Act Acting » Method Acting » Going from 70/30 to mixing R & NPH

Going from 70/30 to mixing R & NPH

Question:

This is all explained on p. 48-49 of "Galenics of Insulin" by Jens Brange.

I must confess I am totally confused by and unable to follow your arguments. The limitation must be mine. I am reminded of my first encounter with Husserl’s _Cartesian Meditations_. I was able to follow his arguments up until page vi in the introduction where he stopped talking about Descartes. From then on I was totally at sea. I have ordered Brange from the library and will review it as well as the half dozen papers cited in Kahn and Weir and a couple of recent things from medline. As far as I can tell from the abstracts the recent papers agree with current recommendations and practice. If I find any reason to disagree with standard practice, I’ll post. Otherwise we must agree to disagree. Just to be clear, since it is hard to pick things out of several layers of , my position is that current standard recommendations are correct:

Mixing NPH and regular in the syringe for periods of several hours, up to 21 days when refrigerated, prior to injection fine. Even though many patients do it with success, mixing the lente insulins with regular in the syringe before injecting is bad practice and the source of significant absorbtion variability. I realize that you made no claims with respect to the lente insulins. I think it is important in this context to clearly state that the recommended practices for the two types of insulin are different. — Charles Coughran

Response:

—–BEGIN PGP SIGNED MESSAGE—– FINE! What good is my killfile if everybody responds to this blatant foolishness and I therefore see it anyway.! Hrumph. Mickey, poopsie: you’re wrong. Again. While mixing NPH and regular *in the vials* would be a problem, and indeed will cause problems if you pre-mix them accidentally (by injecting the NPH into the regular bottle for example), a *small* dilution of regular into the NPH does not affect it noticeably, which is why you draw the regular first, then the NPH: I am not sure if this is becuase of the very high concentration of zinc and protamine in the NPH, whether it is super-saturated or not. It’s not important. What’s important is that the MI diabetic uses the same or similar mix, consistently, so that even if there is slight mixing affects they are accomodated in their regime. You have also *completely* ignored the time constants: the reaction of insulin with the other NPH ingredients takes significant time, longer than a typical dosage’s effect. I’m not sure it is as much as a day, but it is quite long enough for the combined NPH/insulin doses which I have been taking *for more than 20 years* to provide two *distinct* peaks, which I actually time for snacks, etc., like *the other thousands/millions of people who have successfully used the regime since the invention of NPH, you blithering numbskull*. And you can start that list of people with the several hundred kids/staff I attended and later worked with at diabetic camp, 20 years ago. The reason 10 units of 70/30 is not the same as 3 units regular added to 7 units of NPH is that the results of pre-mixing are different than those of mixing at injection time, that’s all. You persist in reading a single paper on a chemical process and "deducing" medical treatment while ignoring its actual history and the case studies available to you, and which people have mentioned out here. The paper does *not* outweigh reality, even if the paper is on the physical chemistry which is apparently your profession. Expecting people to believe *your* paper, in obvious contradiction to their own medical histories, flies in the face of reason. This is particularly true since you have been shown wrong time and time again on regimes and medications *other* than the long-acting insulin which you use. And you seem to fail to understand time constants, response times, feedback, and reaction rates, in this and everything else: I suspect it is part of why you only manage well with a nearly constant insulin level. That eliminates a factor of dynamic time which the rest of us use, varying meal times and dosages and changes on a daily basis. You replace it with a fixed level against which you balance exercise, meals, etc. It means you juggle with one hand against a wall, while the rest of use two hands. Your method works, if all you want to do is keep one ball in the air. But the rest of us can walk around the Village Green, seeing the shows and joining the crowds there. Your regime works for you, fine, but stop blithering about what you patently do *not* understand. Stick to what you know. You want to be useful? Helpful? Talk about details of balancing dance and the anxieties of performances with blood sugars and eating. Or about what dietary tricks prevent overpowering that peakless insulin you talk about. And *definitely* stay off the subject of women. Nico Garcia My opinions are my own, not MIT’s or my employer’s or my cat’s (Well, maybe my cat’s….) —–BEGIN PGP SIGNATURE—– Version: 2.6.2 iQCVAwUBMSSkoKltw5SaOnTxAQHtUAQAm8nZjdFfdta9YEsNayQHiwulJXQR9b6S 9UnrpBZqqm4JAonsRPagj1kADq8Z+VlW/WU0939DN04oNNz3IrBwuR5Hw0gCOCyy h3yuSJqRaB2JZjVzL8skStnjqsKLMsDHRBZy36HeO7Sko/xfkf5Q9/Z2c+BGlUfq C+sA49EjBqQ= =qCeu —–END PGP SIGNATURE—–

