1. Ceri Jones Diabetes Nurse Facilitator 2013
INSULIN
Ceri Jones
Diabetes Nurse Facilitator
2013

2. Who could benefit from insulin therapy?
People with Type 1 diabetes are dependent on insulin
People with Type 2 diabetes
who have inadequate blood glucose control on optimised oral hypoglycaemic agents (NICE, 2003).
with contraindications to oral hypoglycaemic agents.
who have recurrent symptoms of hyperglycaemia or unexplained weight loss.
who are considering pregnancy.
who are pregnant.
who are post acute MI.
who have acute illness or recurrent infection.
who have foot ulceration and/or infection.

3. generated meal-related
Insulin treatment attempts to mimic the pattern of normal insulin secretion
Short-lived, rapidly
generated meal-related
insulin peaks 70 60 50 40
Insulin (µU/ml)
Low, steady, basal
insulin profile 30 20 10
In healthy adults normal insulin secretion has two key elements: 1. short-lived, rapidly-generated peaks in response to food intake
2. a low level of basal insulin to control glucose between meals.
Insulin treatment attempts to mimic this pattern of normal insulin secretion.
References
Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988;81:442–8.
6:00
10:00
14:00
18:00
22:00
2:00
6:00
Time of day
Polonsky KS et al. J Clin Invest 1988;81:442–8 3

4. Types of insulin Animal insulin (Used since 1922) Short acting
Intermediate acting
Mixture of short and intermediate acting (biphasic)
Human insulin (Since 1982)
Analogue insulin (Since 1996)
Rapid acting
Long acting (basal insulin)
Mixture of rapid and intermediate acting (biphasic)
Several types of insulin are available. All with different time-action profiles to suit different lifestyles and patient needs.

5. What are analogue insulins?
-chain
Analogue (or modern) insulins are formed by modifying human insulin molecules
Like soluble human insulin, analogue insulins are produced by recombinant DNA technology
Gly s s
-chain
Ala
Cys
Phe s s
Thr
Lys s
Pro s
Insulin lispro
-chain
Gly s s
-chain
Ala
Cys
[Slide is animated]
Insulin analogues are modified insulin molecules (they have a different molecular structure to naturally-occurring insulin molecules). The molecules have been modified using recombinant DNA technology to generate properties more suited to exogenous injection (Lindholm, 2002; Heller et al., 2007). This is necessary because subcutaneous injection of human insulin results in a plasma insulin profile that is quite different to that which occurs following the natural release of insulin from the pancreas into the portal vein. Specifically, when injected subcutaneously, the insulin molecules (which are grouped into hexamers) take time to dissociate delaying their action (and also introducing variability; Lindholm, 2002; Heller et al., 2007).
This animated slide shows changes made to the insulin molecule to create insulin lispro and insulin aspart (Hirsch, 2005).
References
Heller S, Kozlovski P, Kurtzhals P. Insulin's 85th anniversary—An enduring medical miracle. Diabetes Res Clin Pract 2007;78(2);149–58.
Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174–83.
Lindholm A. New insulins in the treatment of diabetes mellitus. Best Pract Res Clin Gastroenterol 2002;16:475–92.
Phe s s
Thr
Lys s
Pro
Asp s
Insulin aspart
Hirsch IB. N Engl J Med 2005;352:174–83 5

6. Human insulins Short-acting
Absorbed quickly and last for several hours
e.g., Humulin S®, Insuman® Rapid
Intermediate- and long-acting
More slowly absorbed, last for up to 24 hours
e.g., Insulatard®, Humulin® I, Insuman® Basal
Premixed
Mixture of short- and long-acting insulin (biphasic human insulin) e.g.,Humulin M3, Insuman® Comb
There are many different types of insulin available. Insulins are classified by their onset of action and duration of effect. Short-acting insulin (also known as ‘regular insulin’) is quickly absorbed and lasts for several hours. It is generally injected 20 or 30 minutes before a meal, two- or three-times daily, and its aim is to control increases in glucose following food intake. Intermediate- and long-acting insulin preparations have a slower absorption and a longer duration of action. They are usually injected once or twice daily and can be combined with short-acting insulin. They aim to provide a continuous low level of insulin throughout the day. Premixed human insulin is a combination of a basal insulin (intermediate- or long-acting) with bolus insulin (short-acting) and is usually given twice daily. Because they contain two types of insulin, premixed insulins aim to control glucose after meals and throughout the day and night.
Human insulin used in treatment is made in the laboratory using recombinant technology so that it has the same formula as naturally-occurring human insulin.
References
Diabetes UK provides a complete list of insulins available in the UK: (accessed 2007).
Humulin S and Humulin I are registered trademarks of Eli Lilly and Company Insuman Rapid, Insuman Basal, and Insuman Comb are registered trademarks of Sanofi-Aventis Insulatard and Mixtard 30 are registered trademarks of Novo Nordisk 6

