P.S. Regarding the claim I see in the media that insulin Regular entails too large a lag time, I don’t buy into this at all. My capillary BG is down at least 5mg/dL within 10 minutes after injecting human insulin (Regular). Considering the fact that there is a typical diffusion lag time of 1/2 hour between capillary and serum BG, my serum BG is likely down by several times as much within 10 minutes.
Fast-acting insulins may have shorter-acting times for T2Ds eating high-carb diets, but most T2Ds are not insulin-dependent (to prevent ketoacidosis) and so-called IR is a function of excessive dietary carb’s and subcutaneous body fat saturation.
T1Ds are less likely to have saturated normal body fat storage capacity and should respond like me. Otherwise the solution is the same as for T2DM – adequately reduce or eliminate the carb’s.
Regarding the claim I see in the media that insulin Regular entails too large a lag time, I don’t buy into this at all
P.S. Regarding the claim I see in the media that insulin Regular entails too large a lag time, I don’t buy into this at all. My capillary BG is down at least 5mg/dL within 10 minutes after injecting human insulin (Regular). Considering the fact that there is a typical diffusion lag time of 1/2 hour between capillary and serum BG, my serum BG is likely down by several times as much within 10 minutes.
You should do what works for you, but also understand that insulin analogues have made t1 easier, safer and more flexible. It is not just marketing and what works for you with NPH and R won’t necessarily work easily for someone else. Also one consideration that isn’t talked about enough is that just as many Americans cannot afford modern insulins, it would be just as difficult to afford to eat low carb in a healthy way.
Having used beef, pork and human insulin for more than 20 years before the analogs were available, I can tell you the difference for me was dramatic, all theoretical arguments aside. The even bigger issue was long acting NPH vs. what’s available today. I would not return to either except as a last resort.
My diabetes life has been split roughly equally between the older insulins and newer analogue insulins. There is no comparison between the two. I would never go back unless it was a matter of life or death. There was a very noticeable speed difference between Toronto (regular) and Humalog, and there’s been a similar speed difference between Apidra and Fiasp. Fiasp in the pump is amazing and allows not only quick corrections but also rapid adjustments in basal rates that wouldn’t be possible with other rapid insulins and especially not with short-acting insulin. I believe that NPH has been shown to be highly variable and, for me, it resulted in severe lows that required assistance from others.
There is no way regular would have any impact on my blood sugar after 10 minutes. Even Fiasp usually takes 15 minutes (and sometimes longer) before I see any movement, and it’s significantly faster than Humalog/Apidra were for me, which were themselves significantly faster than regular. If you have 40% of your beta cell function remaining, how do you know it’s not internal insulin secretion (which acts very rapidly) having such a fast impact on your blood sugar? I agree that regular would be useful if eating a diet very low in carbohydrates.
We are all different and need to find the combinations of insulin that work best for us and our diet and lifestyle. There is no one-size-fits-all for diabetes…if there was, this disease would be easy!
I guess that I should have been more clear – the experimental measurement of response time/lag is done in the fasted state, and not in conjunction with a meal.
In the fasted state there is no portal stimulation to increase, or significantly change at all, insulin or glucagon secretions (i.e. flux rates) from endocrine pancreas.
Dr. Bernstein, for example, recommends this means of measuring intrinsic response lag in a diabetic in his book. Certainly he claims (and even I believe) that T2Ds have much larger response lags than other types of diabetics, generally speaking. And a large response time would be found in only a minority of T1Ds.
In my opinion the general understanding of the characteristic “whole-body” insulin-resistant response, characteristic of T2DM, is very much incomplete. What is really going on in prandial response (i.e. exogenous insulin and meal, roughly concurrent) is the superposition of two basically independent time-response profiles.
- The first response is entirely contained in the peripheral (to portal vein, liver and islets) blood and tissues – that of driving PBG into tissues (largely muscle, and also adipose, kidneys, and other nonportal organs that express GLUT4). The portal system is isolated because peripheral insulin does not reach portal vein or liver – this has been verified in the lab using radiolabeling. For prandial conditions the portal BG is also massively higher than that in peripheral blood, and to a lesser degree this is still true for nonprandial conditions.
- The second response is that of the islets. This applies only to the prandial condition – otherwise the islets are quiescent, meaning hormonal flux is in the steady state, and hence hepatic hormone (e.g. endogenous insulin and glucagon, primarily) flux is also constant for the most part.
