P.S. I see that you report testing has been done for all three recognized autoantibodies associated with insulin secretion by beta cells. You mention no results, but I presume that all were negative. If not, you have a T1D child and MDs would be highly irresponsible not to put her immediately on insulin therapy.
Sorry for my omission to read your post of Aug. 23 earlier today.
I think that one other responder/comment-poster mentioned the possibility of negative a/b test results with T1DM. I have also heard of this – I think it is unusual but do not know the observed stat’s/probabilities off top-of-head. But this is one reason that I suggested testing at least twice, with some significant time interval in between. I would agree with the other responder that you should not yet rule out T1DM by any means.
If your daughter has T1DM but is in an episodic on/off stage/phase of autoimmune activity, that would be highly consistent with her apparently slow rate of progressivity/decline, especially for a T1D at her early age. And highly hopeful for her/you to rescue from mature T1DM and clinical insulin dependence as well. If it were I, I would immediately adopt a very low-carb diet as a prophylactic measure. Just a suggestion.
That said, one of the forms of MODY is a possibility, and each case (even for the same type) is unique because the individual combination of mutated SNPs within the single underlying gene are different in every case or family or familial line of inheritance.
While reiterating that MODY diagnosis is much less urgent before fully ruling out T1DM in my opinion, some cases and acute-insulin response-deficient (all but MODY-2 to my knowledge) forms of MODY do indeed look like not-yet fully-mature T1DM phenotypically. Very much so. And for a knowledgeable observer, always much more so than like T2DM – always. Your daughter MIGHT have started out, congenitally, with little more than 20% of beta-cell function due to a form of MODY. This is not unheard of. That would be good news, relative to T1DM.
She has lost insulin granulation, at least recently and episodically, already. So independent of diagnosis of form of diabetes, it is fairly important to now regulate her BG with something, and in my opinion it should be insulin (including for any T2D, and definitely for MODY or T1DM). Regardless of what any MD, almost none of which understand the biology to any significant degree, might opine or advise. For absolutely fundamental reasons. Which I can extensively elaborate upon. And for any form of diabetes it is even more important to minimize dietary carb’s and portal glucose (these two are inseparable anyway) along with subcutaneous insulin therapy. But ESPECIALLY for early or immature T1DM.
Worth testing for MODY diabetes.
Meglitinides: For anyone who might be interested, and especially those with MODY (excepting MODY-2), there is a newer and much less common form of oral insulin secretagogue than the broad class of sulfonylureas. I do believe that the clinical research specifically on HNF forms of monogenic diabetes (MODY) clearly confirms that sulfonylureas overstress beta cells much like modern urban diet in pre-T2DM and overt T2DM does. In somewhat over half of the general population there is a beta-cell genome-based capacity to increase the population of beta cells in response to dietary stress (of too much carbohydrate, quite simply) in response. These individuals will remain in the pre-diabetic state, which is highly unhealthy, for life (without correction of diet) but never develop overt T2DM. They will never enter the so-called “decompensation” phase of developing/progressing T2DM. The others will, and unless dietary intervention is applied soon enough they will become overt T2Ds.
For ANY of the three HNF forms of MODY, the required dose/titration of any oral secretagogue (for equivalent efficacy) is only ~20% of that for a T2D. Indeed, this is a cheap-and-dirty clinical diagnosis method for highly likely HNF MODY, if applied experimentally.
And so, with sulfonylureas the rate of apoptotic loss of beta cells and of cell function might be only roughly one fifth of that for T2DM, or substantially lower (high degree of linearity of dose/response is not likely). Generally a T2D using sulfonylureas will advance to full insulin dependence within five years or less. I do believe that any non-diabetic would also lose beta cells and cell function at the same rate as would a diabetic, for a given oral drug regimen.
Meglitinides are a newer type of oral insulin secretagogue, and their mechanism of action is much more “prandially-dependent”. Which is a good thing, and more physiological and less pharmaceutical. Sulfonylureas have absolutely no prandial dependence of action or potency.
