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            Frequently Asked Questions About Insulin
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     This information was compiled with the help of the
     medical and nursing staff of the New England
     Deaconess Hospital and Joslin Clinic, Boston, MA.

LAST UPDATED: 13May96. Added question 23, a chart showing duration, 
                       peak times, and most likely time for a hypo 
                       for different insulins.                             
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     *** This FAQ is for general information only ***

     Please check with your physician before making any
     changes to your insulin regimen.

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1.   Does the angle of injection make any difference in
     absorption?

     The angle of injection (45 vs 90 degress) makes NO
     difference.

2.   Which causes faster absorption - intramuscular
     injection or subcutaneous?

     Intramuscular (IM) injection is faster. However, IM
     injection is NOT for routine use, and it has its risks.
     It's definitely not for the uninitiated. It's possible
     only if you are not very fat in the area, and most
     likely to go right in the shoulder (deltoid) area. You
     also need a longer needle to reach the muscle,
     although thin persons can get to the muscle easily
     with the regular subcutaneous (SC) needle. There is
     no intrinsic danger in IM injections versus SC
     injections.Imagine, we do it all the time with many
     medications. What happens is that we teach a
     technique, and whenever you start making changes,
     that's when you get into trouble. Also, because the
     absorption after IM injections is faster, it may upset
     your control. It adds another variable to the many
     that can change your BGs every day.

3.   Does slowly injecting insulin affect absorption?

     No, velocity does not make any difference.

4.   How does the injection site affect absorption?

     The abdomen is the fastest. Then comes arms, finally
     the thighs. Buttocks are up for grabs (sorry!). There
     are no scientific data on the rate of absorption in the
     buttocks. These differences may be used to prolong or
     speed up the effect of the injected insulin for special
     circumstances, but it's better to keep injecting within
     the same anatomical area all the time.

5.   Does skinfold thickness affect absorption?

     The fatter the area, the slower the absorption.
     Absorption may also be delayed in areas affected by
     lipohypertrophy.

6.   How does exercise affect insulin absorption?

     Exercise of the injection area increases absorption of
     the insulin in that area. If you exercise the area that
     was injected, the muscles underneath squeeze the
     insulin faster.

7.   Are there any special techniques for increasing
     absorption?

     Local massage can increase the speed of absorption.

8.   What is the effect of ambient temperature on
     absorption?

     Heat increases absorption, cold decreases it.

9.   Does being a smoker change absorption?

     Smoking decreases absorption.

10.  During ketosis, should a person expect any changes
     in absorption?

     Ketosis tends to increase the absorption, which is
     great because it speeds up the effect of Regular when
     you need to lower your BG in a hurry.

11.  Do absorption rates vary from one person to another?

     Yes. Some people with diabetes get 16-20 hours out
     of an NPH/Lente shot, while others get 8-10 hours.
     Day to day variation up to 50 percent may occur in the
     same person, with the same dose, in the same area of
     injection and the same insulin. The same person, using
     the same technique, may see a 25-50 percent difference
     in the time of peak action of any insulin on a day to
     day basis. These are terrible facts - it's amazing that
     we all do so well!

12.  What about the effects of altitude on absorption?

     There are no data on this.

13.  Does the size of the insulin dose have anything to do
     with absorption?

     With large amounts of insulin (over 100 units at a
     time), Regular starts getting more and more
     prolonged. The same thing happens with highly
     concentrated insulins, such as U-500. Regular U-500
     lasts as long as NPH or Lente. Two injections of 10
     units of R each are absorbed faster than one injection
     of 20 units. There is more surface to absorb when you
     inject in two sites. The difference in concentration is
     not apparent with differences of 5-10 units. You have
     to inject a very large amount (around 100 units) to
     really see the difference.

14.  How long before a meal should insulin be injected?

     In general, it is recommended that you inject 30
     minutes before meals. It is impressive to see how
     *MUCH BETTER* the same amount of insulin works when you
     give it 30 minutes before a meal than if you give it
     just before the meal! No matter how you slice it and
     dislike it, DM is a disease that calls for routines.
     The better you stick to them, the better you do. One
     hour for insulin to start, even within a pregnancy, is
     possible but very unusual. Most persons will have a hypo
     reaction before they start to eat. If you wait for the
     BG to drop before eating, you are assured that by the
     time the food is getting into the bloodstream, the
     insulin effect is already there, and the glycemic
     excursion after a meal will be minimal. But, you are
     taking too many chances. What everybody should understand
     is that the longer you wait, the more insulin is already
     functioning and, therefore, the lower the BGs will be
     after a meal.

     It's better to anticipate a glycemic excursion and
     treat it before it occurs, increasing the amount of
     Regular, than try to treat it "retroactively" once the
     BG has already gone up. It takes less insulin to bring
     the BG down when you use it before the big meal.

