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  #1  
Old 05-11-2011, 01:32 PM
jayjay jayjay is offline
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How does injected insulin work?

I've recently started taking insulin (both fast-acting and long-acting) and while they explained what it does, they really didn't get into the mechanics of how it gets to where it's supposed to go.

This is actually two questions, I guess. The first is, when I inject, I inject at one site, usually on my abdomen. How does that insulin, all of which is at one little point under my skin, get to where it needs to go? It's not intravenous, so it's not traveling by the body's "highways". It's just injected intradermally, into the fat layer underneath. So how does it get to all of my cells to play doorman for that sweet, sweet glucose?

Second question would be, how does the long-acting insulin work differently than the short-acting? Does that little (well, not so little for the long-acting) bolus of insulin sit there and gradually disperse in some way? Or does it immediately disperse just like the short-acting, but "hang around" the cells for longer due to some mechanism?

Thanks!
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Old 05-11-2011, 01:44 PM
Athena Athena is offline
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I'm sure someone who knows more about it that I do will come along soon enough, but my understanding is that you don't need to get it to a vein to get the blood to carry it throughout the body, getting it into the fatty tissue below your skin allows capillary action to do the rest.

Long-acting dispersion differs depending on what you're on.

From Using Insulin:

Quote:
Lantus is dissolved in the insulin bottle at an acid pH of 4. Once injected, it comes out of solution in the neutral pH of the body to form microprecipitates. These microprecipitates cause small amounts of insulin to be steadily released over several hours.

Levemir is a modified insulin molecule to which fatty acids are able to attach. This modified structure allows Detemir to bind to albumin, a common protein found in the blood and fat cells. This results in a slow, steady release.
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Old 05-11-2011, 01:51 PM
Lynn Bodoni Lynn Bodoni is offline
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You actually don't want it going into a vein, because it will work too fast. You're supposed to stick the needle in and pull it back a bit to see if you get blood into the syringe, and if you do, you're supposed to choose another site. I don't know of anyone who actually does this, though.
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Old 05-11-2011, 02:08 PM
WhyNot WhyNot is offline
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We use different kinds of insulin to more closely mimic the blood sugar control of a person without diabetes. Our bodies produce and release some insulin all the time, and more at meals. When your doctor gives you one long acting insulin, that mimics the "all the time" insulin, and the rapid-acting or regular insulin are the "more at meals" insulin. We call the "more at meals" (or at other times when your blood sugar is high) a "bolus". Just means "extra", really.

Insulin is a hormone - a protein - which moves from your fat into your blood through tiny holes in the capillary walls, and then throughout the body, where it leaves through tiny holes in the capillary walls.

In an emergency, a person can be given insulin straight into their vein through an IV, but you run the risk of lowering their blood sugar too much or too fast, causing hypoglycemia. Hypoglycemia can cause Really Bad Things, including coma and seizures, so IV insulin is pretty rare, even in hospitals. By using insulin subcutaneously - into the fat pad under your skin - it releases at a much slower and more gradual rate, and is far easier to control without making you hypoglycemic.

Regular insulin takes about 30 minutes to an hour to get to all your cells, which is why you often inject it before you make your meal. Rapid acting insulin takes only 15 minutes to get to all your cells, which is why you don't inject it until you have food on the table in front of you. If you take it and don't eat, you may become dangerously hypoglycemic.

Long acting insulin takes, on average, 1-3 hours to begin to get to all your cells, so you don't have to worry about timing it to your food. Rather, you take it at the same time every day.

There are three ways in which regular insulin is changed into long acting insulin. All of these are designed to slow down the absorption step.

1. Lente crystalline zinc insulin (Ultralente, NPH or Lente insulines). They add zinc to the insulin. This zinc affects the chemical structure so that the insulin breaks down a bit (into dimers and hexamers - smaller chemical chains) at the site of injection, and that makes it absorb more slowly into your system.

2. Insulin glargine. This is an insulin molecule that, with recombinant DNA technology, has had 2 arganine molecules attached in one spot and one asparagine molecule taken out and replaced with a glycine. So it's not exactly insulin anymore, and we call in an "insulin analogue". It acts like insulin where we want it to, but it's got a more neutral pH. More neutral pH means that it's absorbed out of your injection site more slowly.