7. ANALOGUE INSULINS Rapid-acting
Absorbed very rapidly, last only a few hours
Aim to control postprandial glucose
e.g., NovoRapid®, Humalog®, Apidra®
Long-acting
More slowly absorbed
Designed to provide a low level of insulin throughout day and night
e.g., Levemir®, Lantus®
Premixed
Mixture of rapid- and intermediate-acting insulin
e.g., NovoMix® 30, Humalog® Mix 25/75
Rapid-acting insulin analogues have the shortest duration of action of all the insulin preparations. They are therefore ideally suited to controlling mealtime glucose. Because rapid-acting insulin is rapidly absorbed, it can be injected with or even after a meal and still be effective. It lasts for only a few hours, when it is needed most.
Long-acting or basal insulin analogues are designed to last throughout the day and night. In contrast to long-acting human insulin preparations, they have been designed to have a relatively peakless action. They are usually injected once daily and can be used in combination with rapid-acting and short-acting insulins as a multiple injection regimen. They can also be combined with oral agents in type 2 diabetes.
Premixed insulin analogues combine a rapid-acting insulin analogue with a longer-lasting version of the insulin analogue leading to an insulin preparation with a biphasic mode of action. Various combinations are available. This type of insulin allows both mealtime insulin needs and insulin needs throughout the day to be covered.
References
Diabetes UK provides a complete list of insulins available in the UK: (accessed 2007).
Humalog is a registered trademark of Eli Lilly and Company Lantus and Apidra are registered trademarks of Sanofi-Aventis NovoRapid, NovoMix and Levemir are registered trademarks of Novo Nordisk 7

8. Insulin Regimens Type of diabetes
There are a variety of insulin regimens tailored to meet the individual needs of people with diabetes.
The goal is to have an insulin release profile most similar to a physiological state.
The treatment option chosen should reflect:
Type of diabetes
Person’s lifestyle, age and ability to self-test blood glucose
Presence of obesity
Choice

9. Types of insulin regimens
Once-daily/twice-daily intermediate- or long-acting (basal) insulin
Once-/twice-/three-times daily premixed insulin
Basal–bolus therapy
Mealtime rapid-acting insulin
In the UK, the two most commonly used insulin regimens for starting insulin therapy in type 2 diabetes are once- or twice-daily intermediate- (or long-acting insulin, i.e., basal insulin) or twice-daily premixed insulin. Both may be used in combination with oral agents continued at their current dose. Other options less commonly used for initiation include basal–bolus therapy or mealtime insulin only in combination with continued oral agents (usually metformin). 9

10. Insulin with or without oral agents?
The majority of insulins are licensed with oral drugs
Metformin should be continued wherever possible
Sulphonylureas can be used with insulin
In February 2007, pioglitazone was indicated for use with insulin in the UK
Sitagliptin is the only gliptin at present that can be used with insulin
Traditionally, oral blood-glucose lowering agents were stopped when insulin was started. However, there are several advantages to combining insulin with oral agents, including a reduced number of injections. Indeed, two of the most popular regimens these days are once-daily basal plus oral agent, and twice-daily premixed plus oral agent. Nowadays, it is recommended that patients continue using metformin when possible; metformin is licensed for use with all insulins. If metformin is contraindicated, the patient may be on a sulphonylurea. In this situation, current NICE guidelines recommend that the sulphonylurea is continued after insulin initiation. Pioglitazone was indicated for use with insulin in 2007, although it is acknowledged that both insulin and pioglitazone are associated with fluid retention, and so combined administration may increase the likelihood of oedema. Patients should therefore be monitored for signs and symptoms of heart failure, weight gain and oedema when using these two treatments concurrently (Actos SPC).
References
Actos SPC. (accessed 2007).
National Institute for Clinical Excellence (NICE). Clinical Guidelines for type 2 diabetes. Management of blood glucose. (accessed 2007)
Pioglitazone now licensed in combination with insulin for type 2 diabetes, (accessed 2007).
Royal College of Nursing. Starting insulin treatment in adults with type 2 diabetes. (accessed 2007).
NICE
Royal College of Nursing. 10

