Insulin
Insulin was first extracted by Banting and Best in 1921.
In the 1970s, porcine insulin became available, which was highly purified with higher efficacy and lower side effects.
In the 1980s, human insulins were extracted by recombinant DNA technology.
In the 1990s, Humalog, the first
insulin analog was approved for use.
Characteristics of Insulin:
Onset- the length of time before insulin reaches the bloodstream and begins lowering the blood glucose.
Peak time – the time during which the insulin is at maximum strength in terms of lowering blood glucose.
Duration – is the length of time
insulin continues to lower blood glucose.
Strength of insulin:
U-100 means it has 100 units of insulin per milliliter of fluid.
Injection sites for Insulin: Stomach, arms, thighs, bums
Note: Patients should be advised to change or switch injection sites. Injecting on the same site may cause build up of lumps making the insulin less effective. The stomach is the quickest site to bring the insulin to the bloodstream while the bum is the slowest.
Types of Insulin according to nature:
1. Insulin Regular Human – These are the regular or short-acting insulin. They are polypeptide hormones structurally identical to human insulin developed through rDNA technology. Administered 15 minutes before a meal or immediately after a meal. They should always be clear and colorless. Discard and do not use if discoloration occurs
Brands:
· Humulin R from Elli Lilly is developed from a special non-disease-producing laboratory strain of Escherichia coli bacteria.
· Novolin R from Novo Nordisk is
developed from Saccharomyces cerevisiae (baker's yeast).
· NPH Insulin –Neutral Protamine Hagedorn or Human Insulin Isophane Suspension. These are intermediate-acting insulin. They are cloudy/ milky suspensions of human insulin with protamine and zinc.
Brand names include Humulin N, Novolin N, Novolin NPH, NPH Iletin II, and isophane insulin.
NPH may be combined with fast acting insulin in the same syringe but they should not be combined until it is time to inject. The proper order of withdrawing should be fast acting insulin first followed by NPH, that is, clear first then cloudy.
Limitations of Regular Insulin:
· Slow onset of action. Inconvenient administration which is 15-30 mins before a meal.
· There is risk of hypoglycemia if meal is delayed.
· Long duration of activity which is 12 hours. Possible late postprandial hypoglycemia.
Limitations of NPH:
· Peak is 5-7 hours which when administered at bedtime can cause nocturnal hypoglycemia.
· Action profile is
dose-dependent.
2. Insulin Analogs
Insulin analogs are produced by genetic engineering, wherein, the amino acid sequence of human insulin is altered to change its pharmacokinetics. They bind to insulin receptors producing the same effect as natural insulin. Insulin analogs are also known as designer insulin or insulin receptor ligands.
Compared to human
insulin, insulin analogs more closely resemble physiologic insulin. The basal
insulin analogs provide superior glycemic control with a lower risk of
hypoglycemia compared to NPH.
Humalog or lispro
Novolog or aspart
Apidra or glulisine
Importance of insulin analogs:
· To overcome the limitations of insulin.
· Convenient
· Reduced hypoglycemia
· Improved glycemic control
Ideal characteristics should of basal insulin:
· mimic normal pancreatic basal insulin secretion
· long-lasting effect
· peakless profile
· Reduced risk of nocturnal hypoglycemia
· Once-daily administration
3. Pre-Mixed Insulin
Pre-mixed insulins are usually prescribed for patients needing a simple treatment plan; for older patients having a regular meal and activity paterns or those just starting insulin therapy. These are a combination of fast-acting and long-acting insulin, no more mixing needed and in one injection.
The combination products begin to work with the shorter acting insulin (5–15 minutes for fast-acting, and 30 minutes for short acting), and remain active for 16 to 24 hours.
Examples are:
· Novolin 70/30 (NPH with Regular)
· Humulin 70/30 (NPH with Regular)
· Humalog 75/25 (NPH with Lispro)
· Humalog 50/50
· Novolog 70/30 (NPH with Aspart)
The first number indicates the percentage of protamine suspension (NPH insulin) and the second number indicates the percentage of the fast acting insulin.
The drawback is that NPH, which had a relatively unpredictable action, is the only long-acting that can be used. And when the doses in the mixture are increased or decreased, the risks of both high and low sugars also increase. Long-acting analogs like Glargine (Lantus) and Detemir (Levemir) can not be used in a pre-mixed insulin preparations because they can not mix with other insulins.
If we are going to classify insulin according to length of action (duration)
Human and Analog
|
Short acting |
Long acting |
|
Regular insulin(Human) |
NPH (Human) |
|
Lispro |
Glargine |
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Aspart |
Detemir |
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Glusine |
Degludec (under study) |
Bolus and Basal Insulin
1. Bolus Insulin (Mealtime) – A desirable characteristic should be predictable with rapid onset and short duration of action. The bolus insulins are only taken at meal times to keep blood glucose levels under control following a meal. They need to act quickly.
