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Grace,
The Pet diabetes wiki has one case, Molly:
http://petdiabetes.wikia.com/wiki/Case:Miss_Molly
Molly has been using Levemir for over a year and is having good results. I don't see that Molly's person has left any contact information with the case information.
There are a lot of Levemir cases, but the rest are cats, who have a much faster rate of metabolism than either dogs or people. A cat can use NPH as quickly as a person or dog uses R/Neutral. A lot of the cats with wiki cases were switched from Lantus to Levemir with better results for quite a few coming from the Levemir as opposed to the Lantus.
http://petdiabetes.wikia.com/wiki/Ca...:Levemir_cases
Can suggest that you take a copy of the Rand-Fleeman Lente/NPH/PZI/Levemir protocol and go over it with your vet:
http://www.uq.edu.au/ccah/docs/diabetesinfo/link1.pdf
Being able to contact Molly's person would help a lot, I know!
When Molly was Pet of the Month in October 2006, I believe they were at CDMB.
This is an older post where we were talking about Levemir:
Hope some of this might help! 
Kathy
The Pet diabetes wiki has one case, Molly:
http://petdiabetes.wikia.com/wiki/Case:Miss_Molly
Molly has been using Levemir for over a year and is having good results. I don't see that Molly's person has left any contact information with the case information.
There are a lot of Levemir cases, but the rest are cats, who have a much faster rate of metabolism than either dogs or people. A cat can use NPH as quickly as a person or dog uses R/Neutral. A lot of the cats with wiki cases were switched from Lantus to Levemir with better results for quite a few coming from the Levemir as opposed to the Lantus.
http://petdiabetes.wikia.com/wiki/Ca...:Levemir_cases
Can suggest that you take a copy of the Rand-Fleeman Lente/NPH/PZI/Levemir protocol and go over it with your vet:
http://www.uq.edu.au/ccah/docs/diabetesinfo/link1.pdf
Being able to contact Molly's person would help a lot, I know!
When Molly was Pet of the Month in October 2006, I believe they were at CDMB.This is an older post where we were talking about Levemir:
Originally posted by We Hope
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Levemir was around with Novo for quite some time. When it was in the normal formulation other insulins use, 600 nmol/ml, nothing much positive happened with regard to its doing much about controlling blood glucose. Testing people with that formulation was a washout, just as the 1200 nmol/ml formulation of it was.
It was not until Novo increased the formulation to 2400 nmol/ml that Levemir began to show real promise as a marketable insulin.
http://www.emea.europa.eu/humandocs/.../093604en6.pdf
EMEA-Levemir-Scientific Discussion-Page 4
Product development and finished product
"Three formulations of finished product were used in clinical trials. Early clinical trials--Phase I and Phase II--were carried out with formulation A. Formulation B was used in later Phase I and Phase II trials, as well as early Phase II trials. Formulation C was used in late Phase I and Phase III trials and is the formulation intended for marketing.
"The concentration of active substance was increased from 600 nmol/ml (Formulation A--also the concentration of all other insulins) to 1200 nmol/ml (Formulation B) and finally to 2400 nmol/ml (Formulation C) as clinical trials in human subjects with diabetes revealed a higher molar requirement of insulin detemir (generic name for Levemir) compared to human insulin to obtain the same glucose lowering effect."
Page 6
"Contrary to other insulin analogues, insulin detemir was consistently less potent than human insulin in all in-vitro assays. Depending on the assay, the potency was 2-to 10 fold lower. In vivo, it was equipotent in dogs and pigs, 6 fold less potent in rats and > 15 times less potent in mice and rabbits, the species traditionally used to determine the biological potencies of insulins. In clinical studies, the molar potency of insulin detemir was approximately 1/4 that of human insulin, which is within the range observed in vitro. As one unit of human insulin equals 600 nmol, the applicant has defined 1 unit of insulin detemir as 24 nmol or 0.142 mg of the salt-free anhydrous protein (MW=5916.9). The lower potency of insulin detemir relative to human insulin is attributed to the myristic acid moiety being sufficiently close to the receptor recognition site to interfere with insulin receptor binding. As the binding site is not identical across species, the degree of interference may vary across species. Thus, in-vitro binding studies using human, rat, pig, and dog insulin receptors showed that insulin detemir had a relatively lower affinity to human and rat than to dog and pig insulin receptors. Another factor contributing to the observed species differences in potency in vivo is inter-species variations in the binding of insulin detemir to albumin and, consequently, in the volume of distribution and clearance relative to human insulin."