For any MODY patient or even T2DM patient (short of insulin dependence) who refuses to consider insulin therapy, meglitinides MIGHT not cause much or any accelerated apoptosis/loss of beta cells. I think that the jury is still out on that, but clearly the evidence so far indicates far less long-term damage than with ANY sulfonylurea over a time interval of more than a decade. Of course, amongst the scarce number of research clinicians who treat MODY, sulfonylurea is the standard of care. NOONE should EVER take any sulfonylurea – none. They all reliably accelerate apoptosis to abnormally high rates, at any clinical dosage including that for MODY patients.
Luis3, neonatal diabetes mellitus (NDM) is often considered a monogenic form, but in my opinion should be clearly distinguished as NDM rather than any other form of MODY.
NDM is, quite commonly, transitory. That is, NDM does not always persist for life and often goes away in later youth. There are some well-understood and most common forms and some idiopathic forms I believe.
Almost exactly the same clinical researchers as have studied longer-recognized forms of MODY also study neonatal diabetes. It is almost an identical set of researchers. Hence, one reason for the association of NDM with MODY. The “mature onset” and “neonatal” seem completely non-overlapping, by definition, to me. Despite the fact that one of the foremost and earliest researchers (the late Stefan Fajans) of HNF1-alpha diabetes (MODY-3) opined, late in his career, that it was/is intrinsically non-progressive/stable. And my case certainly is that. I doubt that any other case is any different, due to the purely genetic underpinning and independent of additional acquired dietary or prescription-drug (i.e. sulfonylurea) insults. And from what I have read of NDM I find stark fundamental differences between MODY and NDM, from the biological and genetic and phenotypic points of view. I think MODY is all monogenic by definition. And some common forms of NDM are considered to be also, but I am not sure all are known or likely to be.
Anyway, it seems unlikely that the original post-er (thread originator) whose daughter has recently exhibited clinically overt diabetes for the first time at age seven has any form of NDM, to my mind anyway. It is usually quite evident at birth. And of course, congenital or neonatal diabetes is NEVER T1DM – the adaptive humoral response is fully undeveloped at this stage, and hence quite incapable of generating antibodies to insulin-secretion associated antigens yet. By age seven, quite the contrary.
Your reference/citation of the SEARCH study looks a bit interesting. I briefly scanned introduction and abstract. The broad youth cohort was defined as younger than 20 years of age. Teenage diagnosis of common forms of MODY, like mine, have long been recognized as not uncommon. Age seven, however, seems quite rare or absent in the much older clinical cohort studies that I have read thoroughly, based upon recollection from many years ago.
Anyway, I know little of NDM – that is a form of diabetes that I have not studied much at all. And I have little interest. The two common acquired forms and the more common MODY types I am very well familiar with, in depth and breadth. I did exaggerate in claiming broad understanding of ALL forms.
Use of the term “pediatric” up to the age of 20 seems inappropriate to me. Maybe up to age 10. But possibly I am quibbling over semantics. I would be curious as to the age distribution within the SEARCH cohort ID’d with one of the two HNF types of MODY. The MODY-2 is of total disinterest to me – there is absolutely no deficiency of acute insulin response in this unique form of MODY, and hence no complications and no appropriate medical treatment whatsoever. It is a completely benign condition. So I find inclusion of MODY-2 very inappropriate and misleading/distorting in this study – a personal opinion. I would want to throw out all of the MODY-2 diagnosed cases from the cohort data, and include only the remaining two HNF types. And MODY-2 is one of the most common forms of MODY. So very likely a large percentage of the ID’d MODY cases in the young cohort, and certainly irrelevant to conventionally clinically overt diabetes (i.e. loss of insulin granulation in beta cells, with immediately ensuing polydipsia and/or polyuria symptoms) at age seven or at any age whatsoever. Geez …
So I don’t like the study design from the get-go. There is an awful lot of crap in the clinical research. Maybe there is something that can be discerned from the full data set in SEARCH. Usually not made publicly available anyway, much less heavily relied upon in the published paper(s) and conclusions/hypotheses generated from a cohort study.
If the principal “investigators” in a clinical study cannot do a decent job of either design or analysis, I tend to be unmotivated to put much effort into such myself. They get salaries paid out of the underlying grant money, and I do not. Rather, I have different motivations.