· Short acting (human)- regular insulin
· Rapid acting (analog) – aspart, lispro, glulisine
2. Basal Insulin (Background insulin) – The role of basal insulin is to keep blood glucose at consistent levels during periods of fasting. The body steadily releases glucose into the blood when fasting so that cells can continually take glucose for energy.
· Long-acting Human – NPH (neutral protamine Hagedorn) Humulin N, Novolin N, Novolin NPH, NPH Iletin II, and isophane insulin
· Long-acting Analogs- Glargine, Detemir
· Ultra-long acting Analogs- Degludec continues to be active for greater than 24 hours
Ideal characteristics of basal insulin:
· mimic normal pancreatic basal insulin secretion
· long-lasting effect
· peakless profile
· Reduced risk of nocturnal hypoglycemia
· Once-daily administration
3. Pre-mixed insulin
· To cover both mealtime and basal needs
· Human and analog (Humalog 75/25, Humalog 50/50, Novolog 70/30, Human 70/30)
Why is there a need for an insulin analog when improved human insulins exist in the market?
The goal of insulin therapy is to mimic the normal physiologic insulin secretion. Ideally, preparations that provide a bolus insulin requirement should have a rapid onset, rapid peak and short duration of action. While, those that provide basal insulin requirement should have a low basal concentration with a long duration of action. Regular insulin and NPH do not mimic the physiologic insulin secretion. Furthermore, regular insulins form hexamers that can dissociate slowly into monomers delaying absorption. They often result to mismatch between requirement and availability as well as poor glycemic control and late hypoglycemia.
Insulin analogs have their sequence of amino acids altered, so that the pharmacokinetics are changed providing a more adequate control of blood glucose. Therefore, insulin analogs were developed to overcome the limitations of regular insulins. The Ultra-short acting or rapid insulin (Lispro, aspart and Glulisine) can overcome limitations of short acting or regular insulins. While long-acting analogs can overcome the limitations of intermediate acting or NPH insulin.
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Type of Insulin & Brand Names |
Onset |
Peak |
Duration |
Role in Blood Sugar Management |
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Rapid-Acting |
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Humalog or lispro |
15-30 min. |
30-90 min |
3-5 hours |
Rapid-acting insulin covers insulin needs for meals eaten at the same time as the injection. This type of insulin is often used with longer-acting insulin. |
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Novolog or aspart
|
10-20 min. |
40-50 min. |
3-5 hours |
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Apidra or glulisine
|
20-30 min. |
30-90 min. |
1-2½ hours |
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Short-Acting |
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Regular (R) humulin or novolin
|
30 min. -1 hour |
2-5 hours |
5-8 hours |
Short-acting insulin covers insulin needs for meals eaten within 30-60 minutes |
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Velosulin (for use in the insulin pump) |
30 min.-1 hour |
2-3 hours |
2-3 hours |
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Intermediate-Acting |
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NPH (N) |
1-2 hours |
4-12 hours |
18-24 hours |
Intermediate-acting insulin covers insulin needs for about half the day or overnight. This type of insulin is often combined with rapid- or short-acting insulin. |
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Long-Acting |
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Long-acting insulin covers insulin needs for about one full day. This type of insulin is often combined, when needed, with rapid- or short-acting insulin.
|
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Lantus (insulin glargine) |
1-1½ hour |
No peak time; insulin is delivered at a steady level |
20-24 hours. Usually injected once daily, or maybe twice daily if needed. |
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Levemir (insulin detemir) |
1-2 hours |
6-8 hours |
Up to 24 hours. Usually injected twice a day. |
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Pre-Mixed* |
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Humulin 70/30 |
30 min. |
2-4 hours |
14-24 hours |
These products are generally taken two or three times a day before mealtime. |
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Novolin 70/30 |
30 min. |
2-12 hours |
Up to 24 hours |
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Novolog 70/30 |
10-20 min. |
1-4 hours |
Up to 24 hours |
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Humulin 50/50 |
30 min. |
2-5 hours |
18-24 hours |
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Humalog mix 75/25 |
15 min. |
30 min.-2½ hours |
16-20 hours |
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*Premixed insulins are a combination of specific proportions of intermediate-acting and short-acting insulin in one bottle or insulin pen (the numbers following the brand name indicate the percentage of each type of insulin). |
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Insulin Pump
An insulin pump is a medical device that is used for administration of insulin. It is also known as continuous subcutaneous insulin infusion (CSII) therapy. An insulin pump is an alternative to using multiple insulin injections.