11. Once-daily basal insulin
Exact duration depends on the insulin
Insulin analogues may provide 24-hour cover
Intermediate human insulin preparations may only be active for ~8 hours and have a more pronounced peak activity
basal human insulin
basal analogue insulin
Insulin action
[slide is animated]
Once-daily basal insulin, often used in combination with oral agents, is one of the most commonly prescribed regimens for initiating insulin therapy. Basal insulin preparations provide a low level of insulin over several hours to keep blood glucose under control between meals. Traditional long-acting insulins, such as isophane (NPH) insulin, usually have a peak activity 4–8 hours after injection and can last 13–18 hours (Lindholm 2002). However, the newer insulin analogues, e.g., insulin detemir and insulin glargine, are more slowly absorbed after injection than NPH insulin and may provide sustained insulin coverage (for up to 24 hours) with less of a peak in activity.
References
Lindholm A. New insulins in the treatment of diabetes mellitus. Best Pract Res Clin Gastroenterol 2002;16:475–92.
Insulin injection
Time
Schematic representation 11

12. Benefits of a once-daily basal insulin regimen
Requires only one injection per day
May help overcome resistance to starting insulin injections
Particularly useful when patient’s blood glucose is high overnight and in the morning
Useful for patients who require someone else (e.g., a district nurse) to administer their insulin
May be associated with fewer side effects than other regimens1
Once-daily insulin regimens can be useful when patients are reluctant to start insulin treatment, as only one daily injection is needed. Once-daily regimens are appropriate when blood glucose is high overnight and in the morning, but comes down again during the day.
Basal insulin regimens may be associated with fewer side effects (e.g., hypoglycaemia and weight gain) than other regimens (e.g., 4T study – Holman et al., 2007).
References
Holman RR, Thorne KI, Farmer AJ, Davies MJ, Keenan JF, Paul S, Levy JC; 4-T Study Group. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007;357:1716–30.
Royal College of Nursing. Starting insulin treatment in adults with type 2 diabetes. (accessed 2007).
1. Holman RR et al. N Engl J Med 2007;357:
Royal College of Nursing. 12

13. Premixed insulin – once, twice or three-times daily
Premixed human insulin
Premixed analogue insulin
Premixed injection
Premixed injection
Contains:
Basal component
Short-acting component
Possible regimens:
Once daily with largest daily meal (usually dinner)
Twice daily with dinner and breakfast (figure)
Three-times daily, with each meal
Insulin action
[slide is animated]
Premixed insulins contain both rapid-acting and long- (intermediate-) acting insulin in one preparation. The exact proportions of each insulin within the mixture can vary: a usual mix is 30% rapid-acting insulin and 70% long-acting insulin (e.g., NovoMix® 30) or 25% rapid-acting insulin and 75% long-acting insulin (e.g., Humalog® Mix 25).
Breakfast
Lunch
Dinner
Schematic representation of twice-daily injections 13