The monomers of dietary protein and carb’s, AAs (amino acids) and glucose (ignoring fructose and galactose which do not stimulate islets anyway), stimulate a roughly offseting increase in both insulin and glucagon (AAs) from beta and alpha cells respectively, and an increase in insulin and decrease (to zero in a nondiabetic) of glucagon. The alpha-cell response to portal glucose is indirect, resulting from the direct beta-cell increase of islet blood insulin (this is an inverse response – so-called paracrine endocrinology).
In a diabetic, due to a large deficiency of insulin response from beta cells, the alpha-cell response to portal glucose is inverted from that of the nondiabetic, meaning that glucagon secretion goes UP instead of down to zero. Usually by a factor of three or four. This is what generates the hyperglycemia of diabetes – the liver receives a signal to raise BG (i.e. hepatic arterial flux increases) via hepatic glycogenloysis. That is why a diabetic must synthesize and/or store more hepatic glycogen than a nondiabetic – there is a daily higher-than-normal drain from the liver due to a higher “area under the curve”, or total hepatic input, of glucagon. This has also been measured in humans and animal models repeatedly since the 1970s.
Negative feedbacks (as in the prandial response of a nondiabetic) are regulatory. Positive feedbacks are unstable. A diabetic has a positive-feedback response to dietary carb’s as explained above. A diabetic has a significantly lessened, but still negative, feedback response to AAs. That is why dietary protein can predictably compensate for excessive hepatic artery glucose flux in the peripheral (i.e. nonportal) tissues in response to dietary protein. But this is not true for dietary carbohydrate. Only once portal flux (from intestine) of glucose ends (absorption from meal is complete) can the portal system “equilibrate” and settle.
In most T1Ds and some (advanced) T2Ds, if endogenous insulin manufacture/secretion is close enough to zero, there is also a positive-feedback condition but this can occur in the fasting state. That is because islet blood insulin acts inversely directly upon the alpha cells to suppress glucagon. This phenomenon also has been measured in the lab.
That is why any diabetic with close to zero endogenous insulin production is “insulin-dependent” – that is, requires continuously adequate exogenously supplied insulin to prevent ketoacidosis which is a state of “runaway” glucagon production (raising both hepatic glucose output and ketones output).
All of the comments above are fair enough, but I sometimes comment herein – maybe somewhat provocatively by intent – because I know that precious few people (MDs or diabetics) have ever read the basic research literature generated by Roger Unger and many others since 1970, elucidating the fundamental endocrinology in both nondiabetes and diabetes. IMO the metaphorical models used in general to discuss diabetes are at best very misleading, and I think they are incorrect and hence lead diabetics and MDs to incorrect conclusions.
So in this particular example, tying things back to the two independent responses, each one has a time profile. The prandial response by islets will be immediate in response to AA and glucose portal flux. All delay or lag from ingestion to islet/hepatic response will be within the GI tract. Protein is very slowly and gradually absorbed, and carb is relatively rapidly absorbed. Triglycerides/fatty-acids/lipids are not absorbed portally at all, but can modulate absorption rate of the other two macronutrient monomers in a mixed meal.
In a typical T2D FA (fatty acid) intermediates are ectopically present in GLUT4-expressing cells such as adipose, myocytes, hepatocytes, beta and alpha, and so forth. This is the state in metabolic syndrome more generally, wherein adipose storage has first become saturated. This is often referred to as an IR state, which I think is a gross misnomer. Insulin pathways are involved, but do not even begin to adequately describe the pathological state of cellular derangement of MetS or T2DM. The pathways that are most severely disabled, by far, are those of the FAs (while glucose pathways are relatively more intact or partially functional). This is textbook material – nothing new or in dispute. Because the largest cellular energy users (e.g. muscle, including heart) in the body have largely disabled fatty-acid metabolism they become pathologically dependent upon glucose for fuel, and this in turn robs from the brain (which does not metabolize FAs for energy). That is why people with MetS become hungry every few hours, once the peripheral blood glucose level begins to drop after a previous meal.
It is as a result of this metabolic derangement of most GLUT4-expressing cells that peripheral (i.e. exogenous) insulin fails to act with minimal (i.e. normal) lag to drive BG into tissues. Meanwhile, the islet glucagon response is just as immediate as it is in a nondiabetic. So peripheral BG rises until the slowed peripheral action of injected insulin finally can take effect. Many diabetics are taught to inject as much as one hour before meals to partially compensate.
It is certainly possible for any type of diabetic to saturate subcutaneous adipose capacity and generate metabolic syndrome. It is just the rule in T2DM and not usually the case for T1DM (or HNF monogenic diabetes).