Response:

I hope you read my second posting on this thread (the very next day), where I gave the reference for this, namely from the pharmaceutical chemists at Novo/Nordisk. These are the people who *manufacture* insulin, and know its chemistry better than anyone else. They are on a different plane entirely than doctors. If you think that doctors are the last word on medications, you grossly overrate them. You may have confused NPH and Ultra-Lente. Lente’s cannot be mixed with Regular. Lente’s structure is soluable with regular and will cause un-predictable peaks.

As a person who has gone out of his way over the last year to learn everything in print about insulin and its manufacture, and as an insulin-dependent diabetic for nearly 31 years, the last thing I would confuse is NPH and Ultralente. (During my first year I was on NPH, until it was discovered that I was allergic to the protamine, a protein taken from the sperm of the rainbow trout.) As for your own knowledge, Lente’s "structure" is NOT soluble with regular, not in the least. What happens when regular enters the solution making up Lente is that due to the higher zinc concentration of Lente, the insulin in solution from the regular starts to precipitate and form *more* of Lente’s component that is called Semilente (amorphous precipitate). Since this takes at least 12 hours to complete, a person who mixes regular and Lente gets a rather indeterminate effect. This is because in addition to the time these two insulins come in contact in the syringe, they also spend many hours of time together at the injection site. Hence, gone is the sharp peak of regular, but neither does the person get the full effect of added Semilente. A "poor" scene, to say the least. Michel Martin Devine

Response:

= = = Well, for one thing, Greg, you are NOT supposed to mix Regular with = NPH. The Regular will interfere with the insulin crystals assembled with = zinc and protamine in the NPH preparation. If you read the = sheet of paper that comes with NPH, it should say never to mix = it with Regular. = =Please note that I said "should say". I didn’t say that it "did say". =There’s a big difference. Yup. As usual, Mickey uses "argument from authority," with HIMSELF as the authority. No matter how much evidence against his bullshit is presented, since Mickey considers himself the ultimate authority on everything, that evidence doesn’t count. I try very hard to say exactly what I mean. I’d appreciate it if you’d bear that in mind and not try to "interpret" my posts to fit your own preconceived notions if I’m posting in a serious thread. Remember: If you throw a strawman into a heated debate, flames are likely to be the result.

Response:

– Hide quoted text — Show quoted text -I, Michel Martin Devine, am replying to my own posting for the purpose of extending what I said about mixing R and NPH, and will give a highly reliable source for my statements. I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular. Now let me quote a line or two from the "Galenics of Insulin" by the staff of Pharmaceutical Chemists at Novo/Nordisk, lead by Jens Brange: [snip] I didn’t say it the first time I responded to this thread, but I will say it now. Steve Kirchoefer’s admonition notwithstanding, the idea that your best interest lies in following the advice of your physician is not that foolproof. Here we have an example of doctors commonly telling diabetics to do something that is an absolute no-no. Mixing R with NPH both loses at least part of the action of the R, AND messes up the crystalline structure of the protamine crystals. How could anything be worse? Lesson: check out everything you do in your diabetes management through your own study, and don’t just take your doctor’s word for everything.

I would sooner listen to my doctor than Mickey. Surprised!?!! 30/70 insulin is regular/NPH which has been premixed by the manufacturer. Get a clue, Mickey. Mixing regular and NPH is far from an "absolute no-no". Mickey’s information is clearly wrong. This is hardly surprising, given Mickey’s track record for accuracy in his postings on mhd. The mixing of regular and NPH is commonplace in clinical practice and is fully supported by major insulin manufacturers. To imply that doctors are wrong to instruct patients to mix these insulins is an amazing public display of ignorance. If anybody out there is so foolish as to listen to Mickey’s medical advice on the internet over that of their personal physician, I would offer the suggestion that they might want to archive the postings that they are following. A lawyer might find them interesting in the future. :-) — Steve Kirchoefer Naval Research Laboratory Washington, DC 20375-5347

Response:

= = = = Have I forgotten some secret about mixing…am I correct in assuming = the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and = 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t = think things changed that much. = Thanks. = = = Well, for one thing, Greg, you are NOT supposed to mix Regular with = NPH. The Regular will interfere with the insulin crystals assembled with = zinc and protamine in the NPH preparation. If you read the = sheet of paper that comes with NPH, it should say never to mix = it with Regular. = It is common and approved practice to mix NPH with regular. Martin may = be rembering out of date information. To qoute from Kahn and Weir, = =Please read my subsequent posting that I made on Tuesday on this =thread from a source pretty close to the horse’s mouth, and very up to date. = = _Josliin’s Diabetes Mellitus_ 13th edition: = Currently, in mixtures of NPH and Regular insulin, = the regular insulin retains its potency in a stable = fashion for prolonged periods. This is true for = human insulins as well as for animal insulins. Unlike = in the past, all the preparations of NPH insulin = currently available from the major pharmaceutical = companies have similar levels of protamine and do = not contain excess prtamine that might bind to the = added regular insulin. = =This is where the error is in Joslin. And in Lily’s package inserts, and in all sources anybody has quoted excepf for the ONE source upon which you base your claim, eh, Mickey? Of course, just because all the other sources contradict Mickey doesn’t mean that Mickey’s once again posting uninformed bullshit and/or lies, now does it? =* Mixtures of NPH and regular = insulin at any of the ratios needed for clinical = purposes can be used without resulting in any = difference in clinical effect compared with that = produced by separate injection of each of the insulins. = =The catch here is the word "clinical". That’s right, Mickey: Clinical means when you’re actually using it to treat diabetes, rather then when you’re just looking to see what changes occur in the mixture. If the clinical effects are unchanged, shit-for-brains, then the observed changes DO NOT MAKE ANY DIFFERENCE WHEN YOU’RE ACTUALLY TRYING TO TREAT DIABETES. Why are you too stupid to understand that? =The chemists at Novo/Nordisk =have expressed their position on the effect of mixing the two insulins, =regular and NPH. Yup: Some of the R ends up precipitating out as NPH. This precipitate ends up coating the crystals of NPH. Now, let’s look at what that means, shall we? The precipitate acts more slowly than the R, but more quickly than the NPH. For clinical purposes, the two effects of which you make so much cancel each other out. =Despite whatever "studies" that Joslin could possibly =make, one cannot rule out the possible, I.e., Joslin actually studies the clinical effects, but since the studies don’t agree with Mickey’s typically moronic (and deeply flawed) analysis, the studies don’t count. =greatly adverse effects that =certain people engaging in this chemically unsound practice might =experience. And in Greg’s case, such is certainly the case. As usual, when faced with something he doesn’t have the necessary data to explain, Mickey starts bullshitting. Has anybody else noticed that when Mickey’s arguments have the least actual basis, his claims are the strongest? I try very hard to say exactly what I mean. I’d appreciate it if you’d bear that in mind and not try to "interpret" my posts to fit your own preconceived notions if I’m posting in a serious thread. Remember: If you throw a strawman into a heated debate, flames are likely to be the result.

Response:

I’ve been mixing NPH & R for 22 years, with nary an adverse effect. This question came up about ten years ago (not here, of course) and I tried two months of giving myself separate injections, keeping meticulous records and noting how I felt. The results: no difference. Aside from all the technical/clinical input, if you are comfortable with your control and administering insulin to yourself, try separate shots of NPH & R for awhile, then combine them and see if you have any perceivable change. What many doctors, and the like, loose track of is that diabetes is an INDIVIDUAL condition- everyone is different. They like to treat us as a herd of cattle, "We all have diabetes, we must all be the same and react the same"; this is big time fallacious, and you might bear the brunt of their error. I’ve met few doctors et al, who are diabetic and they are radically different in their views from the mainstream of medical practitioners. No one knows you or how you feel but you; don’t let them convince you otherwise. Sorry, went crazy for a moment…. Ray-

Response:

– Hide quoted text — Show quoted text – I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular.

Really? That contradicts what the insulin "users manual" from Eli Lilly says, and what two different books from The Joslin Diabetes Center say, not to mention what my endocrinologist told me. Everything I’ve seen in print says to draw the regular (clear) insulin into the syringe first, then draw in the NPH, Lente or ultralente (cloudy) insulin on top of it, then inject. –Paul E.