P.S. I might add, to my last post regarding the antibody results being “high” as far as I am concerned, that an MD will be going by different guidelines than would I as a patient, or for a patient solely in that patient’s interests.
Without looking up the standard clinical guidelines with respect to youth/juvenile T1DM diagnosis, which I could easily do (but so can anyone else), I would expect that the MD would consider two of three readings right at the upper boundary of a test lab’s “normal range” to be equivocal or at least not urgent, with justification to “wait and watch” (or whatever other silly clinical phrase might be applied).
And such is what the thread originator reported in her initial post.
From everything that Razorbacks1113 reports, it would be my guess that her daughter is in an episodic phase of autoimmunity (to beta cells) that is characterized by waxing and waning, or even off and on, which would not be unusual for a not-yet insulin dependent T1DM with still more than 5% of beta-cell function remaining. In fact, par for the course. MDs do not observe much of anything before 100% insulin dependence occurs. Those are the guidelines, and that is the attitude. The former is motivated largely by legal protections for the MDs (fair enough, especially in USA), and the latter is just how it is – I am not passing moral judgement but patients (and their guardians) should be well aware.
But from the case history for which observations HAVE been made, a fluctuating and episodic course of beta-cell loss due to unstable autoimmune activity is the norm. So this can be presumed, by default.
With episodic autoimmune activity, the a/b bloodwork readings will also fluctuate up and down with time.
The point is, and knowing MODY as well as I do (probably as well as anyone in the world), I do not think it likely that this is a case of MODY. Not impossible, if the girl started life with just above 20% beta-cell function to being with. Which would, all by itself, be pretty rare for the common forms of MODY. But there are so many signs of T1DM that the mother reports that I rather doubt the girl has MODY. Chances are de minimis in my own opinion.
Looks EXACTLY like T1DM at a stage where insulin dependence CAN be prevented if proper interventions are taken. And there are only two of these both necessary and sufficient, as I earlier spec’d.
One of the girl’s MDs reportedly opined (correctly, in my opinion) that this looks like “early” T1DM. My own quibble would be only with the word “early”. After 80% of all beta cells have been destroyed, I would not consider this to be early. But that is the clinical attitude, for their own benefit and protection rather than in the interests of the patient.
For an MD, a case of T1DM ceases to be early only when full insulin dependence has been “achieved”. At this point the legal/court case history is pretty definitive, and the MD is not liable for treatment with insulin therapy and not for much of anything else either. For obvious reasons. “Insulin dependent” means that the patient will die (and quickly) without insulin therapy and maybe other professional medical care. That is the legal liability key factor in court, with a long history.
So I hope you are at least reading this Razorbacks1113. I would challenge anyone on this forum to gainsay anything that I have written herein (especially in this post), and I doubt any will.
I have explained the underpinnings above. So putting the girl’s future entirely in the hands of licensed physicians (other than Bernstein and maybe a few others of whom I am unaware) will result, almost surely, in insulin dependence. That is why I said the mother must be self-reliant if she wants to follow a course to try to preserve remaining beta cells. Bernstein does not work with any insurance – all payment (including for insulin and other med’s as well as his services) must be out-of-pocket. Prohibitive for most.
For any others on this forum, as well as Razorbacks1113, who might have (now or in future) T1D children, take a lesson from what I have written herein if I am not already “preaching to the choir”.
And commercial and institutional interests (including academia, government(s), pharmaceuticals, medical (e.g. hospitals and equipment makers), and medical insurance (last but hardly least)) are ALL joined at hip in economic and means-of-making-living common interests/motivation in current industrialized societies worldwide to actively suppress anything from the knowledge of biology that is threatening to the institutional interests tied to medicine. And these are massively powerful interests – the most powerful on earth. And this is what prevails and predominates. Noone should kid himself/herself about that. To do so would be naive and foolhardy.