So my questions, or challenges, to those who have read what I suggested about use of human insulins would be:
- Have you tried the experiment that Bernstein recommends – not with a meal; everyone who uses insulin has probably done that, but using a small injection (2U for example) after all previous meals have been absorbed? I think that anyone not with MetS would have a response well within a half hour, but am willing to be proven wrong. Bernstein’s experiment makes sense because it characterizes the metabolic status of the peripheral insulin-sensitive tissues such as muscle, and there is no prandial/hepatic response working on top of the peripheral insulin response to completely confound the results.
- Regarding fast-acting insulin analogs, I acknowledge that these will compensate earlier and more in response to dietary carb’s. Is everyone responding including significant carb’s in meals? If so, OK and that is one’s personal choice, but I doubt any long-time diabetic would claim that BG regulation can be as consistent and regular with carb’s vs. without. I characterize “low-carb” for a diabetic as a meal content low enough that the individual cannot distinguish any difference in bolus insulin injection required to minimize BG perturbations between a typical mixed meal and an experimental “no-carb” meal (e.g. all meat) with equivalent amount of protein.
And if that criterion can be met, then the 2nd criterion is to roughly match minimum-to-maximum BG during prandial interval between mixed meal and no-carb/ideal meal. The positive feedback of glucagon response to portal glucose will tend to generate both hyperglycemic and hypoglycemic peaks during the prandial period – positive feedbacks are oscillatory in nature.
The long-term tradeoff to think about in determining what degree of BG transient is acceptable is that of the complications of diabetes. This is a slow, silent process. I was a “mild” diabetic for over 50 years before self-diagnosing. I was tested for extensive and in many cases quite unusually advanced complications (i.e. tissue death/loss), none of which I was previously aware of. I do not get quite as high as 180mg/dL eating a conventional (high-carb) meal (without insulin injections) – close but not quite. That is typically the threshold for polyuria which I have never experienced in my life, despite being born diabetic. And it is the prandial transients that cause almost all of the damage. MODY2 results in no diabetic complications, ever. Typical basal/fasting BGs are 150mg/dL in glucokinase MODY. The cells compensate in the long term – they cannot compensate in the short term. Brownstein’s research had pretty much worked out all of the underlying cellular mechanisms more than 15 years ago.
- Regarding long-acting insulins, I guess I am curious if any responding T1Ds have tried to interleave using NPH and Regular as I suggested. Time profile for Regular is ~4 hr and for NPH is ~8 hr with ~4 hr lag (of zero flux). I noticed that Dr. Bernstein has at least acknowledged (in some of his online seminars) that NPH might, or does, work well at bedtime to cover dawn phenomenon. Bernstein, for himself and most of his T1D patients, has found that a mid-sleep 2nd injection of most long-acting insulins is required. Tresiba is the only (fairly recent) exception since Ultralente was discontinued.
Anyway, I used the observation(s) of reduced market supplies of insulin analogs as a pretext. I use Bernstein’s observations of 5k to 10k diabetic patients over his MD career to try to bridge the gap between my own personal experience and what might work for a T1D, as well as my reading of the basic research.
For my own part, I do not qualify for insurance coverage for anything as a result of the monogenic diabetes – nothing. Why? Well … the clinical guidelines (ADA in US, WHO elsewhere, and these are almost identical anyway) do not recognize or address genetic forms of diabetes at all. Until the 20% beta-cell function threshold is crossed, resulting in recognizable symptoms, the guidelines consider one to be nondiabetic – full stop. That does not make my extensive and advanced diabetic complications any less a reality.
Before I realized that I could treat myself I saw Dr. Bernstein – he is the one who did the extensive physical exam on me. He prescribed all insulin analogs for me, which was very expensive (but so was his time; he does not work with insurance, and so I had to pay cash prices, typically five to ten times what insurance companies contract, for insulin and medications), and I followed his prescriptions for almost a year. For myself, I found that the fancy, expensive insulins actually were less effective in every respect than my own program. Insulin aspart was inappropriately fast-acting and did not match my ultra-low-carb meal absorption time profile – I think Bernstein prescribed it to try to cover meals and dawn phenomenon with a single insulin. But I find it unnecessary to cover the dawn phenomenon as well. The insulin detemir never worked as well during fasting intervals (especially dawn) as the NPH does, in my experience. And the long-acting insulins are fragile and have short half lives (the latter maybe not being as big an issue for T1Ds, but I do use 8U in two injections daily of NPH which is not trivial).
So that is the backdrop I am coming from. It seems to me that a whole lot of diabetics who might find insulin analogs unaffordable or inaccessible could probably get along pretty well with human (disparagingly referred to as “Walmart”) insulins. Obviously all did up until the last couple of decades or so. I myself thank my lucky stars for Walmart and the insulin makers and states that cooperate to provide this public benefit.