3. Insulin detemir (Levemir). This is an insulin molecule that has a fatty acyl chain bonded to it. Again, this changes the molecule, so we can't call it "insulin" anymore; it's another insulin analogue. This fatty acly chain makes it attach itself to the albumin in your body. Albumin is a protein in your blood and on your cells. The insulin detemir attaches to it and then peels away slowly, again slowing the time it takes to get fully absorbed.

Other chemical changes are made to insulin to make rapid acting insulin analogues, like Lispro and Aspart. But since you didn't ask about them, I'm going to skip the chemistry. Suffice it to say that those chemical changes make the insulin analogues absorb more quickly than regular insulin. That makes it good for meal coverage, but not effective for long term glucose control. If you used just rapid acting insulin, your blood glucose level would yo-yo all day, and that's not what we want. That way lies peripheral vascular disease and amputations.

The current standard of practice is to use both a long term and a bolus of regular or rapid acting insulin in the amount they're needed in order to keep the patient's blood glucose as even and close to 100 as possible.

Last edited by WhyNot; 05-11-2011 at 02:10 PM..
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Old 05-11-2011, 02:34 PM
Athena Athena is offline
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Originally Posted by WhyNot View Post
If you used just rapid acting insulin, your blood glucose level would yo-yo all day, and that's not what we want. That way lies peripheral vascular disease and amputations.

The current standard of practice is to use both a long term and a bolus of regular or rapid acting insulin in the amount they're needed in order to keep the patient's blood glucose as even and close to 100 as possible.
That's not 100% correct - you can use rapid acting as basal insulin in place of long-acting. That's what pumps do. It's just that you wouldn't want to do it without a pump, since you probably don't want to give yourself injections every few seconds the way the pumps do it.

Last edited by Athena; 05-11-2011 at 02:34 PM..
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  #6  
Old 05-11-2011, 02:42 PM
WhyNot WhyNot is offline
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Originally Posted by Athena View Post
That's not 100% correct - you can use rapid acting as basal insulin in place of long-acting. That's what pumps do. It's just that you wouldn't want to do it without a pump, since you probably don't want to give yourself injections every few seconds the way the pumps do it.
Yes, of course. I should have been clearer that I meant, "if you injected only rapid acting insulin with a syringe" i.e. without a pump. I don't know enough about pumps to teach about them yet. Thank you for that clarification.

Did the rest seem okay? I'm trying not to use obnoxious medicalese.

Last edited by WhyNot; 05-11-2011 at 02:42 PM..
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  #7  
Old 05-11-2011, 02:49 PM
Athena Athena is offline
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Originally Posted by WhyNot View Post
Did the rest seem okay? I'm trying not to use obnoxious medicalese.
Sounded good to me!

Though this made me laugh:

Quote:
The current standard of practice is to use both a long term and a bolus of regular or rapid acting insulin in the amount they're needed in order to keep the patient's blood glucose as even and close to 100 as possible.
I've been diabetic long enough now that "as even and close to 100" just makes me break out in hysterical giggles. I'm sure others can relate!
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Old 05-11-2011, 02:54 PM
WhyNot WhyNot is offline
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Originally Posted by Athena View Post
I've been diabetic long enough now that "as even and close to 100" just makes me break out in hysterical giggles. I'm sure others can relate!
Oh, I know. If it makes you feel any better, though, more recent research is suggesting that super-tight glycemic control may not actually be as important as we make it out to be right now. That there's not an actual medical benefit, and it might just drive patients to stab us to death with sporks. Of course, they're preliminary studies, so only time will tell. For now though, I've still got to emphasize tight control because it's the most supported by the evidence at this time.

Last edited by WhyNot; 05-11-2011 at 02:54 PM..
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  #9  
Old 05-11-2011, 02:58 PM
kenobi 65 kenobi 65 is offline
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Originally Posted by WhyNot View Post
Did the rest seem okay? I'm trying not to use obnoxious medicalese.
I'm a Type II diabetic, though not (yet, anyway) needing to take insulin. Nonetheless, I found your post to be very interesting and informative, and not difficult to follow in the slightest. Thanks for posting it!
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Old 05-11-2011, 03:02 PM
jayjay jayjay is offline
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Absolutely, WhyNot! Very clear. Thank you and everyone else who answered...it really helped me understand what's going on with all the stuff that's going on, so to speak.
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Old 05-11-2011, 03:05 PM
WhyNot WhyNot is offline
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Yay! Awesome, glad I could help. I admit, I used it as an excuse to review insulins for my upcoming nursing license test.
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Old 05-11-2011, 03:11 PM
jayjay jayjay is offline
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Originally Posted by WhyNot View Post
Yay! Awesome, glad I could help. I admit, I used it as an excuse to review insulins for my upcoming nursing license test.
Well, glad I could help you, then!