I have three rare medical conditions. The HNF1-alpha diabetes is not the most serious by a long shot. I self-diagnosed two of the three, and surely would still be undiagnosed for ALL three if I had not. Because the third/last to be diagnosed was only identified after I was on (self-administered/managed) insulin therapy. This is a renal condition, and insulin increases renal blood flow rate by a factor of ~4, and this led to some events that led to the diagnosis with the help of one MD. The condition was there from birth, but it never would have been detected had it not been for the insulin therapy.
I know of what I speak and write, and I would be long since dead otherwise. No thanks to the medical community, for the most part. The MDs have their uses, just like auto mechanics (and I do my own auto maintenance, except in rare circumstances, also). Relying upon their knowledge of biology/biochemistry/genetics is a fool’s mission. The key professional differentiation for MDs broadly is the license to prescribe drugs/med’s not available over the counter.
And same for medical equipment and its makers. It is good for only what it is good for, and caveat emptor.
Wow you have so much information! I don’t even know how to process it all!
P.S. I should clarify that, by saying intervention 2 without invention 1 “will not work” I did not mean to imply that the girl should not be on insulin therapy alone ASAP. She should be, regardless of the opinion of any MD who might prefer to wait and watch.
What I meant was merely that (1) is primary and necessary to stave off full insulin dependence. (2) alone can certainly reduce or prevent complications of diabetes (i.e. death of neural and microvascular and certain macrovascular tissues) due to prandial hyperglycemic transients. Which is valuable – take it from a person who went over five decades with undiagnosed diabetes and a conventional modern, urban diet (at least, with respect to carb’s which is what is most relevant to the transient hyperglycemia during portal nutrients (AAs and glucose) absorption from meal.
And for anyone with significant endogenous insulin production remaining, portal glucose CANNOT be compensated for predictably using exogenous/subcutaneous insulin – there is positive feedback (instability of endocrinological response in islets) during the prandial period. AAs (protein) CAN be compensated for reliably and predictably. Only after ALL endogenous insulin production is LOST can dietary carb’s be also compensated for. Maybe the ONLY relative advantage of losing 100% of non-diabetic beta-cell function. Hardly to be sought after – not a good tradeoff.
And noone in the world, other than myself to my knowledge, FULLY understands this biology. Including Bernstein, who completely misunderstands and incorrectly models the primary role of glucagon in ALL hepatic whole-body supply and buffering of glucose/glycogen and ketones (BHB). And he is unaware of the basic research and measurements made over the last five decades on human and canine models which clearly demonstrate what is going on endocrinologically – it is only the principles of negative and positive feedback(s) (with which many engineers will be familiar) that these researchers do NOT recognize and understand, but they have long and repeatedly recognized the stark difference in response to portal glucose between T1DM (with zero beta-cell function) and T2DM (with partial beta-cell function).
Indeed biological systems (i.e. cell-based organisms) are absolutely full of negative feedbacks, which are regulatory and confer stability. There is NEVER positive feedback in a biological system, nor a planet (earth) that has sustained life for billions of years. Both REQUIRE negative feedbacks for stability and hence persistence. An organism with positive feedbacks could not survive and reproduce. These are the fundamental laws of nature. They are ABSOLUTE – no exceptions.
Hi. Mom of a son with T1 (diagnosed at age 3, now 17). I have T1 myself as well.
I agree that it does sound like your daughter has T1. I’m sorry. It could be worse, but it could be better, ya know? The bad news is that T1 has a steep learning curve. The good news is that your daughter is going to be just fine and will be able to do anything that she could do before her diagnosis - it will just take a little more preparation and planning.
I frankly disagree with a lot of Mac2’s advice. I suspect that he has not parented a child with T1. There is much more that goes into it than the mere mechanics of beta cell preservation. Find a really good pediatric endo, and follow their advice.
Best of luck to you. 
Hi Hawkeye,
You are correct that I have not parented a child with diabetes. Although I have in-law relatives with T1D children and history of T1DM in the family going way back. And I have spent a lot of time reading about real case history of parents with children who have successfully preserved beta cells and prevented full insulin dependence in their child/children.
What I can teach of, or about, is the biology of virtually all forms of diabetes, and quite a few other conditions. The rest is subjective and personal, in terms of choices for any family or individual with T1DM.
