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Insulin Kinds of insulin, action profiles, use in dogs, where to buy, etc.

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Old 12-28-2008, 12:56 PM
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Default Allergies to NPH

Most of what I've collected here on stiff man syndrome had to be accessed via Google cache. The pages are running very slow for some reason, so when you do get them up, click for the text version only right away and you'll be able to read them.

http://74.125.95.132/search?q=cache:...&hl=en&strip=1

http://74.125.95.132/search?q=cache:...&hl=en&strip=1

http://www.gpnotebook.com/simplepage.cfm?ID=1483407407

More on protamine:

http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Diabetes Research & Clinical Practice May 1991

A case of insulin allergy: the crystalline human insulin may mask its antigenicity.

We report an unusual case of insulin allergy. A 48-year-old man with non-insulin-dependent diabetes mellitus receiving biosynthetic isophane human insulin (Humulin N) developed itchy wheal-and-flare reactions at the sites of injection. When Humulin N was changed to a semi-synthetic crystalline human insulin zinc (Novolin U), the allergic reactions completely disappeared. Evaluation of his serum showed a high level of insulin-specific IgE. Skin testing with all commercially available insulins showed immediate local reactions to all agents tested except for Novolin U. In addition, decrystallized Novolin U prepared by lowering the pH with acetic acid also induced a positive reaction. These observations suggest that the crystallized structure of human insulin may mask its antigenicity for allergic reactions.

http://www.ncbi.nlm.nih.gov/pubmed/6...ubmed_RVDocSum

Diabetologica October 1983

Circulating IgG antibody to protamine in patients treated with protamine-insulins

Sera from patients with different types of protamine-insulin were assayed for IgG antibody to protamine. A high prevalence of circulating antibody was found in patients treated with either bovine isophane insulin (26 out of 28 patients; 26 of whom also had antibodies to insulin), or bovine protamine zinc insulin (27 out of 30 patients; all 30 had antibodies to insulin). In sera from 24 patients treated with highly purified porcine isophane insulin, protamine antibody was detected in nine; circulating insulin-antibody was detected in 12 patients, eight of whom had protamine-antibody; in the 12 patients with no detectable antibody to insulin, antibody to protamine was detected in only one (x2 = 8.7, p less than 0.01). This relationship between insulin and protamine antigenicity is of interest as it suggests that the protamine-insulin complex is itself immunogenic.

http://www.fda.gov/medwatch/SAFETY/2...NovoLog_PI.pdf

Page 8 Novolog

Localized reactions and generalized myalgias have been reported with the use of metacresol as an injectable excipient.

http://www.fda.gov/cder/foi/label/2002/21172s3lbl.pdf

Page 10 Novolog Mix

Reactions may be related to the insulin molecule, other components in the insulin preparation including protamine and cresol, components in skin cleansing agents, or injection technques.

Localized reactions and generalized myalgias have been reported with the use of phenol as an injectable excipient.

The insulin molecule, in this case, is insulin aspart, which is not "plain" human insulin, but an analog of it.


Position #28 in the human insulin B chain is altered--Proline is replaced by aspartic acid. Humalog, or insulin lispro, is made by altering the amino acids found in positions #28 and #29 in the human insulin B chain. Proline, normally found at #28, is replaced by Lysine, normally found at #29. The process then replaces Lysine, found normally at #29 with Lysine--the two are in effect, "swapped".

The mixed forms of these two analog insulins are suspended in the same fashion as NPH and NPH mixed insulins are--with protamine as a suspension and phenol and cresol as the preservatives.

http://www.vetsulin.com/vet/DosingProblems.aspx

"Antibodies may be directed either against the insulin or against other foreign proteins in the preparation."

Protamine is a protein.

My Lucky was doing just about the same thing on the pork NPH. What probably made it easier for us to see was that he was not like this at all until protamine suspended insulin came into the picture.

The first week of human insulin worked well--by the second one, it was like giving him no insulin at all--the immune mediated insulin resistance had started. Giving beef a try to see if the two amino acid differences between bovine and canine insulin would make for a longer-lasting insulin for him was the same as with human insulin. His immune system rejected it and destroyed it as it would an invading bacteria or virus. When we started with pork, it was with the old Lilly Iletin II Lente, which was U 100 Lente insulin--no protamine, phenol or cresol. We knew the insulin itself and this type of suspension and preservatives worked great for him.

The strange thing was that out of all of our dogs, Lucky was the one who seemed to have no allergies--no food allergies and never needed to be treated for any other allergies as all of our others did at some time or another. So we really had no "warning" that something like this might happen.

Kathy

Adding to this--

http://www.provet.co.uk/health/disea...ectiveness.htm

Presentation given by Prof Richard Nelson DVM Diplomate ACVIM at the North American Veterinary Conference 2001.
INSULIN INEFFECTIVENESS IN DIABETICS

"Ineffectiveness of insulin should be considered when poor glycaemic control is present in patients that are given insulin at a dose rate of more than 1.5U/kg body weight twice daily and :

"They are still showing the clinical signs typical of diabetes - weight loss, polydipsia, polyuria, polyphagia, lethargy, poor hair coat, neuropathy
Their blood glucose concentrations exceed 300mg/dl (16.8 mmol/l)
Their blood fructosamine concentrations exceed 500 mmol/l"

This article was our "springboard" to connecting the NPH insulin to Lucky's problems. Though he didn't show weight loss, continued PU/PD, or have high bg's or fructosamine concentrations while on it, we identified with the lethargy, poor hair coat and neuropathy--none of which were present when he was using pork Lente insulin.

We then began the process with Intervet and the FDA to file for permission to import Caninsulin for his personal use, as it was still not approved for use in this country.
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