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**BestBuddy** · 11-23-2008, 12:26 PM

Re: My Ali girl and question about basal insulins

Hi Patty and Ali,
I can't help with the insulins but just wanted to say welcome.
Jenny & Buddy

**k9diabetes** · 11-23-2008, 01:22 PM

Re: My Ali girl and question about basal insulins

Hi Patty,

I'm not aware of any dogs who are using Levemir - I have been very curious to see how they do on it. However, dogs generally do not do well on very long lasting insulins and that may turn out to be the case with Levemir. It's working well in cats as they generally require a long-acting insulin. My impression is that dogs just never get enough of the insulin out to get much effect. But it could be that it would work in combination with a faster acting insulin.

A little background...I have a 9 y/o golden retriever. She was diagnosed with DM in May '08. She is my allergy girl. The end of June, she developed a hematoma on her ear and needed surgery to drain and repair it. Since then, we've been struggling with regulation and getting her allergies under control. My holistic vet recommended a raw diet to 'give her pancreas a break.' She's done well on it but needs to be fed multiple times to carry her through the peak of her insulin. She is on Humulin N 12 hours apart, 8 1/2u at night and 8 3/4u now during the day. She has also had a couple of UTIs we are dealing with. I do home test with a OneTouch UltraSmart meter.

Since you're home testing, you could do a carefully monitored trial of Lantus and see what you get. Betty's Monk does really well on it.

Do you have curves you could post?

Also, could you describe the content of Ali's raw diet?

It could be that the diet could be tweaked to improve the insulin coverage...

I'm assuming it's fairly high protein so it surprises me a little that she's having trouble, from what it sounds, with lows later on.

Anyway, if you could post your curves and the diet, we might be able to help more with ideas on what might or might not help.

Also, if you could list what she's allergic to so we know what can't be used.

Natalie

**Debbie & Apollo** · 11-23-2008, 01:35 PM

Re: My Ali girl and question about basal insulins

Hi Patty and Ali!

just wanted to say welcome!

Sorry we use Vetsulin ---
we have had experience with pancreatitis however

Debbie and Apollo

**Cara's Mom** · 11-23-2008, 02:18 PM

Re: My Ali girl and question about basal insulins

Welcome to the forum Patty and Ali!
I am no help either........use Caninsulin

...just want to say Hi!

Pretty sure you'll get your answers here!!!

**Ricksma** · 11-23-2008, 02:20 PM

Re: My Ali girl and question about basal insulins

Natalie, I don't know if you remember Peggy and her Miss Molly, or Breanne and Kramer from the other board, but I believe they are both on Levemir, and Molly is also on Humalog for her meal bolus. Perhaps she could be of help?

Love and hugs, Teresa and Ricky

PS...I don't post to the other board any more, so I haven't heard from them in a while.

**Patty** · 11-23-2008, 03:12 PM

Re: My Ali girl and question about basal insulins

Thanks for the welcome

I am looking into Lantus or Levemir as a 12 hour insulin, not as the long lasting 24 hour most people think about. Just looking for a flatter profile.

Our curves are not an accurate reflection right now. She's into her 2nd week of Baytril for UTI (e.coli). I am also giving her D-Mannose to help clear it.

She was "stuck" in the 250-400s range for a while, probably due to the UTI. She also has times where her insulin takes hold quickly and she drops like a rock - over 100 points in an hour. I'm wondering if this was also due to the infection. The last 24 hours she's been mostly below threshold - I'm thrilled!! But we are still tweaking things.

She is eating Northwest Naturals Bison http://www.nw-naturals.net/bison.htm It is a 60/40 mix of protein/veggies.
Her current schedule is
5:45a - 25 nuggets/shot
10:15a - 35 nuggets
5:45p - 25 nuggets
9:45p - 35 nuggets

I need to increase her food though. She's still losing some weight and needs to gain. At one point I added 5 extra nuggets to each meal, then increased her insulin the next day to compensate for the extra food but her numbers continued to rise higher into the 400s, so I backed down to where she'd been and let her bgs fall back in place.