- Low-carb meal costs have been discussed ad nauseum by many, many others – I need not repeat. But the point is that they can be very cheap, and are so for me. I eat a lot of liver, bone (broths), cheap whole cuts of meat, eggs, and cheese. These mostly range from $1 to $6 per lb. I could easily cut the high end of the range down to $3 per lb if I had to. Whole plant foods are more expensive. Eating out is more expensive. Only heavily refined (i.e. industrial) foods are cheaper. Good luck with the latter, regarding diabetes and health in general.
- T1DM vs. other types: My final comment relates to the value of understanding the endocdrinology. In longstanding T1DM and in advanced diabetes (with little to no endogenous insulin production) generally there is an epigenetic transformation of the alpha cells. This takes several years to go to completion, typically, after beta-cell insulin production nears zero. The transformation is a response to the loss of the insulin signal in islets. The research literature refers to the phenomenon as the “loss of intraislet insulin decrement”. Of course, once all insulin secretion goes to zero there can be no “decrement”. The decrement is a signal (that is very powerful in its first derivative with respect to time) to the normal alpha cell to secrete more glucagon to raise BG, normally in response to incipient hypoglycemia.
Genetic expression changes in cells occur in response to long-term changes in their signaling environment. It is hard to interpret changes induced by nonevolutionary modern pathophysiological derangements such as T1DM, but epigenetic responses to changes in environment generally are adapted survival characteristics. Beta cell populations in rodents, for example, vary by several-fold every year in response to seasonal changes. Populations go up in summer when plant foods are abundant, requiring more insulin response, and down in winter. Modern hominids, being evolved as supercarnivores for 2.5 million years, have almost no capacity to grow/replicate new beta cells after the age of five. There was no evolutionary drive to do so.
Anyway, most T2Ds will not undergo the alpha-cell transformation. I will certainly not – my diabetes is not progressive at all. Very few T1Ds will avoid it. The result is an increased sloppiness (sort of like a mechanical “backlash” or hysteresis) and time lag in response to hypoglycemia.
If I inject too much bolus insulin for a meal my BG goes down to that of a prolonged fasting state (in the 50s). I am completely unaware unless I measure. I have no change of sensation of any type, including in brain. That is because hepatic ketosis is increased immediately, and fully adequately, in response to declining blood glucose, keeping the brain completely fueled without the slightest hiccup. I can watch this happen with a ketone meter and BG meter, realtime.
When I do endurance runs (weekly) I can drive my BG down into the 30s easily. In the 40s I still feel nothing. If I get down near 30 I sometimes feel a temporary slight nausea only after finishing the run, maybe for five or ten minutes. But otherwise still nothing.
Doing these things would be relatively dangerous for a T1D. For the physical exercise T1Ds take dextrose and generally go somewhat hyperglycemic for safety margin.
Not only does peripheral insulin not reach the islets, but also islet blood insulin levels are much higher than peripheral in nondiabetics. Prandially they can be 400x as high. So the intraislet signal is just too weak to be recognized by the alpha-cell genome.
Personally, if I were a T1D I would find it useful to understand the paracrine endocrinology of the islets. It has a practical consequence.
Similarly, it has been well recognized since the 1970s that in T2DM there is a normal (equivalent to nondiabetic) response to AAs – this remains intact until T2DM becomes well advanced. This is not true of T1DM or of HNF MODY (my type). Researchers studied this during the 1970s, but thereafter (to my knowledge) no one has. This is very interesting, I think, and should provide an avenue to better understand T2DM. But the pharmaceutical industry is completely glucose/insulin-centric, for a number of different reasons.
Nevertheless, it is very well recognized (e.g. research of Nuttall and Gannon, and general clinical experience) that early-to-intermediate stage T2Ds can control BG without the use of insulin by eating very low-carb diets. Lucky them, if they take advantage.
After I had self-diagnosed in 2010 and monitored myself for a few years, I decided to see Dr. Bernstein in 2014. I had not yet figured out that I could not be a T2D or T1D and was in fact HNF1-alpha. I did not know enough yet. My justification for seeing Bernstein is that I knew he would prescribe insulin for me. And I knew of noone else in the world who would.
So I did see Bernstein. He knows virtually nothing at all about monogenic diabetes. He has never written a word about it to my knowledge. I finally heard him mention it once many years after I saw him, in one of his online seminars.
