That makes more sense !!
I’m an accountant by trade. Accounting is driven by the basest of math between debits and credits. That’s how George44 is viewing diabetes and diabetes treatments.
Like you point out, [quote=“David49, post:19, topic:62569”] the pancreas is an incredibly complicated organ [/quote], and to look at it as a simple debit / credit transaction is far too simplistic.
Brilliant !!
Spot on !!
Precisely this. One of the things we often don’t really think about is why we have five auto-antibody tests for Type 1 (there are actually more than that, but they don’t get used at the clinical level). Antibodies are indicative of the immune system being primed to target human cells or structures, and having different antibodies means that different cells and structures are targeted. So, two “Type 1 diabetics” with different antibody profiles don’t actually have the same disorder from a biochemical standpoint. The causes are different, even if their presentation (and treatment) are similar.
This is likely why some T1 cases are “rapid onset” and diagnosed during DKA, others are very slow onset LADA presentations in adulthood, some are caught in “pre-symptomatic” stages, etc. The “mystery” Type 1 (Type 1b, idiopathic DM, DKA-prone T2) varieties are characterized by presentations and disease progression similar to Type 1 without any positive antibody results. What does this suggest? That there are other autoimmune processes affecting the pancreas that we don’t have tests (or biochemical knowledge) to assess.
Type 2 is likely even more complicated than Type 1, from what academic research is suggesting. Some researchers now believe T2 is also autoimmune in nature. More than forty different gene sequences have been associated with susceptibility to T2, indicating that there are likely at least forty different underlying causes of T2. How do you treat a disease you don’t understand the causes of? You treat symptoms or “cascade points.” Blood glucose is the easiest thing to target in DM management for both T1 and T2 (and MODY and MIDD), but the manner in which BG is managed is really different from patient to patient.
tl;dr: It’s complicated. Incidentally, I wish all science worked on the basic math principles of accounting 
It would make my actual job a lot easier, even if it would likely be less interesting.
This is interesting stuff. It sounds like diabetes and related treatments are every bit as complicated as cancer and cancer treatment.
David and Micheal - thank you for the exchange of ideas. By trade I am an engineer and I see the body as a complex machine composed of interacting subsystems. Treating diabetes is actually a flow control problem. This is the approach “Engineer” Bernstein takes and also the approach Al Mann took when he developed the insulin pump. For “tools” Bernstein had a meter, glucose absorption rates of food and the speed of insulin, Mann had a computerized pump and sensors and again insulin speed. What both struggled with was the flow of glucose was out pacing the speed the insulins they were using to counter-act the BG spike. In other words they were limited by the insulin which was too damn slow.
With real time sensors and insulin which reacts like pancreatic secreted insulin addressing the flow control is not that complicate but needs to be tuned on an individual basis called titration. We have been taking a similar approach with IV insulin in hospitals for years monitoring real time through real time monitoring. You see it doesn’t really matter what caused diabetes the end effect is damage to the pancreas has occurred and the body is not producing enough insulin for body signalling and glucose utilization.
The terms Type 1 and Type 2 are historical terms putting diabetics into two categories; those which needed to be put on insulin today or they will die; and those that can wait for some period of time before they need to be put on insulin. Prior to the 1960’s T2’s were seldom treated except with diet and exercise. Insulin was viewed as too dangerous and not worth the risk of hypoglycemia and killing the patient. The first widely used non-insulin sulfonylureas was Orinase introduced in the U.S. in the late 1950’s. It really was not until Orinase and the potential for HUGE money by Big Pharma that a “T2” market was born.
I have so many studies on early insulin intervention they would fill a 4 draw file cabinet. Some of them date back to the 1950’s and the last was about 6 months ago. They all basically say the same thing. There are huge benefits for the PWD with early insulin intervention. In other words skip the “Step” program and put them on insulin day one. However, there is much less money in this for Big Pharma. The T2 market is huge at least $30B and probably heading to $60B.
drug-dev.com/Main/Back-Issues/Global-Type-2-Diabetes-Market-Set-to-Almost-Double-1140.aspx
No Big Pharma wants this disrupted. In fact they will rush a product like trulicity to market hoping to grab the money from Januvia Byetta and Victoza if they lose their lawsuit and they get pulled from the market. That said truth is its all about the money with Big Pharma so PWD beware of the product you are taking. And, the fact is most doctors only know what the sales rep has told them. Diabetes treatment has changed so much in the last 5 years because of the real time sensors - CGM, cloud connection and a fast insulin which can mimic the pancreas. In fact,now I can sit in my office an watch real time a PWD arcoss the world and see their glucose profile thanks to Dexcom and the cloud. Thats only been available for a few years way after your doctor went to school.