I think that you are substituting or confusing the biology with personal choices, in saying that you “disagree”. And I did try to add caveats aplenty to my most recent posts addressed mainly to Razorback regarding the high difficulty of what she might try to do for her daughter only if she chooses to take on this type of “maverick” challenge.
Likely Razorback, presumably from Arkansas, may be simpatico with you (are you from Iowa?) based upon same circumstance and choice of monikers. And it would appear to me that she is not eager to buck the system and try to prevent her daughter from reaching the so-called honeymoon period and the thereafter (insulin dependence for life).
Your daughter having been 3 (wow … young) at time of loss of 80% of beta cells (presumably, if she was diagnosed with either polydipsia or polyuria rather than by HbA1c solely) and now 17, I would imagine that she must be fully insulin-dependent, yes? That polydipsia and polyuria, and abrupt acute dysregulation of BG, first appear after loss of ~80% of beta-cell function in ANY form of diabetes is known, by the way, from the large body of data collected by the focused islets research based mostly upon autopsied organs. Once the remaining beta-cell population is put under so much stress/demand (per cell) as occurs with only 20% of normal aggregate function, just to respond to more basal demands for non-acute, low-level insulin secretion, those cells must spend 100% of their time in continuous real-time manufacture of insulin to be secreted. Hence, there is nothing left over to build up the intracellular granules anymore.
So your daughter’s condition is immutably different now than that of Razorback’s daughter at present. That’s the key. Probably moot, but I wanted to offer my help in case of one choice (between two) by Razorback.
There are precious few in the world who even KNOW that all cases of insulin-dependent T1DM are preventable if diagnosed, and intervened upon, early enough and adequately/appropriately. Including MDs. But there is no real question about this – there are plenty who are knowledgeable enough who DO know this. There is no challenge of which I am aware. Just not any effort to spread the word either, by medical and other institutions (including medical schools).
Did you know? I doubt that many on this forum do, or have. This requires a study of the long history of the relevant clinical literature, and an understanding of the biology of the T1DM condition (including reading of the basic research underpinning this). If you want a single reference with a lot of pure clinical experience, just read Dr. Bernstein’s writing on this one subject. It is 100% consistent with mine, and he DOES have experience with a number of parent/patient pairs under his care and successful staving off of insulin dependence.
I do not find many on this forum to be unusually knowledgeable about the biology of diabetes in general. Nor many anywhere. This takes a lot of effort and study and reading and time and motivation. Knowing about gadgets is what I do find a lot of on this forum – T1Ds use a lot more of them, and for them they are paid for by medical insurance. Purported knowledge about insulin mimetics and drugs is also common, but without an understanding of the biology both MDs and patients often draw incorrect conclusions and are not in a position to make the best tradeoffs necessarily, because they lack the “inputs” for those tradeoffs. They don’t recognize or understand all options to be traded off, in other words.
Anyway, we all have our own case history to rely upon, and in my case I have always compared this as a test against biological and medical hypotheses. And they so often, if not usually, come up inconsistent with just my own case, much more those which can be collected from the broad clinical literature.
I wish both you and Razorbacks the best of fortune and success with the T1DM. Practical experience has much merit, and in your case you have your own and your daughter’s case under your belt. I am not sure it is too practical for a parent with such a young child to overcome all of the hurdles necessary to maintain that child on an evolutionary diet, as is my own. But I am close to 63 years old now. Absent the evolutionary diet, there is no possibility of staving off full insulin dependence, as I hope I made abundantly clear.
For someone first presenting with polydipsia or polyuria or both (child/minor or adult), I CAN offer a wealth of practical counsel in how to do this. My most serious condition is a total lack of ability to generate antibodies to either polysaccharide antigens or to protein antigens. This is a well-recognized, but severe form of a, polygenic condition named CVID. It is the CVID that would kill me, within a few years for sure, if I were to deviate from the evolutionary diet. I can no longer eat ANY plant foods. The dietary restrictions of my HNF1-alpha diabetes are childsplay compared to those of the PID (primary immunodeficiency). I have a 3rd condition, tied to the HNF1-alpha mutations, that also is dangerous and prevents me from eating many or most plant foods, all by itself.