Bernstein has many times stated that he does not care what type of diabetes a patient has, because he will treat so as to normalize BG as best as possible for each individual case. IMO Bernstein has read virtually none of the basic research in diabetes from 1970 onward. And it certainly shows – he has no understanding of the paracrine islet endocrinology, hepatic function, and so forth. Glucagon is by far the most powerful hormone in the body – far more powerful than insulin as a hepatic regulator, gram for gram. It has to be – it keeps the brain fueled and alive continuously. Insulin is an anabolic hormone – it is not vital for life on a second-to-second basis. Anabolism is important in an evolutionary context, for reproduction mainly. But there is no comparison between the vital functional important of glucagon and that of insulin.
Bernstein has stated that glucagon is a secondary hormone (to insulin). This is stunningly ignorant for someone in his field.
Why is this theory important? Well, for one thing there has been some interest in academic circles to find a long-term therapy for T1DM by various means of glucagon inhibition. Very interesting studies in animal models have demonstrated proof of concept. Metraleptin and genetic engineering have been most successful. Rodents normalize BG for as long as a year or so. But then they revert back to full-blown diabetes. Why? Same reason as the epigenetic response to the loss of intraislet insulin in advanced diabetes. There are always many redundant genetic and metabolic pathways in organisms, most especially for the most vital functions such as fueling the brain. That is why, IMO, glucagon inhibition will never work in the long run. There will always be an evolved epigenetic response to restore a parallel pathway to generate glucagon. I also think that the basic researchers working for Novo Nordisk, Eli Lilly and others (some of whose work I am familiar with) understand this, and some (but not all) of the academic researchers also do.
So if I were a T1D I would be even more interested if anything.
For my own type, HNF1-alpha, I find Bernstein’s attitude annoying and unhelpful (I might say selfish). When I went to see him my best guess was that I might be a T2D (in the pre-diabetic stage by ADA guidelines) even though many things just did not add up. But I knew that T2DM had been reversed in the long term in many, many small clinical study cohorts that fasted (or mimicked fasting with a very-low calorie, protein-poor diet) for 6 to 12 weeks and used insulin therapy. Nothing comparable had been done by any other means, nor has it been since (including Virta Health patients, for whom insulin use is discouraged – the Virta people also have no understanding of the basic research and endocrinology). And although I knew Walmart sold insulin for $25 per vial I did not know it was over-the-counter at that time. So I considered Bernstein my only hope for “beta-cell recovery”.
I got a lot out of seeing Bernstein – just not quite what I originally had expected. He commented, dozens and dozens of times, about how unusually “stable” my diabetes was. By that, he meant how stable my BG could be with insulin therapy. But he never had the curiosity to figure out why. I did.
Stefan Fajans was one of fewer than a half dozen of the first and foremost researchers of monogenic diabetes. Late in his career he wrote, in one of his published papers, that he felt HNF1-alpha diabetes likely is NOT intrinsically progressive. I know, from my own case, that he was right on the money with this conclusion. Unfortunately the standard therapy for all HNF-type diabetics is sulfonylurea. One big reason is that HNF-type diabetics require only 20% as large a dose to achieve the same insulin-secretagogue/hypoglycemic effect as a T2D (with 100% dose). Sulfonylureas slowly kill beta cells, inducing higher rates of apoptosis (which is more or less the same thing as in T2DM IMO – both the drug and the condition induce pathophysiological levels of ROS stress that cannot be kept pace with by cellular repair). Indeed, in T2DM insulin dependence generally takes only 3 to 5 years, whereas HNF1-alpha diabetics can go 5 to as much as 30 years before becoming insulin-dependent. Bernstein is correct about sulfonylureas I am convinced, and I know of evidence that he does not know of.
If I were a HNF-type diabetic (oh … I guess I am) I would care about this. If I had been LUCKY enough to be treated by one of the monogenic diabetes researchers I would have been put on sulfonylurea (had I not known what I do know, because I draw my own conclusions from the literature and I manage my own condition). Maybe not a disaster, but certainly diabetes is easier to manage with more, rather than less, beta-cell function.
Now in case the reader has not already recognized my final point, it seemed the ultimate irony to me that I had justified seeing Bernstein because I wanted access to insulin therapy in order to generate “beta-cell recovery” (words that Bernstein himself uttered to me once or twice early on). And once I had really figured everything out correctly, I realized that there was no such thing for me. I had never had any beta-cell loss, and hence could not hope for any recovery. I just have tiny beta cells with highly underexpressed insulin genes/proteins. The mutation is autosomal/dominant in a homeobox (transcription-factor gene).
So Bernstein might not care what kind of diabetic I am, but I sure do and it matters. It matters a lot, and it has a direct effect upon what is a useful management strategy and what is not. And upon what is useful to monitor with bloodwork and so forth.