     If you are interested in finding out when your insulin
     begins to work, you might want to try giving a dose of
     Regular and then checking BG's every 10 minutes to see
     when the BG starts going down. This is somewhat dangerous
     and should be done only with certain precautions. DO NOT
     do this if you are alone or if you do not know a lot about
     your DM.

15.  What happens to the insulin after it is injected?  Why
     can't it all be used?

     Under normal circumstances, some of the injected
     insulin is destroyed (degraded) by enzymes that are
     present in the subcutaneous tissue. In most people,
     it is only a small percentage of the total dose, so it
     doesn't make much difference. Some very unusual people,
     however, have a tremendous degree of subcutaneous insulin
     degradation. They require very large amounts of insulin
     subcutaneously (over 200 U a day), but when you give them
     insulin intravenously they go down to require only 30 or
     40 U a day. I've seen only one of these people in my life.
     You can inject insulin with an enzyme inhibitor called
     Trasylol, but it's expensive, and it's simpler and
     cheaper to give the extra insulin.

16.  Is there any difference in the effectiveness of human
     versus animal insulin?

     Human insulins are shorter acting than animal insulins of
     the same type.

17. Why do blood sugars vary from day to day?

     Each day is metabolically different. This is a very
     catchy phrase to emphasize that there are many varients
     and to explain why some days BG's may go up or down without
     a good explanation. It's best to wait 3 days before making
     changes in insulin doses just to make sure that it's a
     permanent change and not just a fluke of one day.

18.  Why is rolling a vial of insulin preferable to
     shaking the vial before drawing up the insulin?

     The recommendation is to roll only NPH and Lente;
     there is no need to do it with Regular. Do not shake
     them because they tend to make bubbles and then when
     you draw the insulin it comes out with lots of air.

19.  How should insulin be stored?

     Insulin vials should be kept in the refrigerator until
     you start using them. Then, you can keep them in a cool
     place (bathroom), avoiding extreme temperatures. In
     this way, they may be used until they are finished.

20.  Can insulin regimens be flexible?

     Some people use sliding scales and algorithms for the
     regular dose, increasing and decreasing the dose
     according to the amount of food eaten at the time.
     This should not be attempted without a thorough
     working knowledge of your diabetes.

21.  What is buffered insulin?

     Buffered Regular insulin is used in pumps. It acts like other
     Regular insulins. The buffering supposedly makes it more stable
     for use in pumps. Pumps hold large amounts of insulin (mine holds
     315 units) that can't be temperature-controlled. Since most people
     wear the pump next to their body, the insulin can be warmer than
     room temperature. (The insulin in my pump also gets heated in the
     shower.) It's also possible that prolonged contact with plastic
     may degrade insulin. Pump tubing is designed to minimize this, but
     the buffering is supposed to help. Despite all of this, some
     people don't use buffered insulin in their pumps. I'm not sure
     that it really makes a difference, but pump manufacturers
     recommend using buffered insulin in pumps. One brand of buffered
     Regular is called Velosulin.

22.  Does injecting insulin cause tissue growth (lumps)?

     Local injections of insulin may cause lipoatrophy or
     lipohypertrophy.

     With the purifications of insulin and the use of human insulin,
     these local complications are very rare nowadays, except among
     children. For instance, I have not seen them very often among my
     adult patients, but when I go to the Camp every other kid has some
     lumps in the fat of their arms.

     I don't know why this is the case but let me venture some (wild)
     possibilities: a) Kids have subcutaneous tissues that are more
     likely to grow; b) Kids don't like to inject in the abdomen, and
     they tend to inject almost exclusively in the arms, which is where
     they develop lipohypertrophy more often; c) Kids don't rotate as
     often, and injecting repeatedly in the same place will tend to
     cause it more often.

     Remember that the "lumps" tend to hurt less and it's easy to inject
     on them, so kids keep doing it in the same place. Unfortunately,
     insulin absorption from these "lumps" tends to be erratic, and it
     is NOT recommended.

23.  What are the duration and peak times for different insulins?

     Insulin       Start     Peak      End     Lows most likely at

     Lispro        10 min    1.5 hr    4 hr    2-4 hr
     Regular       20 min    3-4 hr    8 hr    3-7 hr
     NPH           1.5 hr    4-10 hr   22 hr   6-13 hr
     Lente         2.5 hr    6-12 hr   24 hr   7-14 hr
     Ultralente      4 hr    10-18 hr  36 hr   10-22 hr

     (This chart is from _Stop the Rollercoaster_ by Walsh & Roberts.)