Today I added 5 nuggets at 2:15p. We'll see what that does to her bg.
(sorry I know this looks like a mess - the spaces don't show up when I previewed it)

106 - 5:45p 8 � 25 nuggets
138 - 6:15p
177 - 6:50p
97 - 9:45p 35 nuggets
10:30p 1 Baytril
210 - 3:00a
154 - 5:45a
5:55a 8 � 25 nuggets
246 - 8:50a
82 - 10:15a 35 nuggets <-- I'm thinking of feeding this meal earlier
139 - 11:30a
156 - 12:00p
170 - 1:00p
157 - 1:50p
2:15p 5 nuggets
190 - 3:13p

Mostly I feel like I'm feeding her insulin. It's hard to feel comfortable leaving her alone at this point - she's pretty unpredictable yet. This is the best 24 hours we've had in a long time! I monitored her pretty tightly today hoping to try to repeat the pattern tomorrow.

I've tried adding buckwheat to her 2nd meal. She got pretty itchy with it. We've done testing for environmental allergies but not for food. I was told the blood test is not very accurate and we just tried to stay away from common allergens. I was thinking of trying some oatmeal or rice at some point.

Really this is a fact finding mission for me. I don't think I can truly get her regulated or try switching until we know the UTI is gone and not interfering with her bgs. I would love to do a trial with Lantus or Levemir to see how it does. I just wish there was more info out there! It's a bit scary to go it alone. I've heard there used to be a lot more dogs on Lantus that were raw fed but that it's dwindled away.

Any input is always welcome.
Patty

**Debbie & Apollo** · 11-23-2008, 03:59 PM

Re: My Ali girl and question about basal insulins

Just wanted to add -
when Apollo was on any other drugs we had to adjust his insulin and he was hard to regulate.

We especially watch for lows now. Yes we learned the hard way

Debbie and Apollo

**We Hope** · 11-23-2008, 06:00 PM

Re: My Ali girl and question about basal insulins

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

**eyelostit** · 11-23-2008, 06:00 PM

Re: My Ali girl and question about basal insulins

Hi Patty and Ali

Just a welcome to the board, we're all here to help, ask any questions even if you think they sound dumb, we have already asked them

**Patty** · 11-23-2008, 06:38 PM

Re: My Ali girl and question about basal insulins

Thank you all for the welcome!

Kathy, Thank you for the information! You did a lot of work to find all of that! I did know about the difference in potency between dogs/pigs and humans.

I also know Peggy and have talked to her about Molly's use of Levemir. I've been looking for other dogs as well on this insulin. She did say that the potency factor was an issue with both Molly and Kramer. It is about 4x stronger because of the increased concentration.

A few of the differences: Ali is a larger dog, a lot more active and Molly has atypical cushings. I'd like to know how an active dog does on a basal insulin. I know when Ali catches her ball, greets family, or see the UPS man she can drop almost 50 points.

When looking just at Levemir and Lantus: The pros and cons I see...
Lantus I've been told can sting because of the pH factor
Lantus has been used more in dogs than Levemir
Levemir is said to be a more predictable profile than Lantus and more predictable between individuals and their particular metabolism (humans)
Levemir may be harder to find the right dose
Both are expensive!

And you are right, I won't know until the UTI is gone. The 5 nuggets this afternoon put her into the high 200s preshot, then she rises from her meal above that. So I need to keep working on the tweaks. Her pattern changes so easily. We were having duration issues before. Now she is in the low 100s preshot. I may try adding a grain to her 2nd meal to see if that will keep her from going too low late afternoon.

Another question, has anyone here used expeller pressed coconut oil in their diabetic dog? My holistic vet talked to me about this in trying to help Ali gain some weight. I know it needs to be done very slowly. It is one of the 'good' fats that apparently doesn't need insulin to 'unlock the gate' in order to be used by the cells.

Thanks,
Patty

**k9diabetes** · 11-23-2008, 10:55 PM

Re: My Ali girl and question about basal insulins

She gets two injections of NPH, yes?

**k9diabetes** · 11-23-2008, 11:41 PM

Re: My Ali girl and question about basal insulins

Hi Patty,

A few thoughts... (congrats on great numbers, by the way - looks like the UTI is clearing!)

Hmmm... the food has some pretty sugar rich foods as its main vegetable is carrot and fruit is watermelon plus little fiber, which it seems like Ali could use. The lettuce and broccoli aren't going to provide much in the way of glucose when they get digested, which probably occurs later in the cycle.