So that is my diatribe on why patients can achieve a heck of a lot by doing their own homework and not relying upon the medical industry for what it does not do or provide best. And often what the industry pushes is harmful or at least not at all optimal for the patient. I don’t blame industry – these are people trying to make a living and protect their means of livelihood – for anything they might not optimize for a patient. That is not industry’s “job”. It is the patient’s.
P.S. Getting back to practical solutions as opposed to theory, probably the insulin shortages will dissipate and supply will get back to normal. But maybe not.
Insulin therapy requires careful empirical optimization to be reliable. I admittedly can get away with less precision than a T1D, but I still try to be very careful.
If the supply problem with analogs continues to get worse I think my suggestions can be useful and usable for many. Otherwise it is academic.
Jen, I have certainly heard others make the same comment about NPH generating erratic hypo’s previously. Possibly the protamine molecule introduces variable suppression and latency of insulin flux from adipose in some. There is also a known immunological response that can rarely be anaphylactic. Possibly subclinical immunological responses are involved in the lack of reliability for some diabetics.
So that sounds like a real problem.
Had to look up Fiasp – Novolog plus vit B3?
I guess it comes down to low-carb vs. high-carb meals. If there is enough meal carb to dictate the bolus injection requirements of both size (# units) and time profile then I call it “high-carb” for the diabetic. For low-carb I would argue that a half hour response time is good enough because protein really takes a long time to get into the portal vein in the form of AAs. Even forty minutes (the supplier’s figure measured by whatever means) probably would not result in too much hyperglycemia for an injection taken just before start of meal, and if so then a bit of lead time should be added.
So as with most in life, it is a tradeoff. I myself want to reverse my diabetic complications, and carb’s are of no value to me. I am antisocial and that helps
Under Bernstein’s regimen he had me injecting 3/4 of an hour before meals, but we were just fiddling with tiny variations in the BG log as he admitted. Since then I did the experiment he advised in his book (ironically we did not do that while he was involved) and I just inject at the same time as I start my meal. I get better results now than I ever did under his care.
Also, I should admit that HNF-type diabetics are considered to have unusually HIGH insulin sensitivity by those specialist researchers that study the condition. That is, higher than in T1Ds and nondiabetics. The mutations appear to have originated in Nordic lands/peoples, where there is no vegetation. That makes some sense, from an evolutionary point of view. There would be much less need for insulin and there would similarly be a selective advantage to higher insulin sensitivity to make use of the smaller amounts of available dietary and blood glucose.
And indeed I personally have bloodwork that is consistent with high insulin sensitivity.
With regard to hypo’s it was very interesting for me to observe how Bernstein himself actually manages his own BG. Since I saw him for three full days (his standard practice for new patients, when possible) I got to observe his regimen thoroughly. His description had previously not made complete sense – I could not believe that he could so accurately peg his BG as he claimed.
I think that reliability of an insulin regimen is a bit better intrinsically for a diabetic who manufactures negligible endogenous hormone. But Bernstein has a trick that I have never heard him really describe or mention. He overdoses a bit on the injections, on average. Then he brings himself up with fast-acting dextrose (he drinks a liquid solution) every hour after measuring. He needed hourly glucose more times than not when I was with him. He was never over target, usually under target, and occasionally close enough not to take sugar.
He gets his glucose strips for free of course. I don’t and I pay 100% out of pocket (no insurance coverage). And I buy the only strip (Abbott Labs Freestyle Lite) that Bernstein finds acceptable in accuracy in the normal BG range, which is also just about the most expensive on the market unsurprisingly.
I find his tradeoffs extreme – probably others find my tradeoffs extreme. I do pretty well spot-checking now – I am rarely very far off target. I probably use a couple strips a day on average.
With the advent of CGMs I think that it is now much more practical to emulate Bernstein. And he himself uses one now, whereas I saw him only 5 and 1/2 years ago before he did. I never know for sure if someone uses a CGM unless this is stated, but I think that most insurances cover them for type 1s now. I think that is a potential game-changer for hypo’s. So that is just another insulin-regimen idea – not my own.
Where are there any insulin shortages??? I have not seen any. I buy all my insulin in Canada and recently Quebec has stopped selling more than an emergency supply to US residents. That made very little difference for me as it just meant that I need to go over 1 province and order Humalog there. It is a zero sum game as all Humalog, as far as I know for North America comes out of the Lilly factories in Puerto Rico or Indianapolis. I talked with individuals in Quebec and they can buy all the Humalog they want in Quebec and are told there are no shortages there.
This does not appear to be a shortage issue, at least not at this time.
