Insulin Devices and Regimens

Almoutaz Alkhier Ahmed (1) Emad Alsharief (2) Ali Alsharief (3) (1) Dr. Almoutaz Alkhier Ahmed, Diabetologist, Waha Medical Specialist center,National Guard Health Affairs, WR, Saudi Arabia (2) Dr. Emad Alsharief, Consultant family medicine, National Guard Health Affairs, WR, Saudi Arabia (3) Dr. Ali Alsharief, Consultant family medicine, Waha Medical Specialist center, National Guard Health Affairs, WR, Saudi Arabia Correspondence: Dr.Almoutaz Alkhier Ahmed, Diabetologist, Waha Medical Specialist center,National Guard Health Affairs, WR, Saudi Arabia Email: khier2@yahoo.com

Abstract Insulin therapy is one of the treatment lines for management of diabetes mellitus. Insulin therapy can be used at different conditions during the life of the diabetic patient although it is the main treatment for patients with type 1 diabetes. Insulin devices are always the issue discussed by the patients as well as insulin regimens. In our review we discuss these two issues in a simple way so junior medical and nursing staff dealing with diabetic patients can understand them well.

SECTION 1: INSULIN DEVICES
The following devices can be used for the delivery of insulin:

1.1 Syringes and needles
1.2 Pens
1.3 Jets
1.4 Inhalers
1.5 Implants
1.6 Pumps

1.1 SYRINGES AND NEEDLES

Patient Information
o Syringes come in many different sizes to match insulin strength and dosage.
o Syringes are designed for single use only, and the intact syringe should be disposed of
immediately.
o Syringes should be stored in a temperate, dry area.
o Short, fine needles are used.

Advantages
- Syringes are
o extremely small and make the injection process as painless as possible.
o Inexpensive.
- Injections are quick.
- Syringes can be used with all available insulins.
- More than one type of insulin can be used in the syringe.

Disadvantages
- Withdrawing insulin from a bottle may not be discreet.
- It's challenging if you don't see well or your fingers are numb, stiff or shaky.
- Insulin analogues cannot be used with this device.

Information for Health professionals
- There is still a role for syringes.
- Errors in dose are frequent with this device.
- The size of the syringe and needle used by patient need to be verified.
- Inadvertent intramuscular injections may cause glucose swings as absorption is faster than by the subcutaneous (SC) route.
- Advise another device if there are problems.

1.2 PENS



Patient Information
o Insulin pens contain cartridges filled with insulin.
o Pens can have replaceable cartridges or pre-filled cartridges that are then disposed of after use.
o Users turn a dial to select the desired dose of insulin and press a plunger on the end to deliver the insulin just under the skin.
o Pens need to be held in place for several seconds after the insulin is delivered to ensure that no insulin leaks out.
o A new needle needs to be attached for each injection.



Advantages
- Pens are:
o convenient, discreet and easy to use.
o useful with low dosages of insulin.
o easy to use for people with impaired vision or limited manual dexterity.
- The needles used help minimize the discomfort of injection.
- Pens may benefit children and people with needle phobia.

Disadvantages
- Pens cost more than syringes and needles.
- Pens may require two injections if more than one type of insulin is used.
- It is not possible to mix different types of insulin in one pen.

Information for Health professionals
o Greater patient acceptance and preference for the pen over the vial/syringe method may support insulin initiation and compliance, particularly in type 2 diabetes.
o Correct training is the key to successful use.

1.3 JETS


Patient Information
o Jets are needle free insulin delivery systems.
o The insulin is injected directly onto the skin.
o The type of insulin can be varied.
o They can be used with single or mixed insulin.
o Jets are compatible with cartridges and vials.
o Injection sites are the same as with pens.

Advantages
- Jets are
o good for people who have needle phobia.
o flexible and easy to carry around.
o easy to use.
- No needles mean no sharps and no problems with sharps disposal.

Disadvantages
- Bruising is a problem with jets and injections site have to be changed often.
- Jets make a noise when delivering the insulin.
- Jets may be expensive.
- Setting up jets takes time.
- Insulin vials need to be carried around and refrigerated.
- Sterilisation is advised every 2 weeks.
- Disposables may be hard to find.

Information for Health professionals
o Jets are good devices for people who are needle phobic.
o Key disadvantages are bruising and noise which may have an impact socially.
o Injection sites need to be changed often.
o Cost may be a problem.
o Jets give more flexibility and choice of insulin.

1.4 INSULIN INHALER
Inhaled insulin has been withdrawn from the market.

1.5 IMPLANTABLE INSULIN - MINIMED
Patient Information
o Implantable insulin delivers insulin through the peritoneum.
o Implantable insulin has a positive displacement piston design which has an insulin reservoir under negative pressure.
o An external electronic communicator controls operation.
o A side port allows direct access to the delivery cannula for clearing occlusions.