Northwest Naturals� Bison
INGREDIENTS: Bison heart, Bison liver, carrots, romaine lettuce, watermelon, broccoli, Bison kidney, ground Bison bone, flaxseed, safflower oil, garlic, dried kelp, inulin, salt, potassium chloride, fish oil, parsley, apple cider vinegar, ginger, zinc proteinate, iron proteinate, copper proteinate, manganese proteinate, mixed tocopherols (as preservative), rosemary extract, Vitamin E supplement, Vitamin D3 supplement

Guaranteed Analysis (as fed):

Crude protein10.0% minCrude fat8.0% minCrude fiber1.5% maxMoisture72% maxCalories299 kcal per 8 oz. approximately 40 nuggets or 1/2 of a dinner bar

When Chris was on a higher fiber kibble that had a larger share of carbs, he actually got a boost of glucose from that kibble later in the day - something that would help Ali.

On canned food (chicken as the first ingredient and rice as the only grain) he digested the food a lot faster.

You might try adding a complex carb. Again, it's impossible to say what Ali will do with it. Some process oatmeal very quickly. Others slowly. We originally tried adding kibble to get a boost of blood sugar early and got one late instead.

Once we went to the Canidae/California Natural, we were happy with the diet and so we lived with a postprandial rise as all his numbers were still in a very good range.

In the interim, I agree that you should try giving that in-between meal earlier. You want to get it going in before she bottoms out so that it's turning to glucose when she needs it. From this curve, at least, you're waiting until she's well into a drop already. Giving the additional food sooner should give you better balance and less of a rise late in the 12-hour period.

It can be difficult to aim for tight control AND be able to leave them alone / avoid feeding interim small meals. Ultimately, sometimes... and I'm not saying Ali is there yet... it's just better to run their regulation a little looser. We had the benefit of mostly being home with Chris but definitely on days we couldn't do that we would let his numbers run higher for his safety. There comes a point with some dogs where they just can't be kept at really tight regulation cuz they bounce around, throwing a low day not once a year but once a week or two weeks without any warning.

I'm not sure what Ali's curves looked like on other foods... that may give you some clue to how tweaking the diet would affect things.

Natalie

**k9diabetes** · 11-23-2008, 11:42 PM

Re: My Ali girl and question about basal insulins

Is there scheduled exercise in the curve somewhere? That could make a big difference in the levels.

**Patty** · 11-26-2008, 02:26 PM

Re: My Ali girl and question about basal insulins

Hi Natalie,
Sorry it's taken me so long to get back. A lot going on here.
Some answers:
You're right. She is on 2 injections

I keep a really detailed journal of exercise, food, potty times, etc. It's actually a bit overboard, but I started it when we were having trouble and it's helped me sleuth out some issues. She typically gets some exercise in the way of catch, frisbee, or a walk in the morning and early afternoon before her insulin has worn down. No heavy sprinting with this though. And I try to keep it pretty consistent.

Lately, she's been running high. My husband is home (long story...we've been waiting for housing on a military post and have been apart for a bit) so what with traveling into and out of town to visit family, her schedule's a bit off.

I have been looking into BRAVO's formula for food. They have the option of getting the basic meat, organ meat and ground bone. Then you add the veggies and carb/fiber. I know of another person feeding this food and it's been working really great for them. I just can't get it around here. Once we move I should be able to get it in NY though.

I really hate to go back to kibble. The Wellness reduced fat CORE worked for us for a while but her ears were flaming red on it. I really think it's the grain proteins she doesn't handle well. I will keep tweaking things 'til we get it! But I also know this next month will be a bit rocky as we'll be moving soon.

Thank you for your input. Once she's out of the woods with the UTI and we are settled, I am going to try to regulate with what she's currently on. If that doesn't work then I'm going to try the BRAVO so I can get away from the higher glycemic carrots/watermelon in her food. If I can't get that tweaked, I may consider the Levemir. I really think the raw food is a huge benefit for her allergies and it just seems like it would work better with a flatter profile insulin.

Patty

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Patty's Ali - my precious, beautiful angel

Patty's Ali - my precious, beautiful angel

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