I'm not really newly diagnosed, but I have been for a number of years poorly controlled, mostly because I kept trying to keep doing things (diet, exercise, etc) the old way and hoping my oral medication would magically take care of everything (I'm on metformin right now, along with the Lantus and Humalog). My last blood labs convinced me I was playing Russian Roulette with three chambers loaded (pretty much an exact quote from my doc), so I'm currently in the middle of diabetic living classes. This is "management week" (last week was "nutrition week"), and we had a long discussion of the types of insulin that are available, but didn't get into the actual nuts & bolts of what goes on at the cellular-to-molecular level.

ETA: And good luck on the licensing!

Last edited by jayjay; 05-11-2011 at 03:11 PM..
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  #13  
Old 05-11-2011, 03:19 PM
WhyNot WhyNot is offline
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Originally Posted by jayjay View Post
My last blood labs convinced me I was playing Russian Roulette with three chambers loaded (pretty much an exact quote from my doc
I'm glad you've seen the light. It would be really hard to post on the Dope with all your fingers amputated, my dear, and I'd miss you.
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Old 05-11-2011, 03:38 PM
Hirka T'Bawa Hirka T'Bawa is offline
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Did the rest seem okay? I'm trying not to use obnoxious medicalese.
Very good explanation, really nothing for me to add, and you did the explanation using laymen terms. You're going to be a great nurse one day.

However, there is a "slight" nitpick,
Quote:
2. Insulin glargine. This is an insulin molecule that, with recombinant DNA technology, has had 2 arganine molecules attached in one spot and one asparagine molecule taken out and replaced with a glycine. So it's not exactly insulin anymore, and we call in an "insulin analogue". It acts like insulin where we want it to, but it's got a more neutral pH. More neutral pH means that it's absorbed out of your injection site more slowly.
You explained what makes Lantus different correctly, however, the conclusion is wrong. I hate to use that word, "wrong", since it is a good explanation in laymen terms, but since this is GQ, I'm allowed to be nit-picky right?

The change of the amino acids help to stabilize the hexamer configuration, which keeps the lantus molecule from acting on the insulin receptors, until it changes into the monomer form. The actual molecule is still absorbed into circulation, it just doesn't do anything while it is there.

But, the way you explained it is better for a patient who isn't a pharmacist or a chemist

Last edited by Hirka T'Bawa; 05-11-2011 at 03:38 PM..
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Old 05-11-2011, 03:51 PM
Athena Athena is offline
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Originally Posted by jayjay View Post
Well, glad I could help you, then!

I'm not really newly diagnosed, but I have been for a number of years poorly controlled, mostly because I kept trying to keep doing things (diet, exercise, etc) the old way and hoping my oral medication would magically take care of everything (I'm on metformin right now, along with the Lantus and Humalog). My last blood labs convinced me I was playing Russian Roulette with three chambers loaded (pretty much an exact quote from my doc), so I'm currently in the middle of diabetic living classes. This is "management week" (last week was "nutrition week"), and we had a long discussion of the types of insulin that are available, but didn't get into the actual nuts & bolts of what goes on at the cellular-to-molecular level.