Advantages
-Invisible pump
-Comfortable
-Freedom from injections

Information for Health professionals
- Delivery into the peritoneal cavity with rapid absorption
- COMPLICATIONS:
o Under-delivery caused by aggregation of insulin in the pump or catheter blockage due to fibrin clots.
o Dramatic increase in insulin antibody levels.

1.6 INSULIN PUMPS

Patient Information
o Pumps are devices that are connected to the skin and continuously deliver programmed amounts of insulin into the body
o The basal bolus is the rate delivered during the day.
o The meal bolus is the units of insulin given with meals.

Advantages
- Pumps can be used in patients who are not achieving control with many injections of insulin.
- Pumps can reduce incidences of severe hypoglycemia.
- Pump rates are adjustable for individual activity/meals.

Disadvantages
- Infections may occur at the site of insertion into the skin.
- Should the pump stop working Diabetic Ketoacidosis (DKA) may occur.
- Pumps may be cumbersome with sport and need to be removed is swimming or diving.

Information for Health professionals
o Pumps are the most physiologic method of delivering insulin subcutaneously to achieve near normal glycemic control.
o Pumps give better glycemic control than treatment with multiple daily injections and pumps are well tolerated (2).

Caution
o There is a need for regular glucose monitoring.
o There is a risk of DKA with pump failure.
o Possible infection may occur and pumps need to be removed if sport involves immersion in water.

SECTION 2: INSULIN TYPES AND REGIMENS

2.1 INSULIN TYPES

The appropriate insulin regimen for each patient with diabetes will depend on their type of diabetes and their individual needs and circumstances.
Insulin regimens should be tailored to the individual, taking into account the patient's type of diabetes, previous control, age, dexterity, eyesight, personal and cultural preferences.

Insulin is available in different formulations that act at different rates.
Rapid-acting: insulin lispro, insulin aspart, and insulin glulisine
o Short-acting: regular (soluble) insulin
o Intermediate-acting: NPH (isophane) insulin
o Long-acting: insulin glargine and insulin detemir

Currently Available Insulin Preparations :


Biphasic insulins are also available. These are a mix of rapid- or short-acting insulin with intermediate acting insulins, mixed in different proportions.

2.2 INSULIN REGIMENS
2.2.1 ONCE DAILY REGIMEN:
In the once daily regime, long or intermediate acting insulin is given at bedtime.
o Intermediate acting Insulin -Protophane (NPH) Human Insulin
o Long Acting insulin - Glargine and Detemir

Patient Information
o This regimen is used in type 2 diabetics usually as add on to oral therapy.
o Long acting insulin should be administered every day at the same time.
o Testing blood glucose at home is essential in order to achieve optimal glycemic control and to assist with dose titration.

Advantages
- safety and efficacy has been proven in both intermediate and long acting insulin.
- a once daily regime offers a reduction in overall and nocturnal hypoglycemic events compared to NPH.

Disadvantages
- there is an increased risk of hypoglycemia.
- basal insulin does not cover glucose peaks which occur after meals and in some patients this can lead to hyperglycemia.
- there is no data for safety in pregnancy or in children younger than six years.

Contraindications
- hypersensitivity to any of the products
- Patients may experience a burning sensation with Lantus at the injection site because of the acidity of the insulin.

Information for Health professionals
o Once daily regimes are only for type 2 patients.
o Long acting insulin should be administered every day preferably at the same time.
o Patients on Levemir and Lantus do not necessarily have to snack before they go to bed unless blood glucose levels are low. With Protophane, however, patients should snack as Protophane has a peaking effect.
o If patients do not reach targets, further investigation should be done on the following;
- Suboptimal optimal dose (titration necessary)
- Non compliance with regime
- Poor diet
- Need post prandial glucose coverage (adding a short acting insulin).

2.2.2 TWICE-DAILY REGIMEN:
Biphasic insulin is used.

Patient Information
o Biphasic insulins are injected twice a day (pre-breakfast and pre-evening meal) and assume that the patient eats three meals per day.
o Additional snacks are often required between meals to avoid hypoglycemia.

Information for Health professionals
o It may be difficult to achieve optimal glycemic control.
o Hypoglycemic episodes may occur during the night followed by a fasting hyperglycemia in the morning.
o The peak action varies directly with the proportion of soluble insulin in the combination.

2.2.3 BASAL BOLUS REGIMEN:

Patient Information
In people without diabetes the pancreas constantly secretes a "basal" amount of insulin. This supply is increased shortly after mealtimes to cope with the increase in blood sugar. The aim of the insulin regime is to mimic the normal production of insulin as much as possible.

o A person with diabetes can imitate the above pattern by injecting short/rapid-acting insulin at mealtimes and longer-acting insulin before bedtime.
o This kind of insulin regime is also known as intensified or basal bolus.