Traditionally, the device is composed of:
· The pump with controls, processing module and batteries
· A disposable reservoir for insulin (inside the pump)
· A disposable infusion set, with a cannula for subcutaneous insertion under the skin and a tubing system
An insulin pump allows the replacement of slow-acting insulin for basal needs with a continuous infusion of rapid-acting insulin.The insulin pump delivers a single type of rapid-acting insulin in two ways:
· A bolus dose that is pumped to cover food eaten or to correct a high blood glucose level.
· A basal dose that is pumped continuously at an adjustable basal rate to deliver insulin needed between meals and at night.
The insulin pump does not replace the monitoring of blood glucose level but a better control can be achieved. Pumps can be programmed to deliver small doses of insulin continuously (basal) or a bolus dose before mealtime. The delivery system is almost similar to the body’s normal release of insulin.
Advantages:
· No more multiple insulin injections
· The delivery of insulin is more accurate
· Results to improved A1C values
· The delivery of bolus insulin is easier
· Allows flexible timing of meals
· Reduces episodes of very high and very low blood glucose
· Eliminates unpredictable effects of intermediate or long-acting insulin
Disadvantages:
· Can cause weight gain
· Can cause diabetic ketoacidosis (DKA) if catheter comes out and no insulin delivered for hours
· Can be expensive
· Can be bothersome since you are attached to the pump most of the time
· Can require a hospital stay or maybe a full day in the outpatient center to be trained
Insulin Pump Counseling
A. Getting Started with an Insulin Pump
Once you have talked with your diabetes care team and have become comfortable with all of the options on your insulin pump, you and your team will need to do the following in order to get you started.
1. Determine how much insulin to use in the insulin pump by averaging the total units of insulin you use per day for several days. (You may start with about 20% less if you are switching to rapid-acting insulin.)
2. Divide the total dosage into 40-50% for basal and 50-60% for bolus insulin.
3. Divide the basal portion by 24 to determine a beginning hourly basal rate.
4. Then, adjust the hourly basal rate up or down for patterns of highs and lows, such as more insulin for dawn phenomenon and less for daily activity.
5. Determine a beginning carbohydrate dose (insulin: carb ratio) using the 450 (or 500) rule. Divide by the total units of insulin/day to get the number of grams of carbohydrate covered by one unit of insulin. This dose may be raised or lowered based on your history and how much fast-acting insulin you took in the past.
6. Determine the dose of insulin to correct high blood glucose with the 1800 (or 1500) rule. Divide 1800 by the total units of insulin/day to see how much one unit of insulin lowers your blood glucose. This dose must be evaluated by your health care team. It is often too high for children or for people who have not had diabetes very long.
B. Good Insulin Pump Habits
It may take several months to get comfortable with the pump. During those first months is the time to adopt some good habits. Here are some tips to help you adjust:
· Take your insulin at a specific time, such as five minutes before you eat, so you don't forget boluses
· When traveling anywhere, bring extra supplies or at least an insulin pen, in case you are unable to use your pump for some reason
· With an insulin pump, when you eat, what you eat, and how much you eat is up to you. You can eat more carbohydrate and still manage your blood glucose, but weight gain can happen. Talk to a dietitian about this when you start on the pump. It's a lot easier to not to gain weight, than it is to lose it after you have already gained it
· When you take the insulin pump off or turn it off, figure out a system to remember to turn it back on. Listen to the alarms on the pump or set a timer
· Make a habit of recording blood glucose checks, carbohydrate amounts, carbohydrate doses, correction doses, and exercise when you do them. It really helps to sit down and look over your blood glucose record at the end of every week (or even every day) to see if you have any problem areas. Reviewing your records is the key to improving blood glucose control
· Your diabetes provider and insulin pump company have record forms, or you can make your own. Just be sure that you have enough room to record everything you need. Keeping daily records is best, but some people find keeping records for two weekdays and one weekend day gives enough information to see the pattern
Reference:
2. http://en.wikipedia.org/wiki/Insulin_pump
Benefits of Insulin Pen over Insulin Vials:
1. Injection process is simpler and more convenient, which is, just pushing the button and holding the pen still. No need to draw insulin from the vial and no need for pulling some skin up when injecting.
2. When in public places like restaurants, the pen is more socially acceptable because it looks less a medical device that might scare a few people specially kids.
3. It is easier to train people in dialing the dosage rather than withdrawing insulin from vials.
4. It is said that diabetics using pens have a better adherence compared to vials.
How to inject insulin Pen
Step 1: Prepare the Insulin Pen
· Remove pen cover or cap. If using milky-white insulin (intermediate-acting or NPH), gently roll pen between palms for 15 seconds to mix.
Step 2: Remove the paper tab and needle covers
A. A. Pull the paper tab off the pen needle.
B.B. Screw needle onto the end of insulin pen.
C.C. Remove outer needle cover.