ETA: And good luck on the licensing!
Good luck with the Insulin. I've certainly found that for me, at least, it's a great drug. Once you get beyond Metformin for Type 2, it seemed to me that all the others were scary in various ways (Sulfonylureas because they can make you go low, Byetta, Januvia, and others because they haven't been around very long, etc. etc.) Insulin works really well, has been around for a long time, and really has only one potential side effect - make a mistake, you go low. I'd already started on my plot to make the docs give me Insulin when they thought I was Type 2, and once they decided I was Type 1 I was thrilled. Well, as thrilled as one could be, given the circumstances.
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Old 05-11-2011, 04:47 PM
aruvqan aruvqan is offline
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Good luck with the Insulin. I've certainly found that for me, at least, it's a great drug. Once you get beyond Metformin for Type 2, it seemed to me that all the others were scary in various ways (Sulfonylureas because they can make you go low, Byetta, Januvia, and others because they haven't been around very long, etc. etc.) Insulin works really well, has been around for a long time, and really has only one potential side effect - make a mistake, you go low. I'd already started on my plot to make the docs give me Insulin when they thought I was Type 2, and once they decided I was Type 1 I was thrilled. Well, as thrilled as one could be, given the circumstances.
I loved byetta, until it started making me lose foods ... I still have trouble with pork and nausea, though I can eat bacon, maybe 2 strips before the idea of bacon makes me nauseated, breakfast sausage makes me want to hurl still =( I have hope, I can eat beef in all forms, chicken in all forms, eggs again finally.
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Old 05-11-2011, 05:03 PM
WhyNot WhyNot is offline
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Originally Posted by Hirka T'Bawa View Post
You explained what makes Lantus different correctly, however, the conclusion is wrong. I hate to use that word, "wrong", since it is a good explanation in laymen terms, but since this is GQ, I'm allowed to be nit-picky right?

The change of the amino acids help to stabilize the hexamer configuration, which keeps the lantus molecule from acting on the insulin receptors, until it changes into the monomer form. The actual molecule is still absorbed into circulation, it just doesn't do anything while it is there.

But, the way you explained it is better for a patient who isn't a pharmacist or a chemist
Absolutely, pick away at those nits! I will amend my notes, since this wasn't really explained in class well at all. So it does slow the breakdown into the active form of insulin, but it doesn't slow absorption from the injection site? Is that right?
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Old 05-11-2011, 07:52 PM
Mean Mr. Mustard Mean Mr. Mustard is offline
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Did the rest seem okay? I'm trying not to use obnoxious medicalese.
Since we're picking at nits...you mentioned that IV insulin is rarely used, even in hospitals. On my unit I don't think a day goes by where there is at least one diabetic soul getting IV (regular) insulin. Granted, they are relatively sick (DKA), but yeah, IV insulin is not at all uncommon.

Anyway, best of luck to you, WhyNot - you're going to be great at patient education.


mmm
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Old 05-11-2011, 08:08 PM
WhyNot WhyNot is offline
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Originally Posted by Mean Mr. Mustard View Post
Since we're picking at nits...you mentioned that IV insulin is rarely used, even in hospitals. On my unit I don't think a day goes by where there is at least one diabetic soul getting IV (regular) insulin. Granted, they are relatively sick (DKA), but yeah, IV insulin is not at all uncommon.

Anyway, best of luck to you, WhyNot - you're going to be great at patient education.


mmm
Huh. I haven't seen it yet. What unit do you work in? I haven't spent oodles of time in ER or ICU where the DKA patients would likely be, I've been mostly Med-Surg and Cardiac/Telemetry. When I asked the nurses up there, most of them haven't ever hung IV insulin; it's truly "rarely" in comparison to regular insulin, which they hand out like injectible Tic-Tacs. Maybe they move the patients off the regular floor if they need IV insulin because they need closer monitoring?
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Old 05-11-2011, 10:21 PM
horsetech horsetech is offline
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I'm a vetico-in-training, not a medico, but I'll take a stab at the IV vs SQ thing. If a person/animal/vegetable/mineral is well-controlled on an insulin regimen, or if you are creating an insulin regimen for them to go home on, you would want to use the same dose and route they use at home - there's no reason to change, IV insulin isn't going to mimic their normal curves at home, and as noted above it requires tighter regulation. I wouldn't be surprised if anyone who needed IV insulin were in or on the way (ER) to the ICU.

When you want IV insulin is when the situation is changing rapidly, there's a greater need for insulin than normal, and you want the insulin to act very rapidly and go away rapidly if you stop. Also, in situations where peripheral perfusion is lousy, absorption from a SQ site might not be as reliable. In a patient with DKA, you need to bring their glucose down by a lot, fairly rapidly, without overshooting, so having a titratable (or however you spell that) drip allows you to do so safely without waiting for absorption and possibly giving too much. Ditto for patients with severe sepsis, acute liver failure, etc. - they may not even be diabetic normally, and you don't really know how their body is going to react given all of the metabolic fluctuations happening. IV insulin w/dextrose can also be part of treating severe hyperkalemia.