OK--a deep breath to sort out what's been said so far. When you test in vitro, it's not on living beings.
http://en.wikipedia.org/wiki/In_vitro
"In vitro (Latin for within the glass) refers to the technique of performing a given experiment in a controlled environment outside of a living organism; for example in a test tube. Many experiments in cellular biology are conducted outside of organisms or cells; because the test conditions may not correspond to the conditions inside of the organism, this may lead to results that do not correspond to the situation that arises in a living organism. Consequently, such experimental results are often annotated with in vitro, in contradistinction with in vivo."
According to preliminary tests done without involving any animals or people, studies showed that Levemir when formulated at the molar potency of other insulins, was less effective in people and rats than it was in dogs and pigs. They go on to say that it was equipotent (equally potent to human insulin) for dogs and pigs, but much less potent for humans and rats when used in vivo, a living being.
http://en.wikipedia.org/wiki/In_vivo
"In vivo (Latin for within the living) means that which takes place inside an organism. In science, in vivo refers to experimentation done in or on the living tissue of a whole, living organism as opposed to a partial or dead one or a controlled environment. Animal testing and clinical trials are forms of in vivo research."
But there are no details as to which formulation or formulations were equipotent in dogs and pigs when they were injected with it.
Guess we need to talk a little about insulin receptors and so on since they're mentioned here. Insulin receptors are a bit like locks, the "door" won't open when they're in "locked" position. To open the "lock", you need a "key", and it has to be the right key or the lock won't open and the door stays closed. When you have the right key for that lock, you can open the door (insulin receptor binding).
When the insulin you're using won't bind to the insulin receptor (wrong key for the door lock), the insulin cannot be used properly by the body because it can't "gain entrance" to do its job of lowering glucose. It's like having no key, knocking on the door or ringing the bell and whoever's on the other side won't let you in.
Pharmacokinetics--Page 6
"In rodents and subchronic dog studies, females tended to show higher Cmax (Maximum serum concentration (Cmax) ) and AUC (Area Under the Curve) values and exhibited more pronounced accumulation. Similar gender differences were not encountered in humans."
In this, I'd take subchronic to describe a dog who has had some exposure to the insulin on a somewhat regular basis.
Toxicology--pages 7
"Signs of systemic toxicity were limited to effects on plasma glucose, small decreases in serum protein and albumin, urea and magnesium and minor changes in a few organ weights, notable the liver in the rat and the adrenals in the dog. These findings, which were fully reversible, were also made in the NPH human insulin satellite groups and are therefore considered to be exaggerated pharmacodynamic effects."
Would take this to mean that upon ceasing the use of the insulin, the adverse effects reverted to normal. Also note that the preservatives in both Levemir and NPH are the same--phenol and meta cresol.
Levemir is suspended in the bloodstream by binding to albumin. Lantus is suspended by its creation of crystals under the skin after injection. While all other insulins are neutral pH, Lantus is acid pH in the vial. It depends on the reaction between its acid pH and the pH of your skin to create the subcutaneous crystals.
NPH insulin is bound to protamine for its suspension. The first longer-lasting insulin was Protamine Zinc Insulin which contains more protamine than NPH does and that's how it is longer lasting. Hagedorn, the Novo scientist, came up with them both--PZI first and then by reducing the amount of protamine in the formula, came up with the one that bears his name--Neutral Protamine Hagedorn.