24.  How are human insulins produced? What are insulin duration times?

     Not all "human" insulins are produced the same way, and the 
     abbreviations contained below explain what method was used in 
     production:

     pyr = purified yeast recombinant
     emp = modified pork
     pbr = purified bacterial recombinant
     mixes = *

     *Human Actraphane (pyr) - This is a premix of 70% NPH (Normal 
      protamine (zinc) Hagedorn) and 30% Regular. Duration is listed as 
      approx. 24 hours.

      Human Actrapid (pyr) - 100% Regular insulin, the only clear 
      insulin. Duration is shown as approx. 8 hours.

     *Human Initard 50/50 (emp) - 50% NPH, 50% Regular. Duration approx. 
      24 hours.

      Human Insulatard (emp) - NPH Normal Protamine (zinc) Hagedorn. NPH 
      insulins use the protaphane or protamine polypeptide to delay the 
      insulin activity instead of zinc (though some zinc is used). This 
      type of insulin was developed to allow mixing insulins without the 
      problems associated with mixing the zinc insulins with Regular. 
      The Protamine slows the absorption of the insulin giving the 
      familiar NPH activity curve but does not combine with the R when
      mixed, leaving the R its fast acting curve. Duration approx. 24 
      hours.

     *Human Mixtard (emp) - same as Actrapane 70% NPH, 30% Regular but 
      reworked pork instead of rDNA modified yeast or bacteria approach. 
      Duration approx. 24 hours.

      Human Monotard (pyr) - 100% Lente - Lente is the older 
      intermediate insulin using zinc to slow the insulin absorption. 
      The free zinc will bind Regular insulin and cause a mixed activity 
      curve if L is mixed with R. Duration approx. 24 hours.

      Human Protophane (pyr) - 100% NPH - identical to Insulatard save 
      that it is produced from yeast cells instead of pork pancreas 
      digest modified to human insulin. Duration approx. 24 hours.

      Human Ultratard (pyr) - 100% Ultralente - Slowest duration 
      available human insulin about 24 hours (pork or beef lasts about 
      36 hours). This is a zinc companion to the "Monotard" but a good 
      bit slower and more "basal" -  should generally NOT be mixed with 
      R. Duration approx. 28 hours.

      Human Velosulin (emp) - 100% Regular - Same as Actrapid save for 
      the source. Duration approx. 8 hours.

      Humulin I (prb) - 100% NPH - Same as Actraphane and Protophane 
      save for source. Duration approx. 18-24 hours.

      Humulin Lente (prb) - 100% Lente (70% Ultralente mixed with 30% R to 
      create a Lente activity curve) - Same as Monotard save for source. 
      Duration approx. 24 hours.

      Humulin M1, M2, M3 & M4 (prb) - Mixes of NPH and R - M1 = 10% R, 
      M2 = 20% R, M3 = 30% R, and M4 = 40% R with the balance of each 
      being NPH. Duration approx. 14-15 hours.

      Humulin S (prb) - 100% R - Duration approx. 5-7 hours.

      Humulin Zn (prb) - 100% UL - Duration approx. 20-24 hours (what 
      used to be the curve for animal Lentes)

      Hypurin Isophane (beef) - 100% NPH - Isophane is the keyword here, 
      it is the "isophane" balance of the zinc that allows NPH to be 
      mixed with R where true protamine zinc (PZI insulins, the oldest 
      long-acting) suffers the same problem as the Lente and Ultralente 
      when mixed with R. Duration approx. 18-24 hours.

      Hypurin Lente (beef) - 100% Lente - Duration up to 30 hours.

      Hypurin Protamine Zinc (beef) - 100% Ultralente - Duration approx. 
      24-36 hours.

     *Initard 50/50 (pork) - 50% NPH 50% R - Duration approx. 24 hours.

      Insulatard (pork) - 100% NPH - Duration approx. 24 hours.

      Lentard (beef & pork mix) - 100% Lente - Duration approx. 24 hours.

     *Mixtard (pork) - 30% R 70% NPH - Same as Human mixtard - Duration 
      approx. 24 hours.

     *Penmix (pyr) - Various mixtures of R & NPH 10%,20%,30%,40% and 50% 
      R - Duration approx. 24 hours.

      Pur-In Isophane (emp) - 100% NPH - Duration approx. 11-24 hours.

      Pur-In Mix (emp) - 15% R 85% NPH - Duration approx. 11-20 hours.

      Pur-In Mix 25/75 (emp) - 25% R 75% NPH - Duration approx. 12-18 
      hours.

      Pur-In Mix 50/50 (emp) - 50% R 50% NPH - Duration approx. 10-16 
      hours.

      Pur-In Neutral (emp) - 100% R - Duration approx. 5-8 hours.

     *Rapitard (beef & pork) - ?%R ?% NPH - Duration approx. 22 hours.

      Semitard (pork) - 100% Semi-lente - Duration approx. 16 hours.

      Velosulin (pork) - 100% R - Duration approx. 8 hours.

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