Response:

Can’t argue with this, except to point out that in the context of your advice, and the absence of other references to commonly- accepted and commonly-performed practices of mixing insulin, your remark was open to misinterpretation. Further, if you are going to make remarks like that, and have the ability to find reference texts in medical libraries, why not ask a friend or a physician or a pharmacist to see the patient information sheet? First. [Mills' remarks about Lilly Humulin mixing instructions, basically that Lilly sez it's OK to mix R and NPH] Jonathan, I think you have only read the posting that I made on Monday.

That is correct, I hadn’t seen the other posting. On Tuesday, I gave my source of information on all this, specifically the work of the Novo/Nordisk chemists who make insulin. Their reasons for NOT mixing R and NPH are quite compelling, and I feel quite justified in citing their work.

It was interesting, but no quantitative information on the rate of conversion of R to NPH was given. The Novo/Nordisk chemists never did say that ALL of the R is converted to NPH, nor were factors of variability and their effects discussed in detail…which suggests, given the clinical studies, that it is OK TO MIX R AND NPH. But here is another reality check (and this one I want to hear Mickey explain …which is… Novo/Nordisk sells a NovoPen cartridge pre-filled with 70%NPH/30%R human insulin! Given this fact, it seems likely that the reaction between R and NPH, while existent, is for the vast majority of diabetics of little significance in maintaining good control, especially if they are consistent in mixing their split R/NPH dose and administering it. A more likely cause for Greg’s problem was that he switched to a Medi-Jector which increases dispersion of insulin at the injection site: Greg may have been depending on ‘pooling’ caused by using a needle, and the subsequent slower onset of insulin to keep his bGs low overnight. What people do is their own business. But I think that when someone comes along like Greg who is experiencing understandable problems by engaging in this questionable practice, someone else like myself should be allowed to clue them in as to what they are up against.

Agreed, but let’s try to consider ALL elements in the case, not just those that are of specific personal interest. And since a physician is -trained- to look for all possible causes and symptoms that can lead to lack of good control, the best advice still is: Commentary in this newsgroup IS NOT MEDICAL ADVICE! See your physician (and bring in anything you saw here, if you think it will help you explain something), and make changes only on his/her recommendation! Sincerely, Jonathan

Response:

I didn’t say it the first time I responded to this thread, but I will say it now. Steve Kirchoefer’s admonition notwithstanding, the idea that your best interest lies in following the advice of your physician is not that foolproof. Here we have an example of doctors commonly telling diabetics to do something that is an absolute no-no. Mixing Michel Martin Devine

And, of course, following Mickey’s, Steve’s, Carl’s, or my advice rather than your doctor’s IS SO MUCH SAFER. That is eSPECIALLY TRUE FOR mICKEY’S ADVICE. (Sarcasm set at 9.0 on the Richter scale). If you can’t trust your doctor on things about which you are ill informed, you need to get another doctor. If you can’t discuss what you have heard from RELIABLE sources with your doctor and trust his evaluation, get another doctor. If you can’t discuss what you have heard from unreliable sources with your doctor and trust his evaluation, give up, there is no hope. Orville R. Butler,

Response:

Mickey, your problem is that you are *not* an expert on this subject! You lack the broad, general background knowledge to put what you read into any kind of relative context. This is why reading a book on a subject does not make you an expert. I am quite confident that these matters have been adequately resolved by the pharmaceutical companies involved, or they would not advise people that it is OK to mix R and NPH. You can rest assured that if you read something in the technical literature which flies in the face of established practice, you are probably missing something. Do you seriously think that the manufacturers would be advising people that it is alright to mix NPH and R themselves, and would sell NPH and R premixed, if there was an unresolvable problem with doing so? Do you believe that Novo-Nordisk is ignoring their own in-house experts and doing an "absolute no-no"? *I don’t think so!* — Steve Kirchoefer Naval Research Laboratory Washington, DC 20375-5347

Response:

There you go again, Steve. I am relating information from a source that would normally be considered far more reliable than some doctor or doctors. This source is the definitive book written on the subject of insulin entitled "The Galenics of Insulin", by Jens Brange et al who are the pharmaceutical chemists in charge of the manufacture of insulin at Novo/Nordisk. Steve, do you know of a higher, more reputable source than that? Me, I am just telling people what I found out from this source. I did NOT make it up on my own. It so happens (if you read pp. 48-49 of this book), that regular insulin when it meets up with some free protamine in solution, and there is always at least some of that present in NPH due to the necessity of there having to be an excess and not a shortage of it to make insulin crystals using protamine, that at least part of the dissolved insulin from the regular will precipitate. It does take time to do this, and there is plenty of time for it to happen, whether the insulin is in the syringe or in the body at the injection site. Also, even if this effect can be diminished by painstaking minimalization of the surplus level of protamine, it also happens that the insulin in solution can bind to the protamine in the insulin crystals themselves in NPH, and this will not only drain off at least some of the dissolved insulin that was taken for a quick acting effect, but will certainly have an effect on the timing of the crystals themselves. The only reason I brought this up was because Greg was having all sorts of weird experiences while mixing R and NPH, which is not at all surprising. And I feel that I was acting perfectly responsibly in doing so. Just because you feel that you know more than the pharmaceutical chemists who make insulin gives you NO call to post drivel like this in an attempt to cast aspersion on the "bearer of bad news". Where in world did you come from? Before posting stuff like this, one can save themselves a some embarrassment by putting in the minimal amount of effort it takes to check things out. Don’t claim that package inserts say something which they do not say.

I never said that and you know it (Steve Kirchoefer learned his argumentation techniques from you know who). I said that they *should* say that R and NPH are not to be mixed, and my original posting is still there where anyone including you can plainly see what I said. Mixing NPH with Regular is *standard* practice.

That’s the line of reasoning called "Well everybody does it…" That doesn’t make it right, much less advisable. It is generally not recommended that one mixes Lente insulin with Regular, since the Lente with convert the Regular to Lente if enough time passes after mixing prior to injection. Even so, it is OK to mix these provided that you don’t wait too long to inject.

Fine, but that is not at issue on this thread, just some background info. One should defer to a physician’s judgement on these matters, and not take meaningless and possibly dangerous advice over the net from people you don’t know.

Here you are strictly running off at the mouth. 1) I was not offering advice, just relating information. You used to pontificate that such was the purpose of misc.health.diabetes. But you can’t even stick to your own so-called principles, which I am beginning to see you really have none of. 2) Dangerous? If a person *didn’t* mix their R with their NPH and decided to be prudent and inject them separately (I have read postings by people here on m.h.d. who do exactly that), how in the world by the longest stretch of the imagination could that be a dangerous act? Strawman Steve. Does anyone have a match? Furthermore… Why shouldn’t a person be informed on what a truly reputable source has to say about the matter of mixing R and NPH? How does the person doing the "bird-dogging" come into the picture? Does Albert Einstein have to be quoted only by Albert Einstein? You Steve Kirchoefer are strictly arguing ad hominem, basically stating that if I said it, it can’t be true. This time you really got yourself out on a limb. You make me sick!

Response:

WAY WRONG… NPH and Regular can be mixed. They do not interfere with each other. I used to be worried about long term mixing (overnight). I talked with doctors and read the info on them, I now have no problem mixing my daughters morning shot the night before when she stays at grandma’s. You may have confused NPH and Ultra-Lente. Lente’s cannot be mixed with Regular. Lente’s structure is soluable with regular and will cause un-predictable peaks. — (414) 563-8456 ext. 214 || and Damn Proud of it!!! || * / W6340 Hackbarth Road, Fort Atkinson, WI 53538-8999

Response:

Please note that I said "should say". I didn’t say that it "did say". There’s a big difference. – Hide quoted text — Show quoted text – The information for the patient provided by Lilly about NPH Humulin states that NPH should be mixed only with R Humulin, and provides the instructions for doing so. Thinking that perhaps Mickey was recalling instructions for Ultralente Humulin, I checked that sheet, too. It stated that Humulin U should be mixed only with R or Lente Humulin and only on the advice of a physician. And then -this- sheet provides the mixing instructions, too. I suggest that each user read the sheet of paper for him/herself, especially as mixing instructions may vary for different types and brands of insulin (which I can’t speak to, as I do not have other patient information sheets). Mickey’s advice, which is false for Lilly Humulin R, NPH, Lente, and U, is a very good example of why each of us should be careful to rely on the net only as a starting point to become better educated. And as always, make changes in your regimen in consultation with your own, hopefully trusted, physician. Sincerely, Jonathan Mills

Jonathan, I think you have only read the posting that I made on Monday. On Tuesday, I gave my source of information on all this, specifically the work of the Novo/Nordisk chemists who make insulin. Their reasons for NOT mixing R and NPH are quite compelling, and I feel quite justified in citing their work. What people do is their own business. But I think that when someone comes along like Greg who is experiencing understandable problems by engaging in this questionable practice, someone else like myself should be allowed to clue them in as to what they are up against. Michel Martin Devine

Response:

I, Michel Martin Devine, am replying to my own posting for the purpose of extending what I said about mixing R and NPH, and will give a highly reliable source for my statements. – Hide quoted text — Show quoted text – I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular.