BTW, I'm not familiar with the literature re: long-term control, but my understanding of glycemic control in the critical care setting is that, while some subgroups of patients might benefit, tight glycemic control might even be harmful in some cases and so strict control with a goal of 100 or even 110 is usually contraindicated. Here is a consensus statement from several endocrinology groups.
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Old 05-11-2011, 10:29 PM
WhyNot WhyNot is offline
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I'm a vetico-in-training, not a medico,
Ok, here's a probably silly question: what kind of insulin do they give to diabetic horses? Porcine derived, cow derived or synthetic? Do they also use a mixture of long, short and regular acting insulins? Do they do capillary testing for blood glucose? Where do you "stick" a horse? Is "normal" for a horse around 100? Or, for that matter, do they treat diabetic horses at all, or just put them down?

I know it's veering off topic a little, but I'm curious, and you're here, so...
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Old 05-11-2011, 11:45 PM
horsetech horsetech is offline
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Heh. I might be a little out of my depth here, since I haven't gotten to the actual clinical medicine part of school yet, just normal physio stuff, so my clinical knowledge is patchy and based on before-school experience. Maybe one of the real vets will come along and bail me out here.

Insulin-dependent diabetes is VERY rare in horses. The only horse I have seen on SQ insulin was a miniature horse (already a walking endocrinological disaster by breeding) who had persistent glucose dysregulation after hepatitis/anorexia/hepatic lipidosis. Most of the horses I've seen on IV insulin were septic and/or on parenteral nutrition. Unfortunately, I don't remember what source of (regular) insulin we used.

Dogs and cats are more prone to IDDM than horses. There used to be a porcine zinc product called Vetsulin that was marketed for dogs and cats (I think it's off the market now), but a number of vets on a vet geek board I go to like Lantus/glargine. I have a friend who used to just go to Target and buy Humulin-R for her cat - he weighed 25 lb (he was as wide as he was tall) and got 13 units BID. You have now exhausted my knowledge of types of insulin.

One thing we DO see a lot of in horses is insulin resistance. Some of this is equine metabolic syndrome (hmmm, fat people --> fat horses) and some is due to Cushing's disease, which is fairly common in older horses. In either case, there's a lot of counseling about the same things as in people with insulin resistance - low-carb diet, lose weight, and exercise, plus drugs (pergolide) for Cushing's if present. Some vets also recommend Mg/Cr supplementation for insulin resistance, and in a few cases thyroid supplementation is used to encourage weight loss. Because insulin resistance can lead to crippling laminitis and thereby kill a horse, getting it under control is a pretty big deal.

Sorry for the thread-jack!
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Old 05-11-2011, 11:58 PM
panache45 panache45 is offline
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Originally Posted by aruvqan View Post
I loved byetta, until it started making me lose foods ... I still have trouble with pork and nausea, though I can eat bacon, maybe 2 strips before the idea of bacon makes me nauseated, breakfast sausage makes me want to hurl still =( I have hope, I can eat beef in all forms, chicken in all forms, eggs again finally.
Funny thing about Byetta. I took it briefly a few years ago, and I started gagging at random times throughout the day, beginning with the very first time I took it. But even though I stopped taking it, the gagging has continued to this day. It's very slowly diminishing over time.
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Old 05-12-2011, 04:34 AM
aruvqan aruvqan is offline
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Originally Posted by horsetech View Post

One thing we DO see a lot of in horses is insulin resistance. Some of this is equine metabolic syndrome (hmmm, fat people --> fat horses) and some is due to Cushing's disease, which is fairly common in older horses. In either case, there's a lot of counseling about the same things as in people with insulin resistance - low-carb diet, lose weight, and exercise, plus drugs (pergolide) for Cushing's if present.
How does one low carb a horse? Feed them lots of steak? <semi silly but a serious question>

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Funny thing about Byetta. I took it briefly a few years ago, and I started gagging at random times throughout the day, beginning with the very first time I took it. But even though I stopped taking it, the gagging has continued to this day. It's very slowly diminishing over time.
It took me about 2 years before the thought of a piece of bacon didn't turn my stomach, and about 6 months after that before the smell didnt turn my stomach. About 8 months ago i actually ate a piece of bacon ... the smell of breakfast sausage still turns my stomach. I can manage about 5 bites of ham, and maybe half a porkchop of noncured pigflesh. I really miss pork and not having to wonder if I can eat something once I either order it out to eat, or cook it at home. *sigh*
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Old 05-12-2011, 05:40 AM
horsetech horsetech is offline
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This bacon aversion thing is making me sad.