Lente insulins are bound to zinc for their suspension; R/Neutral and the rapid-acting insulin analogs Novolog, Humalog and Apidra have no suspension at all.
There have been papers written suggesting that Levemir is no more effective than NPH insulin, that the big difference is the price tag between them. Others say that it's not a "true" once a day insulin like Lantus. What Sanofi-Aventis doesn't tell you is that for many people, Lantus isn't a once, but a twice-daily insulin. r-DNA Ultralente wasn't a once-daily insulin for quite a few people either, even though that's what the claim was.
Both Lantus and Levemir when used with faster-acting bolus insulins, mean that those injections will need to be given in separate syringes. Neither pharmaceutical company has done any work that's been released to the general public regarding combining their long-lasting basal insulin with bolus insulins; the official word as it stands is that combining any insulins with them may change the time action profile of the basal insulin.
Regardless of what insulin you're using right now, you won't see a true test of it until Ali's UTI is gone. You're not using a large amount of NPH at this point, and you could try simple "tweaks" by delaying the insulin shot by 30-45 minutes after food to see if that won't eliminate some of the "drops". Another "fix" for lows when insulin's peaking is to give a small snack shortly before that.
Welcome!
Kathy
It was not until Novo increased the formulation to 2400 nmol/ml that Levemir began to show real promise as a marketable insulin.
http://www.emea.europa.eu/humandocs/.../093604en6.pdf
EMEA-Levemir-Scientific Discussion-Page 4
Product development and finished product
"Three formulations of finished product were used in clinical trials. Early clinical trials--Phase I and Phase II--were carried out with formulation A. Formulation B was used in later Phase I and Phase II trials, as well as early Phase II trials. Formulation C was used in late Phase I and Phase III trials and is the formulation intended for marketing.
"The concentration of active substance was increased from 600 nmol/ml (Formulation A--also the concentration of all other insulins) to 1200 nmol/ml (Formulation B) and finally to 2400 nmol/ml (Formulation C) as clinical trials in human subjects with diabetes revealed a higher molar requirement of insulin detemir (generic name for Levemir) compared to human insulin to obtain the same glucose lowering effect."
Page 6
"Contrary to other insulin analogues, insulin detemir was consistently less potent than human insulin in all in-vitro assays. Depending on the assay, the potency was 2-to 10 fold lower. In vivo, it was equipotent in dogs and pigs, 6 fold less potent in rats and > 15 times less potent in mice and rabbits, the species traditionally used to determine the biological potencies of insulins. In clinical studies, the molar potency of insulin detemir was approximately 1/4 that of human insulin, which is within the range observed in vitro. As one unit of human insulin equals 600 nmol, the applicant has defined 1 unit of insulin detemir as 24 nmol or 0.142 mg of the salt-free anhydrous protein (MW=5916.9). The lower potency of insulin detemir relative to human insulin is attributed to the myristic acid moiety being sufficiently close to the receptor recognition site to interfere with insulin receptor binding. As the binding site is not identical across species, the degree of interference may vary across species. Thus, in-vitro binding studies using human, rat, pig, and dog insulin receptors showed that insulin detemir had a relatively lower affinity to human and rat than to dog and pig insulin receptors. Another factor contributing to the observed species differences in potency in vivo is inter-species variations in the binding of insulin detemir to albumin and, consequently, in the volume of distribution and clearance relative to human insulin."
OK--a deep breath to sort out what's been said so far.
When you test in vitro, it's not on living beings.http://en.wikipedia.org/wiki/In_vitro
"In vitro (Latin for within the glass) refers to the technique of performing a given experiment in a controlled environment outside of a living organism; for example in a test tube. Many experiments in cellular biology are conducted outside of organisms or cells; because the test conditions may not correspond to the conditions inside of the organism, this may lead to results that do not correspond to the situation that arises in a living organism. Consequently, such experimental results are often annotated with in vitro, in contradistinction with in vivo."