D. D. Remove inner needle cover to expose the needle.
Benefits of Oral Antidiabetic Agents and Insulin Therapy
· Improved glycemic control
· Treats multiple physiologic abnormality
· Reduced potential for weight gain
· Less insulin is needed to achieve good glycemic control
Some clinical criteria to keep in mind:
· Sulfonylurea + Biguanide : reduces hepatic insulin resistance and help minimize weight gain
· Sulfonylurea + Alpha-glucosidase inhibitor : reduce postprandial glucose levels
· Sulfonylurea + TZD : reduce peripheral insulin resistance and insulin requirement
· Reduction of insulin resistance can occur through the use of the biguanide and/or a thiazolidinedione, and a sulfonylurea would maximize endogenous insulin secretion in a more natural pattern than injected insulin
· If
the goal is not met with combination of oral medication, a third agent may be
added or insulin may be started.
· If still, the goal is not met, a full insulin program with 24-hour a day coverage with or without insulin sensitizers.
http://www.medscape.org/viewarticle/418591_11
Step 3: Prime the Insulin Pen
A. A. Prime the pen and clear the air from needle. This adjusts the pen and needle for good accuracy when it's time to measure your insulin dose. Turn the dose selector knob at end of the pen to 1 or 2 units (watch dose markings change with turning of knob).
B. Hold the pen with needle pointing upward. Press dose knob up completely while watching for insulin drop or stream to appear. Repeat, if necessary, until insulin is seen at needle tip. The dial should be back at zero after completing the priming step.
Step 4: Dial in Your Insulin Dose
· Turn dose knob to "dial in" your insulin dose. (You can dial backward, too.) The pen will allow you to receive only the amount that you have set. Double-check the dose window to assure your proper dose.
Step 5 : Choose an Injection Site
· Select an injection site. The abdomen is the preferred place for many types of insulin--between the bottom of the ribs and pubic line, avoiding 3-4 inches surrounding the navel. The top of the thighs and back of upper arms (if you are flexible) may also be used.
Step 6: Inject the Insulin
A. Curl fingers around the upper end of the pen to hold secure. Poise thumb, in air, above dose knob.
B. Gently pinch up skin with your free hand.
C. Quickly insert the needle at a 90-degree angle. Release the pinch.
D. Use your thumb to press down on the dose knob until it stops (the dose window will be back at zero). Leave the needle in place for 5-10 seconds to help prevent insulin from leaking out of the injection spot (see package insert to learn timing recommendation for your pen).
Pull the needle straight out of the skin. It is normal to sometimes see a small drop of blood or bruise. You may lightly pat the site with a tissue or cotton ball, but do not massage the area.
Step 7: Prepare the Insulin Pen for future use
· Place outer needle cover over needle and twist to unscrew needle from pen. Throw used needle away in hard container (an empty pill container or detergent jug are safe examples). Put the outer needle cover back on the pen.
Pictures and steps from:
http://www.diabeticlivingonline.com/medication/insulin/how-to-use-insulin-pen?page=0
Exenatide (Byetta)
Exenatide (Byetta) is an injectable medicine for use of patients with Type 2 diabetes. It can be used with Lantus but should not be used with short- and rapid-acting insulin. It is neither oral pills nor insulin. It is made from a synthetic form of Gila monster saliva and works by mimicking the effects of a human hormone called GLP-1. GLP-1 is normally released after meals, stimulates digestion and insulin production. It also prevents the liver from producing too much sugar. Side effects are weight loss and severe nausea.
Exenatide Extended Release (Bydureon)
Exenatide extended release (brand name Bydureon) is taken as single weekly dose along with diet and exercise to control blood glucose in type 2 diabetes. It helps the pancreas to make insulin while decreasing glucose release from the liver when blood glucose are high. It also slows digestion and keeps individuals feeling full longer and decreases appetite. As with standard exenatide, there is an increased risk of hypoglycemia when used in combination with Sulfonylureas. This medication is not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis, and is not recommended to be used with insulin.
Liraglutide (Victoza)
Liraglutide (brand name Victoza) stimulates insulin production while suppressing the liver‘s glucose output and may cause weight loss. It can initially cause nausea, which may get better or go away with time.
Pramlintide (Symlin)
Pramlintide (brand name Symlin) slows food from moving too quickly through the stomach and helps keep after-meal glucose levels from going too high. It can suppress appetite and may cause weight loss. It also reduces glucose production by the liver. It is taken before meals and may cause nausea. To limit nausea, start with a low dose. Pramlintide cannot be mixed with insulin in the same syringe so it must be taken as a separate injection.
- Sources: http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/insulin/other-injectable-medications.html#sthash.5r65RTaA.dpuf
- Course creator: Lurdes Pastor
- Course creator: Eliana Sequeira
- Course creator: Molly WONG