.0 mmol/litre, 2 units hour Capillary glucose 8.1-10 mmol/litre, 3 units/hour Capillary glucose > 10 mmol/litre 4 units.hour

o If CG >10 for 4 hours request prescriber up-titrates the insulin scale Aim for blood glucose of 4-10 mmol/l intra-operatively Post-operatively: Check capillary blood test postop and then every 2 hours (hourly if uncontrolled) Check U&Es and lab blood glucose daily while on the infusion Continue the infusion until the next meal, give S/C Actrapid or shortacting analogue (about of previous daily dose) 20 minutes before the meal Stop IV insulin and dextrose 30 60 minutes after S/C injection

(Note that in diabetic keto-acidosis, insulin is usually given as an intravenous infusion of soluble in insulin in a fixed dose of 0.1unit/kg until the PH is >7.3: a sliding scale is NOT used in this situation.)