According to preliminary tests done without involving any animals or people, studies showed that Levemir when formulated at the molar potency of other insulins, was less effective in people and rats than it was in dogs and pigs. They go on to say that it was equipotent (equally potent to human insulin) for dogs and pigs, but much less potent for humans and rats when used in vivo, a living being.
http://en.wikipedia.org/wiki/In_vivo
"In vivo (Latin for within the living) means that which takes place inside an organism. In science, in vivo refers to experimentation done in or on the living tissue of a whole, living organism as opposed to a partial or dead one or a controlled environment. Animal testing and clinical trials are forms of in vivo research."
But there are no details as to which formulation or formulations were equipotent in dogs and pigs when they were injected with it.
Guess we need to talk a little about insulin receptors and so on since they're mentioned here. Insulin receptors are a bit like locks, the "door" won't open when they're in "locked" position. To open the "lock", you need a "key", and it has to be the right key or the lock won't open and the door stays closed. When you have the right key for that lock, you can open the door (insulin receptor binding).
When the insulin you're using won't bind to the insulin receptor (wrong key for the door lock), the insulin cannot be used properly by the body because it can't "gain entrance" to do its job of lowering glucose. It's like having no key, knocking on the door or ringing the bell and whoever's on the other side won't let you in.
Pharmacokinetics--Page 6
"In rodents and subchronic dog studies, females tended to show higher Cmax (Maximum serum concentration (Cmax) ) and AUC (Area Under the Curve) values and exhibited more pronounced accumulation. Similar gender differences were not encountered in humans."
In this, I'd take subchronic to describe a dog who has had some exposure to the insulin on a somewhat regular basis.
Toxicology--pages 7
"Signs of systemic toxicity were limited to effects on plasma glucose, small decreases in serum protein and albumin, urea and magnesium and minor changes in a few organ weights, notable the liver in the rat and the adrenals in the dog. These findings, which were fully reversible, were also made in the NPH human insulin satellite groups and are therefore considered to be exaggerated pharmacodynamic effects."
Would take this to mean that upon ceasing the use of the insulin, the adverse effects reverted to normal. Also note that the preservatives in both Levemir and NPH are the same--phenol and meta cresol.
Levemir is suspended in the bloodstream by binding to albumin. Lantus is suspended by its creation of crystals under the skin after injection. While all other insulins are neutral pH, Lantus is acid pH in the vial. It depends on the reaction between its acid pH and the pH of your skin to create the subcutaneous crystals.
NPH insulin is bound to protamine for its suspension. The first longer-lasting insulin was Protamine Zinc Insulin which contains more protamine than NPH does and that's how it is longer lasting. Hagedorn, the Novo scientist, came up with them both--PZI first and then by reducing the amount of protamine in the formula, came up with the one that bears his name--Neutral Protamine Hagedorn.
Lente insulins are bound to zinc for their suspension; R/Neutral and the rapid-acting insulin analogs Novolog, Humalog and Apidra have no suspension at all.
There have been papers written suggesting that Levemir is no more effective than NPH insulin, that the big difference is the price tag between them. Others say that it's not a "true" once a day insulin like Lantus. What Sanofi-Aventis doesn't tell you is that for many people, Lantus isn't a once, but a twice-daily insulin. r-DNA Ultralente wasn't a once-daily insulin for quite a few people either, even though that's what the claim was.
Both Lantus and Levemir when used with faster-acting bolus insulins, mean that those injections will need to be given in separate syringes. Neither pharmaceutical company has done any work that's been released to the general public regarding combining their long-lasting basal insulin with bolus insulins; the official word as it stands is that combining any insulins with them may change the time action profile of the basal insulin.
Regardless of what insulin you're using right now, you won't see a true test of it until Ali's UTI is gone. You're not using a large amount of NPH at this point, and you could try simple "tweaks" by delaying the insulin shot by 30-45 minutes after food to see if that won't eliminate some of the "drops".
Another "fix" for lows when insulin's peaking is to give a small snack shortly before that.Welcome!
Kathy
Kathy
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