Now let me quote a line or two from the "Galenics of Insulin" by the staff of Pharmaceutical Chemists at Novo/Nordisk, lead by Jens Brange: p. 49: The… insulin mixture regular/NPH… [is] not physically stable, as some of the soluble insulin binds to the protamine insulin crystals. [this both reduces the amount of action from regular insulin and modifies the structure and timing of the protamine insulin crystals]. [Also,] …It appears that… some of the regular insulin precipitates immediately after mixing [this is in addition to the regular insulin that binds to the protamine crystals] and the proportion of insulin remaining in solution decreases with time, with decreasing ratio between regular and modified insulin [in this case protamine zinc insulin] with increasing strength of the preparations [meaning this effect is more pronounced by far in U100 than it is in U40]. I didn’t say it the first time I responded to this thread, but I will say it now. Steve Kirchoefer’s admonition notwithstanding, the idea that your best interest lies in following the advice of your physician is not that foolproof. Here we have an example of doctors commonly telling diabetics to do something that is an absolute no-no. Mixing R with NPH both loses at least part of the action of the R, AND messes up the crystalline structure of the protamine crystals. How could anything be worse? Lesson: check out everything you do in your diabetes management through your own study, and don’t just take your doctor’s word for everything. Michel Martin Devine

Response:

- Hide quoted text — Show quoted text – Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular. It is common and approved practice to mix NPH with regular. Martin may be rembering out of date information. To qoute from Kahn and Weir,

Please read my subsequent posting that I made on Tuesday on this thread from a source pretty close to the horse’s mouth, and very up to date. _Josliin’s Diabetes Mellitus_ 13th edition: Currently, in mixtures of NPH and Regular insulin, the regular insulin retains its potency in a stable fashion for prolonged periods. This is true for human insulins as well as for animal insulins. Unlike in the past, all the preparations of NPH insulin currently available from the major pharmaceutical companies have similar levels of protamine and do not contain excess prtamine that might bind to the added regular insulin.

This is where the error is in Joslin. We were not talking about mixing Regular with Protamine Zinc Insulin. Yes, it is true that the excess protamine in PZI will cause the Regular to precipitate, but that is irrelevant to the issue of mixing Regular with NPH. However, there is and has always been a problem with the regular insulin in solution binding with the protamine insulin crystals of NPH themselves (when these two are mixed), and this happens irregardless of how much excess protamine there may be left over in PZI: we’re talking about NPH where very little if any free protamine exists. This is all explained on p. 48-49 of "Galenics of Insulin" by Jens Brange. Charles, you can read this book in the Biomedical Library of the UCSD Medical School, which is close to where you work. I have a copy of this work open beside me even as I keyboard these words into my computer terminal. * Mixtures of NPH and regular insulin at any of the ratios needed for clinical purposes can be used without resulting in any difference in clinical effect compared with that produced by separate injection of each of the insulins.

The catch here is the word "clinical". The chemists at Novo/Nordisk have expressed their position on the effect of mixing the two insulins, regular and NPH. Despite whatever "studies" that Joslin could possibly make, one cannot rule out the possible, greatly adverse effects that certain people engaging in this chemically unsound practice might experience. And in Greg’s case, such is certainly the case. And a great many more people could be experiencing such deliterious effects without even being aware of it. *ref. cited This is, of course, not true with the lente insulins.