14. Benefits of a premixed insulin regimen
Targets mealtime glucose
Suited to people with fairly regular lifestyles, who eat similar amounts at similar times each day
Can be initiated as one injection per day to familiarise patient with injecting*
Second or third injections of same insulin in same device can be added if necessary to optimise control1
Premixed insulin regimens usually involve one or two injections a day, although a third injection can be added if necessary. Because many patients achieve adequate control with only one or two injections a day, premixed insulin regimens may be more acceptable than multiple regimens to some patients. Premixed insulins offer good mealtime control and are associated with a low risk of hypoglycaemia. For people who have a stable lifestyle and regular eating patterns, premixed insulin regimens offer a relatively long-term solution as some mealtime coverage is provided. Premixed insulins can be used in combination with oral agents.
References
Garber AJ, Wahlen J, Wahl T, Bressler P, Braceras R, Allen E, Jain R. Attainment of glycaemic goals in type 2 diabetes with once-, twice- or thrice-daily dosing with biphasic insulin aspart 70/30 (The study). Diabetes Obes Metab 2006;8:58–66.
1. Garber AJ et al. Diabetes Obes Metab 2006;8:58–66 *although most patients are started on twice-daily premixed regimens 14

15. Basal–bolus therapy Breakfast Lunch Dinner Bedtime
Rapid-acting human insulin
Rapid-acting analogue insulin
Long-acting human insulin
Long-acting analogue insulin
Rapid insulin
Rapid insulin
Rapid insulin
Long insulin
Insulin action
[slide is animated]
Basal–bolus therapy involves four/five injections of insulin per day; three* injections of rapid-acting insulin to cover mealtime needs with one or two injections of basal insulin covering insulin requirements between meals. Oral agents are generally discontinued when this regimen is started. In general, the size of the peaks of insulin activity, as shown on the slide, will vary depending on the insulin dose.
Not many patients with type 2 diabetes will be using basal–bolus regimens. They tend only to be used in patients with severe beta-cell failure.
*Note that if people are taking very long-meals (e.g., a Christmas dinner), more than one injection of rapid-acting analogue may be needed to cover the time span of the meal.
Breakfast
Lunch
Dinner
Bedtime
Schematic representation of four injections per day (one long acting, three rapid acting) 15

16. Benefits of a basal–bolus insulin regimen
This regimen produces an insulin profile that is closest to natural insulin production by the body
Offers greater flexibility over type of food and when it can be eaten
Suited to those who are highly motivated
A basal–bolus insulin regimen attempts to recreate the normal physiological insulin profile. Such a regimen offers greater flexibility over what can be eaten and when during the day, because timings of injections can be varied to ensure that there are insulin peaks to cover each meal. Basal–bolus regimens are suited to those who are well motivated in their care to manage the multiple injections required. 16

17. Insulin practicalities
Timing
Soluble insulin: minutes pre-meal
Short-acting insulin analogues: no more than 15 minutes pre-meal and can be given post-meal
Intermediate- or long-acting insulins do not have to be given in relation to a meal
The timing of the shorter-acting insulins in relation to a meal is important in order to maximise the effect of the insulin.
Soluble insulin takes time to be absorbed. Therefore it should be injected 30 minutes before a meal.
Rapid-acting insulin is absorbed quickly so it should be injected no more than 15 minutes before a meal. Ideally, it should be injected immediately prior to the meal.
In some cases, such as when people are unsure of the amount to be eaten – as in young children – the rapid-acting insulin can be injected after the meal. In this way the insulin dose can be adjusted to appropriately cover the amount eaten.
Intermediate- or long-acting insulin can be taken at any time and does not need to be taken in relation to food.

18. Insulin practicalities
Storage
One month in fridge or at room temperature once the vial has been opened
Must never be frozen
Store away from source of heat
If refrigeration not available – Frio bags available
May be damaged by direct sunlight or vigorous shaking
All insulin vials or cartridges have expiry dates printed on them. The expiry date indicates the date before which the unopened vial or cartridge should be used.
Once the vial or cartridge is opened it should be discarded after one month, even if some insulin remains, as the potency of insulin will be lost over time.
The potency of the insulin is also affected by cold and heat. Therefore insulin should not be frozen or stored in direct sunlight or heated areas.

19. Injection Technique
© 2004 BD

20. Injection Technique
© 2004 BD

21. Injection Technique
© 2004 BD

22. Injection Technique
© 2004 BD

23. Injection Technique
© 2004 BD

24. Injection Technique

25. Injection Technique
© 2004 BD

29. Sharps Disposal
Needles from syringes, pen devices and lancets are classified as group B clinical waste.
Sharps bins and safe clips are available on prescription.
Disposal of sharps bin varies depending on local policy.