Aruvqan, since horses can digest cellulose in their hindgut, you basically try to feed them more fibrous stuff and less other carbohydrates. The first step is often reducing a horse's grass intake, particularly during spring and fall when growth and stress increase the sugar content in grass. There are nylon grazing muzzles which leave only a small hole in the bottom through which to munch grass, reducing a horse's intake per hour. Some horses can't tolerate grass at all, so you have to find or build them a smaller paddock in which you have killed all the vegetation and just feed them hay. Different types of hay very in non-structural carbohydrate (NSC) content, and hay harvested later in the season tends to be stemmier and lower in NSC's. You can also get your hay tested for NSC's. Horses that need to lose a lot of weight often get a limited amount of hay, as opposed to free choice (as much as they'll eat), which is the norm for many normal horses when not on grass. Finally, if you need to reduce NSC content even further, you can soak the hay in water for an hour to leach out sugars before feeding it to the horse (and dumping the water). Grain feeding is reduced to little or nothing, and so-called ration balancers, which contain vitamins, minerals, and essential amino acids, are given to fill in the nutritional holes that may be left by the limited ration of hay.

If the horse is skinny - Cushing's horses have fat deposits in unusual places and are often overweight but also can be underweight with muscle wasting - there are ways to put calories back in. Alfalfa hay, which is high in protein, is somewhat controversial in IR but is sometimes lower sugar than regular grass hays. Commercial fat and protein supplements are available to mix with a ration balancer or a small amount of grain, or there are plainer sources of fat like vegetable oils, flax seed, rice bran, etc.
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Old 05-12-2011, 07:16 AM
WhyNot WhyNot is offline
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Sorry for the thread-jack!
Sorry for triggering it! But thanks for answering. I have all sorts of respect for veterinarians - y'all have to learn everything human docs do, only for a lot more species! Good luck with school.
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Old 05-12-2011, 11:06 AM
aruvqan aruvqan is offline
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This bacon aversion thing is making me sad.

Aruvqan, since horses can digest cellulose in their hindgut, you basically try to feed them more fibrous stuff and less other carbohydrates. The first step is often reducing a horse's grass intake, particularly during spring and fall when growth and stress increase the sugar content in grass. There are nylon grazing muzzles which leave only a small hole in the bottom through which to munch grass, reducing a horse's intake per hour. Some horses can't tolerate grass at all, so you have to find or build them a smaller paddock in which you have killed all the vegetation and just feed them hay. Different types of hay very in non-structural carbohydrate (NSC) content, and hay harvested later in the season tends to be stemmier and lower in NSC's. You can also get your hay tested for NSC's. Horses that need to lose a lot of weight often get a limited amount of hay, as opposed to free choice (as much as they'll eat), which is the norm for many normal horses when not on grass. Finally, if you need to reduce NSC content even further, you can soak the hay in water for an hour to leach out sugars before feeding it to the horse (and dumping the water). Grain feeding is reduced to little or nothing, and so-called ration balancers, which contain vitamins, minerals, and essential amino acids, are given to fill in the nutritional holes that may be left by the limited ration of hay.

If the horse is skinny - Cushing's horses have fat deposits in unusual places and are often overweight but also can be underweight with muscle wasting - there are ways to put calories back in. Alfalfa hay, which is high in protein, is somewhat controversial in IR but is sometimes lower sugar than regular grass hays. Commercial fat and protein supplements are available to mix with a ration balancer or a small amount of grain, or there are plainer sources of fat like vegetable oils, flax seed, rice bran, etc.
absolutely fascinating! thanks for the info =)
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  #28  
Old 05-13-2011, 05:59 AM
horsetech horsetech is offline
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I'm always happy to provide useless horse trivia, just say the word.

Last edited by horsetech; 05-13-2011 at 06:00 AM..
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