Nobody said it was. I have explained on several occasions the pitfalls of mixing regular with the lente insulins, and have even experienced them myself in very recent history. Michel Martin Devine

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: Well, for one thing, Greg, you are NOT supposed to mix Regular with : NPH. The Regular will interfere with the insulin crystals assembled with : zinc and protamine in the NPH preparation. If you read the : sheet of paper that comes with NPH, it should say never to mix : it with Regular. Huh? No such thing! It’s perfectly FINE to mix R with N, and that, in fact is what 70/30 IS — a mixture of 70% N with 30% R. NPH is balanced so that it doesn’t affect the R when mixed in a syringe. The only reason you don’t want to contaminate your R BOTTLE is because when you’re shooting plain R, you don’t want to have an effect from N as well. But when you’re mixing, it’s fine. I don’t know where you got that info, Mickey, but if you consult any CDE or endo or the manufacturer, they will tell you mixing N and R is fine. Smiles, ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- Natalie A. Sera, AKA Dr. Quack, with all her ducks in a row!!!! ___ Type / 3, MI 4x (3Rs and an N) a year and a half! Proud mother of Josh, age 22 ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._c- ._(` ._c- ._c- ._c- ._c- ._c- Can YOU find the Ugly Duckling?

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- Hide quoted text — Show quoted text – I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular. As for your question in the last paragraph, one of the chief disadvantages of NPH is that it does not allow you to do-it-yourself mixing.

I have two diabetics kids on mixed Humulin N and Humulin R. We have been mixing since day one. On occasion we prepare mixed needles ahead of time for my mother-in-law to inject since she can handle the injection but is afraid that she will make a mistake in mixing. The diabetes team at the center where we take our kids tell us that the new insulins can be mixed and left in the needle for several hours without significant change in the absorption characteristics. We have seen much more variation in insulin action related to location of injection (stomach injections differ from arms, legs etc.) than from mixing. Currently we do all morning injections in the stomach and rotate supper dose to arms, legs and buttocks. Regards … James

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The information for the patient provided by Lilly about NPH Humulin states that NPH should be mixed only with R Humulin, and provides the instructions for doing so. Thinking that perhaps Mickey was recalling instructions for Ultralente Humulin, I checked that sheet, too. It stated that Humulin U should be mixed only with R or Lente Humulin and only on the advice of a physician. And then -this- sheet provides the mixing instructions, too. I suggest that each user read the sheet of paper for him/herself, especially as mixing instructions may vary for different types and brands of insulin (which I can’t speak to, as I do not have other patient information sheets). Mickey’s advice, which is false for Lilly Humulin R, NPH, Lente, and U, is a very good example of why each of us should be careful to rely on the net only as a starting point to become better educated. And as always, make changes in your regimen in consultation with your own, hopefully trusted, physician. Sincerely, Jonathan Mills

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I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Sure, it’s been a while since I’ve mixed, but I didn’t think things changed that much. Thanks. Greg — —–BEGIN GEEK CODE BLOCK—– Version: 3.1 GCS d- s+: a– C+++$ UVHISX++$ P+++ L+++ E+$ W++ N++ o+ K w—$ !O M++$ !V– PS PE !Y+ PGP++ t+ !5– X++ !R tv+ b++ DI++++ D++ G++ e h(!) r–* y+* ——END GEEK CODE BLOCK—— ======http://acm.cs.umn.edu/~torgo======

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Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular. As for your question in the last paragraph, one of the chief disadvantages of NPH is that it does not allow you to do-it-yourself mixing. To do that you have to use the insulins made withOUT protamine. But when you mix Regular with either Humulin L or Humulin U, you will get some strange results from the Regular. Some of it will form amorphous precipitate due to the presence of free zinc in the L or U, while some of it will remain as Regular (just insulin in solution). It all depends on which way you want to go. People who do this who want and need their Regular to remain Regular and nothing else take their Regular as a separate injection. Others who want it to become mostly amorphous precipitate have to mix the two in the same syringe and wait at least 12 hours before using it (by this I mean they mix it up well in advance of need, which gets to be a pain having to be prescient as to exactly how much insulin they are going to take the next day). This route has the limitation as to how much free zinc is in the Lente or Ultralente preparation to act in the formation of the amorphous precipitate. After a certain point, when all the free zinc has been used up, no more Regular can be turned into amorphous precipitate. Then there are still other people who seem to be happy with what they get by mixing Regular with a form of Lente and taking it, which gives them part Regular and part amorphous precipitate. From my thirty odd years of experience in mixing insulins, the way that gives the best and by far the most consistent results is to have one vial of purely crystalline insulin (this is available as Humulin U for Ultralente) and another vial of purely amorphous precipitate of insulin. Presently, no insulin manufacturer makes the latter (which they used to market as "Semilente"), but what I do is raise the level of zinc to a specific amount in a vial of Regular, and let it stand for 24 hours. This is how long it takes for sure to convert all the insulin in solution to amorphous precipitate. Then after another 24 hours in the refrigerator, the amorphous precipitate then cures and settles out to its normal level at the bottom of the vial, whereupon it is ready for use. Some day, Lilly Co. may be prevailed upon to supply a Humulin S (S for Semilente, the traditional brand name for amorphous precipitate).