As I mentioned, diabetes is a flow control problem. You will hear terms like “closed loop” when they are talking about the Artificial Pancreas. Now, the one thing all diabetics have in common is they are not producing enough insulin, regardless of the cause. The question is to what degree are they producing insulin to meet their glucose infusion needs? The answer to that is unique to the patient and can be measured with our real time sensors (CGMs) during a glucose test. The second question is are their beta cells still under attack from their immune system and if so how aggressively. The answer to that is answered with many different lab tests combined by ongoing monitoring. Again this will vary from patient to patient. Now we can call some people T1, and some T1.5 and some T2 and LADA and some MODY and some MODY-2 and even MODY-3 and a few more names. Whatever the cause and whether or not they have active immune system activity none of the PWDs are making enough insulin but some are making more than others.
We see people all the time get on this forum and say I was a T2 but now they say I am a T1. Or I was a T1 but then my BG was perfect and then a T1 again in the early stages of the immune system attack.
We can even debate whether “T2” is the result of insulin resistance as a result of diet and exercise and being obese. Now its my theory which I have no hard studies that almost all T2 is the result of some type of attack on the beta cells and the attack is mild enough that there is no trace in the immune system by the time testing is done for anti-bodies. Coupled with the insulin resistance the body can not recover without help. What we do know is T2s share genetic traits by gene type so we know there are more than a dozen different variations of T2 but again it does not matter unless we are doing research for a cure. I am not. I am addressing the flow control problem.
However, what I will say is we have a lot of obese people who do not have diabetes and when autopsies are performed on their pancreas they have grown big clumps of beta cells. We also have identical twins and they don’t both always develop diabetes. So, clearly while genetics and insulin resistance play a role they are not the root cause of what attacked the pancreas and damaged the beta cells.
The problem in addressing the flow control problem is mimicking the pancreas but the insulin action with available “insulins” has always been TOO damn slow. Its all about how fast injected insulin will start to work and then how fast it will stop working. If you have a “tool” (insulin) which mimics natural pancreatic insulin action, you have the “Holy Grail” in diabetes treatment. You may not have cured it but now you can mimic natural insulin secretion and action.
Now Micheal said " BG readings have dropped dramatically and never goes over 125". If you are getting postprandial BG readings never going over 125 with Trulicity thats awesome. You are seeing non-diabetic numbers. However if that 125 is your fasting BG reading thats not great. What they did do in the studies is combined Trulicity with insulin - Lantus and usually quote those results saying significantly more people treated with Trulicity 1.5 mg plus insulin glargine achieved an A1C of less than 7 percent (69.3 percent) compared to placebo with insulin glargine (35.1 percent).
OK, what does Lilly say - use Trulicity with insulin for better results. We know the issue T2s have is not fasting insulin production by the pancreas but rather the meal time spikes so we know Lantus is not the proper tool. The proper tool is a meal time insulin and the best is the one which mimics the pancreas. Its really all about using the correct tool for the job. However, I bet if you use afrezza and properly dose and keep you meal time spike under 140 you won’t need trulicity for BG control. In fact if all my early insulin studies are correct, early diagnosed T2 will see a regression in their T2 and will probably be able to control with no meds for years. I bet if the trial was done as trulicity/Lantus on one arm and only afrezza on the other, afrezza properly titrated would win hands down and trulicity would never have gotten approved.
Now, if your goal is weight loss and trulicity seems to help thats great but are there other methods which would provide similar or better weight-loss results without the risk? Whats clear is in the department of T2 glucose control and specifically the issue a T2 has which is meal time spikes trulicity has little effect. As Lilly says themselves after 28 weeks of treatment, Trulicity 1.5 mg plus insulin glargine significantly reduced A1C from baseline (1.44 percent) compared to placebo with insulin glargine (0.67 percent). Yes, less than 1% from the placebo is what Lilly says. https://investor.lilly.com/releasedetail.cfm?ReleaseID=975363 Thats not very good.
Interesting that you mention Berstein. In his book, he fully recognizes the severity of carb cravings when he describes this cycle of weight gain, insulin resistance, increased BG, increased insulin, carb cravings, and back to weight gain.
Bernstein, himself, recommends GLP-1 Agonists to fight carb cravings in T1 D and get things back on track.
I have no long-term plans for using Trulicity. The side-effects are just too harsh and the deleterious affect on quality of life is just too significant.
That said, I do plan on using it to break this negative cycle I was riding - which also has a deleterious affect on quality of life that is just too significant.
This is, I think, where we are getting a bit confused in the way we’re discussing this. I really do believe almost everything you say about Afrezza and insulin speeds for those diabetics who are insulin dependent. And I also agree that there are likely diabetics (maybe lots of diabetics) who should be on insulin and aren’t. But there really are a lot of Type 2s, and even a handful of Type 1s, who for various reasons aren’t taking insulin and are still maintaining tight control. There are also diabetics of all types for whom insulin resistance is a serious problem, regardless of the chicken or egg question of why the patient is insulin resistant.