Well, I might be getting things a bit confused, but there has been a barrage of stories in the mainstream press during the last year or so, like this one:
The gist of the stories is that a lot of diabetics cannot access insulin, whether because of lack of medical insurance or supply shortages or other reasons. At least in places such as Puerto Rico, due to acts of God, there have been shortages. I think I have read of shortages within the continental US too, in rural areas. And I think I recall reading of shortages, at least for a short time, due to factory disruptions in PR. And so I was thinking of a seemingly large number of such stories that I have read.
I guess in the case of Quebec, which is the 2nd most populous province in Canada at ~8 million but still about the same size as just my state of Massachusetts, they might just not want to take on the inventory/sales fluctuations that they might see from across the border.
In any case, these insulin analogs are expensive – I paid more than 10 times as much for each 1000U vial of detemir and aspart as I pay for Regular and NPH. And I had insurance then, and have insurance now. I just have no coverage because I do not have one of the common forms of diabetes. Actuarial and formulary work is just not even done for my form of diabetes – I am treated just like a nondiabetic by medical insurance. So my tradeoffs are different from those T1Ds with insurance, but not from those without.
To add to my probable mixing up of things, diabetes is one of my less serious medical conditions. Two are purely genetic and the other is congenital and partly genetic and related to the HNF1-alpha mutations. The latter is MSK (medullary sponge kidney) with severe hypocitraturia (below that which the instrumentation can detect/measure) – a pretty extreme case in both kidneys that generates a constant flow of calcium phosphate stones that in turn cause little renal and urinary-tract lesions and hence constant hematuria and consequent loss of iron. One reason I eat a lot of liver. I also have to be very careful with diet in order to avoid larger calcium oxalate stones that are seeded by the calcium phosphate stones. I cannot tolerate the only prescription therapy prescribed by urologists for the condition because of my more serious condition – CVID, which is a primary/polygenic immunodeficiency (PID).
PIDs can be treated with only one intervention – other people’s antibodies. I started infusing weekly only a year ago at age 61, which is very old for this condition. And there HAS been a supply shortage crisis for the Ig (i.e. the blood product providing the donor’s antibodies, aka immunoglobulin, aka gammaglobulin). That also has made a lot of news in the last year or two since the problems have arisen.
I self-diagnosed the CVID in early 2011. I self-diagnosed the diabetes in 2010. The MSK is the only one that was diagnosed by a physician, using contrast CT imaging, and the last one to be diagnosed. I started generating kidney stones that caused ureter blockage only after I started using insulin, which increases renal blood flow rate by a factor of many in the case of bolus injections. That made the difference, evidently.
Anyway, I digress. But my diabetes is the easiest of my three conditions to manage. I manage it unconventionally (otherwise I would use oral secretagogue and kill off my beta cells slowly).
The CVID is the most difficult to manage. I have virtually no B-cell function at all (not to be confused with beta cells). In other words, I cannot manufacture my own antibodies in adequate number or selectivity (for antigens). One of the many consequences is that I have gradually become unable to eat plant foods, more and more as I age. In recent years I have become unable to eat virtually anything anymore, and so I now eat only animal-sourced foods. Otherwise I generate explosive inflammation, usually with bleeding, which would kill me in pretty short order (a few years) unless I avoid the plant foods. Death would come by starvation due to loss of intestinal tissue required for nutrient absorption – so-called “granulomatous” disease. This kills many with my condition, typically by early or mid forties. Nice, eh?
Anyway, all of my conditions are outliers (rare) and most of my experience with physicians and the like has been obstructive and unhelpful. All of the people I have met with rare medical conditions have had the same experience, and have typically self-diagnosed and mostly self-managed. For many of these conditions there is NO known treatment whatsoever, so I am lucky. Please forgive me for being more than skeptical of standard medical guidance and “solutions”.
I do think that the insulin industry is one of the best of the medication/pharmaceutical sectors, in terms of product value and efficacy. But profits are still a factor. Insulins such as ultralente have been discontinued purely for commercial reasons, with clearcut deleterious consequences for T1Ds. Ultralente was a human insulin, and could be easily diluted, and so forth. Nothing as effective has replaced it to this day.
Anyway, I should be glad for all of the diabetics using high-profit products from Novo Nordisk and the others. That makes it easier for these companies to provide me with cheap human insulin.
I did that for years. Ended up with ambulance rides for two serious lows. One while I was sleeping (convulsing), the second when I passed out at a business dinner. I have no doubt what you describe works. I’m living proof. Go back another few years and I survived on beef and pork-based insulin/NPH. I would return to them only as a last resort. That would happen if I had no insurance, couldn’t source from a country with reasonable prices, and didn’t have the financial means to pay out of pocket in the US.