Response:

– Hide quoted text — Show quoted text – I’m trying to switch from 70/30 to regular & NPH (at the advice of my doctor), and I’m getting all kinds of weird results, all at night. I’d been on 70/30 for about past 6 years, and started out doing 70% NPH and 30% regular of my old 70/30 dose, since this seemed like the logical thing to do. To make a short story long, I have yet to get any kind of reliable control, even with increasing my nighttime dose to be larger than my morning. Have I forgotten some secret about mixing…am I correct in assuming the 70/30 mixture in the 70/30 is essentially the same as mixing 70% and 30% yourself? Well, for one thing, Greg, you are NOT supposed to mix Regular with NPH. The Regular will interfere with the insulin crystals assembled with zinc and protamine in the NPH preparation. If you read the sheet of paper that comes with NPH, it should say never to mix it with Regular.

I find this rather surprising, since I have been mixing the two since I have been on insulin. The mixing is only in the syringe; one draws the Regular into the syringe first, and then the NPH. The 70/30 prepared mixture is more mixed, and if anything, the interference would be greater there. It might be a good idea to do a little gentle shaking of the syringe, and to allow it to stand for a few minutes. Not too long, or separation can occur, just as it does in the NPH bottle, and it is easier to get the crystals back in suspension in a bottle than in a syringe. — Herman Rubin, Dept. of Statistics, Purdue Univ., West Lafayette IN47907-1399

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I’m sitting here with the insert from my Humulin N in front of me and it says: " 1. NPH human insulin should be mixed only with regular human insulin." And the insert from my Humulin R says: "1. Regular human insulin should be mixed with longer-acting human insulins only on the advice of your doctor." I’m appalled that Eli Lilly & Company has been misleading me for so many years…making me believe that it’s okay to mix the N and R. And shame on my doctor for prescribing it!!! -I’m done with my sarcasm – Where do you come up with your information? I’ve been mixing since 1972 – and have experienced no problems. (Although I personally don’t get into the painful details of the chemical compositon and reactions. I just use it and it works.) I hope that you haven’t scared too many readers of this newsgroup by your dictate that Regular and NPH should not be mixed… I usually just read the messages here, but you’re statement was so off the wall that I had to respond – if only to remind other readers that what they read here is not always gospel. Please re-read your inserts before quoting them and scaring people. Coleen Bloodgood

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be rembering out of date information. To qoute from Kahn and Weir, _Josliin’s Diabetes Mellitus_ 13th edition: Currently, in mixtures of NPH and Regular insulin, the regular insulin retains its potency in a stable fashion for prolonged periods. This is true for human insulins as well as for animal insulins. Unlike in the past, all the preparations of NPH insulin currently available from the major pharmaceutical companies have similar levels of protamine and do not contain excess prtamine that might bind to the added regular insulin.* Mixtures of NPH and regular insulin at any of the ratios needed for clinical purposes can be used without resulting in any difference in clinical effect compared with that produced by separate injection of each of the insulins. *ref. cited This is, of course, not true with the lente insulins. — Charles Coughran

Response:

[snip] Mickey is, once again, completely and totally wrong. It is perfectly OK to mix Regular and NPH, Mickey’s obtuse postings not withstanding. Don’t believe everything you read on the net. Some people like to spout off like they are authorities, when in fact they are clearly ignorant. Before posting stuff like this, one can save themselves a some embarrassment by putting in the minimal amount of effort it takes to check things out. Don’t claim that package inserts say something which they do not say. Mixing NPH with Regular is *standard* practice. It is generally not recommended that one mixes Lente insulin with Regular, since the Lente with convert the Regular to Lente if enough time passes after mixing prior to injection. Even so, it is OK to mix these provided that you don’t wait too long to inject. One should defer to a physician’s judgement on these matters, and not take meaningless and possibly dangerous advice over the net from people you don’t know. — Steve Kirchoefer Naval Research Laboratory Washington, DC 20375-5347

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