This is where certain kinds of oral medications make a lot of sense for some diabetics. For some Type 2s who produce plenty of endogenous insulin, but have high insulin resistance (or an overactive and unhelpful liver), a drug like Metformin is absolutely amazing at increasing insulin sensitivity with only very minor side effects (GI troubles). I happen to be in the category of Type 1s (only because my condition was caught really freaking early and probably just after the autoimmune attack started) who also benefit from Metformin: not because I’m insulin resistant, but rather because Metformin also tends to reduce gluconeogenesis and limit the amount of glucose the liver can dump into the bloodstream. I’m sure that one day I’ll be on insulin. In many ways, I wish I had access to Afrezza or a similarly fast-acting insulin now. But I don’t.
So, for now, diet, exercise, and Metformin happen to be the best tools I have available to control my BG. For some Type 2s (not all, and oftentimes not forever), especially those on a low-carb diet, there really isn’t any need or room to use insulin now. Metformin, and other orals which have different kinds of actions, can definitely be useful in those circumstances. The class of drugs you seem to be fixated on, which encourage the release of insulin by the body’s functioning beta cells, are not the only oral medications available to diabetics. It doesn’t make any sense to throw the baby out with the bathwater: some oral medications can serve useful purposes for many diabetics (increasing insulin sensitivity; reducing hunger; encouraging fat loss). If the body needs insulin, then clearly matching a basal with the fastest-acting bolus available makes good sense.
David - sorry to hear you have no access to any meal time insulin. If you have access to a basal you may want to consider this as it will off load the beta cells of some of the work to potentially allow beta cell regeneration. You will never get that resting time with metformin and why most T2’s progress. I wish you all the best.
Micheal - I have not seen a review from Bernstein on afrezza. As I mentioned the problem he was trying to solve was managing the BG rise because the insulin was too damn slow. With an insulin which mimics natural profile the problem is solved. It obsoletes his approach including his GLP-1 recommendation. You no longer have to highly restrict the carbs. The insulin is fast enough to not only deal with the meal time rise but it will actually blunt the spike. Here is a presentation where Al Mann says afrezza obsoletes the pump around the 26:50 minute mark. However the more interesting discussion starts around 33 minute mark. Now, this is coming from the guy who invented and made a fortune with the pumps. I think he says $4B.
enjoy - Alfred E. Mann 2010 Johns Hopkins University CBID Design Day Keynote - YouTube
With pre-bolus the problem is also solved. Time it right for the particular food and there is no spike.
Perhaps not as convenient as some alternatives but certainly an option.
You’re really missing the point, here. I’m not Type 2. I will progress, there is no doubt. But the point of Metformin isn’t to avoid insulin, or even to bring down BG. The point of Metformin is to modify how much the liver dumps glucose into the bloodstream during Dawn Phenomenon or exercise spikes. It also increases insulin sensitivity.
I don’t have access to basal or mealtime insulin, and that’s completely besides the point. Although I could certainly benefit from mealtime insulin, in particular, not every diabetic problem comes down to insulin. Seriously, do you not understand insulin resistance, sensitivity, and other factors involved in people’s disorders? Just increasing insulin, or just getting the timing right, does not solve all diabetics’ problems. Insulin resistance isn’t a function of the timing of insulin. This is why many Type 2s produce more insulin than a normal person does: their problem is not lack of insulin. It may END UP as a problem of lack of insulin. The problem in that case is too much insulin.
Anyways, you clearly have your mind made up on Afrezza somehow being the magical answer to all diabetic’s problems. Man, I really wish I had a doctor that would prescribe it to me. But I also know that even when I do have access to Afrezza, it will not actually “solve all my problems.” The body is a complex system, and it’s a hell of a lot more complicated than merely “carbs in and insulin to balance,” regardless of speed of action.
Tim - not really. Pre-bolusing with a standard RAA is not the same. Look at the presentation above and the charts being displayed. The graph showing the tall peek is what is needed to signal the liver to turn off glucose production and is needed in the short time to pound the spike and blunt it. Thats what phase one pancreatic insulin release looks like. Notice the grey line, you’re getting a rolling hill not the needed first phase release. Its a big deal to keep the liver and pancreas in sync.
Now, the rolling hill if you can time it right is so much better than any T2 med, way better. But again not nearly as good as mimicking phase one release.
@George44 - I would certainly agree it would not be the same. Not saying better or worse but certainly not the same.
My only point is “pre-bolus” is an option and not one that should be ignored or pretend does not exist.
Nancy there is a coupon for Victoza. 25$ copay for up to two years. I am starting it. I had a coupon for Trulicity too. The Trulicity worked better for me the first weeks. I have health insurance but the coupon is a much better deal. Good luck!