Diabetes control technology (medicine and hardware) marches on. Each iteration is better than the last. If you’re fortunate enough to access them, you’ll be all the better for it.
I have been a type 1 diabetic for 27 years. I was diagnosed by going into a coma with a BG of over a 1,000mg/dl and I got to that number within a few days of showing symptoms. I have 3pmol/L of measurable c-peptide and let me tell you that not having any endogenous insulin production is the pits.
I was diagnosed a little too late to be on animal insulins but I was on NPH for over a decade before Lantus was approved for children. NPH for those like me who have unpredictable absorption is like playing Russian roulette. I had to sleep in my moms bed, I routinely passed out at school since the insulin would peak when it wasn’t supposed to and Dr.s tried to diagnose me with epilepsy I had so many seizures.
On the other hand R is a trusted standby for me, 1 unit will bring me down about 30mg/dl but I use it about an hour before meals to help cover the protein. I also use Afrezza though. I have tried every diet you can think of including cutting out all carbs or vegan diets and every single one will initially help but then my control will gradually go back to where it was before starting the diet. So I mostly eat what makes me happy and healthy and take whatever I need for it. My control isn’t great but not from lack of knowledge or trying. Insulins also for the most part seem to initially help with my control but then I appear to develop a resistance to something in them and have to turn my regimen upside down.
I am convinced that I have an underlying condition at this point but so far no diagnosis. I could survive off of R if I had to but Afrezza really helps to correct those times when the R doesn’t absorb well and of course for the carbs I do eat. I think comparing monogenic diabetes to type 1 is like comparing apples to oranges. What works for you is very difficult to make work for the rest of us. Your beta cells do work perfectly but if I understand you correctly they are just too small to hold diabetic symptoms completely at bay. My beta cells were killed off by my confused immune system when I was a toddler.
It is absolutely possible to survive off of the older insulins but why should we have to? Humalog and R used to be almost the same price, the rise started in 2008 where one day I went to the pharmacy to pick up my prescription expecting to pay about $40 as I had been for years and all of a sudden it was $80. This is greed Mac pure and simple. No drug or commodity doubles in price over night and in the next few years it would jump anywhere from 15-20% every few months for no reason. Eli Lily and Sanofi haven’t developed a new insulin in decades, they haven’t built brand new factories or payed their workers more than the average. The top dogs however are getting salaries in the millions and there has been very little put toward so called “research”. Please don’t defend the business practices of slime balls.
Are you sure this is the culprit? Are the top dogs really proportionally earning any higher compensation today at today’s insulin prices than they were when your insulin was at $40? I hear these wild accusations often made and they make a great talking point especially on the part of the media and politicians but is there any truth to them. These are public companies after all and C-suite salaries and compensation are public record. I have not seen any comparisons between insulin prices and “top dog” compensation adjusted for inflation.
The reason I seriously question your top dog premise is because these same top dogs from these same companies from the same factories are selling their identical insulin to other countries such as Canada where the insulin is available at retail for 90% less than in the US. This would lead me to believe that the issue is not top dog greed at the manufacturing level, but all the insurance, pbm and other fingers that are required in the distribution of insulin between the manufacturer and the consumer in the US.
I’m with you and @Jen there, having had the same experience. Now that I have a CGM I’m sure I could manage much better than back in the dark old days if that gun was held to my head, but just the thought of that stuff elicits a visceral response in me that’s hard to get past.
This topic has strayed off topic but finding where to split it into a second topic is difficult. @CJ114 you are the OP, do you wish for the topic to be split? If this topic were to be split at which point. @Firenza, @CJ114
I have no objections for the moderators to slice and dice this thread any way they see fit to provide forum members the best experience. Go at it!!!
My eyes glazed over at the amount of technical detail that Mac is sharing. I didn’t think this was a place for that much scientific detail but what do I know. To say “TLDNR” is an understatement! Merry Christmas everyone!
Oh, and IMO Regular blows. The only insulin worse IMO is NPH.
Each T1 or T2 has to find what works for them. For me, Novolog took 45-60 minutes to start working. Novolog also stayed around too long, at least 4 hours and linear decline in Medtronics pump was a poor model. Short trial with Humalog (requirement before getting FIASP) was as bad or worse. FIASP starts affecting my BG in 20-30 minutes. Active insulin time is about 2.75 hours and actually matches linear assumption in my Medtronics pump fairly well. Overall, FIASP lowered HbA1C while decreasing hypo and hyper episodes.
Pretty much the same for me, particularly regarding the AIT and shorter “tail.” The published graphs are all very well, but not to be confused with how it behaves in an actual individual metabolism.