Advantages
o It helps maintain a blood sugar level close to that seen in people without diabetes.

Disadvantage
o The use of 4 daily injections.

Information for Health professionals
The graph below shows how a four times daily insulin combination works:

o Also referred to as Flexible insulin therapy, Intensive insulin therapy or Multiple daily injections (MDI).
o Similar results with BD dosing in some patients.
o Post-prandial (2 hours) glucose may be required to assist with dosage adjustment.

Advantages
o Patients learn carbohydrate counting (DAFNE principles - Dose Adjusting for Normal Eating) in order to adjust their short acting insulin dose accordingly.
o Improved flexibility, especially in coordinating insulin doses with meal size and physical exercise.
o Particularly useful for younger patients and those on shift work.
o Does not increase the risk of hypoglycemic attacks.

Disadvantages
o Number of daily injections.
o Insulin pens are generally easier to carry but are more expensive than vials and syringes.
o This regime requires greater amounts of education and effort to achieve the goals, and it substantially increases the daily cost of diabetes care.

2.2.4 CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII OR INSULIN PUMP THERAPY)

Patient Information
Insulin pump therapy is an option for people with type 1 diabetes.

Advantages
o Pumps can be pre-programmed, for example, to compensate for nocturnal and early morning glucose fluctuations.
o The rate of insulin absorption from pumps is more predictable than with multiple subcutaneous injections.

Disadvantages
o Pump therapy is not indicated for everyone with Type 1 DM.
o Specialist training is required.
o The patient must be very motivated to make pump therapy work.
o A trained, specialist team must be available.
o Pump therapy is expensive.

Information for Health professionals
o Pump therapy is particularly useful for patients with recurrent hypoglycemia, unpredictable lives, delayed meals, or pre-breakfast hyperglycemia.
o The insulin used in pumps may be soluble or a fast-acting analogue.
o An adjustable basal infusion rate of insulin is given via an indwelling catheter, supplied from a syringe reservoir worn underneath the patient's clothing. The patient can then activate pre-meal boluses. Pumps can be disconnected for short periods (up to 1 hour) for activities such as swimming.

REFERENCES
Syringes and needles
o www.fda.gov
o www.mayoclinic.com
o Dunning T. Insulin delivery devices. Aust Prescr 2002;25:136-138
Pens
o Asakurq T. et al. Patient acceptance and issues of education of two durable insulin pen devices. Diabetes Technol Ther 2008; 10:299-304
o Dunning T. Insulin delivery devices. Aust Prescr 200 ;25:13613-8
o Korytkozski M. et al. A multicenter, randomized, open-label, comparative, two-period crossover trial of preference, efficacy, and safety profiles of a prefilled, disposable pen and conventional vial/syringe for insulin injection in patients with type 1 or 2 diabetes mellitus. Clin Ther2003;25:2836-2348
o Stockl K et al. An evaluation of patient preference for an alternative insulin delivery system compared to standard vial and syringe. Curr Med Res Opin. 2007;23:133-146
o Graff MR et al. Assessment by patients with diabetes mellitus of two insulin pen delivery systems versus a vial and syringe. Clin Ther 1998;20:486-496
o Thurman JE. Insulin pen injection devices for management of patients with type 2 diabetes: considerations based on an endocrinologist's practical experience in the United States. Endocr Pract 2007;13:672-678
Jets
o www.insulinjet.com
o www.tmh-drugdelivery.com
Insulin Pumps
o Pickup JC, Keen H, Parsons JA, et al. Continuous Subcutaneous Insulin Infusion: an approach to achieving normoglycaemia.BMJ.1978; 1:204 - 207
o Diabetes Control and Complications Trial Research Group. Implementation of treatment protocols in the diabetes control and complications trial. Diabetes Care.1995; 18:361-376
Insulin regimens
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o NICE Clinical guideline; #CG15;Type 1 diabetes in children, young people and adults. July 2004.
o www.endotext.org/Diabetes/diabetes20/ch01s06.html
o www.bnf.org
o Jack L. Leahy, William T. Cefal, "Insulin Therapy" Informa Health Care, 2002, page 21 - 23, www.books.google.co.uk
o US food and drug administration, issued Jan. 27, 2006
o The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986
o Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyosyi S, Kojima Y, Furuyoshi N, Shichiri M: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-117
o UK Prospective Diabetes Study Group: Intensive blood-glucose control with insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853
o Diabetes (type 1) - insulin pump therapy, NICE Technology appraisal (2003)
o Pickup J, Keen H; Continuous subcutaneous insulin infusion in type 1 diabetes. BMJ 2001; 26;322(7297):1262-1273.