I have not personally solved the problem of transferring my own diet to that for a child – granted. But right down to the food shopping/storage and cooking, etc. I know as much or more than just about anyone in the world about how to emulate the evolutionary diet in the modern, urban world. Just as I have had to diagnose my own conditions, solely on my own, so have I had to work out all of my own survival and health-optimizing methods. There is much more than just the diet to that, as well. Much, much more.
We can put our cases predominantly in the hands of the MDs and the institutional framework around them (including drugs and equipment), or we can choose to do it my way. Most will go with the former – life is complex enough nowadays.
I guess my final, more limited post should be this:
In full “insulin dependent” state – the end game for almost all T1Ds – the alpha cells will undergo a predictable form of epigenetic transformation within a few years at most. The literature refers to the consequent effects with terms such as “loss of intraislet insulin decrement”. I would summarize the after effects as latent and sloppy glucagon response (to meal absorption). Hence, the mature T1D will be highly subject to hypoglycemia and hypoglycemic events that can range from unpleasant to dangerous and life-threatening in severity. This CANNOT happen without the genomic destabilization deriving from virtually 100% loss of intraislet insulin signaling. This also happens in advanced T2DM.
This is the irreversible (at least, so far in all of clinical history) consequence of complete loss of intraislet signaling. The fully insulin-dependent state is certainly manageable.
The tradeoff for someone still with ~ 20% of intraislet insulin signaling (more than adequate to be NOT insulin-dependent (yet)) is preservation of normally functioning alpha cells. With loss of most of the remaining 20% of beta-cell function the alpha cells will cease to perform normally – that is guaranteed.
If I use excessive bolus injection (of Insulin Reg in my case) my BG will drop down to that of the fully fasted state. The medical term for this is “iatrogenic hypoglycemia”. I will not be aware of this unless I make a capillary-blood glucose measurement. There is absolutely NO effect on brain or anything else. Not the slightest symptom. The normally functioning alpha cells, in combination with their direct and predominant regulation of liver, exquisitely manage fuel supply to the brain in their normal genomic state. Blood ketones will be raised to fully compensate for the lower BG of the whole-body blood supplied/managed via hepatic artery – immediately. I do have a blood ketone meter as well.
So preservation of beta cells is merely a goal to preserve alpha-cell function, as I see it. THIS is the big tradeoff.
P.S. As I recall, while I was under the “care” of Dr. Bernstein, he became annoyed that I added a few blood-BHB (ketones, or BK) readings to my written datalog of BG readings that he insists upon for each and every patient of his.
It took me a while to figure out why. But he expressed his irritation verbally to me, on our regular phone call – this is how he, uniquely, “sees” his patients after the initial visitation at his office (three full days for me).
After probably a few days at least, I realized that Bernstein had thought I was reporting BK because I was monitoring for ketoacidosis. Which he correctly insists does not require BK monitoring, since BG monitoring is more than sufficient. And that IS correct, insofar as that goes.
But no, that was not my purpose. It was because my BG had dropped in one of the readings to that of the fasted state – 20 to 25 mg/dL lower than in the fed state. And I was illustrating/confirming that the BKs went way up in compensation. BECAUSE my alpha cells are fully normal in function, unlike his own.
Bernstein does NOT understand any of this biology/endocrinology at all. He explains and models it completely incorrectly. Should have dawned on me as soon as he expressed his irritation, in his scolding manner which is a practiced and kneejerk response that applies to all of his patients – one size fits all.
So this is why I tend to try to teach the biology. MDs do not understand it, with precious few exceptions, including even maverick MDs like Bernstein who admittedly probably has the most clinical observational knowledge of maybe any diabetologist in the world at this point, because all of the others who preceded him in the earlier days when MDs actually observed things rather than going to a cookbook formulaic set of procedures – one size fits all – have died off since they were born before Bernstein.
And Bernstein learned, in medical school and elsewhere, from this same earlier generation of MDs who were actually compelled to use their brains back in the day.
Bernstein, during the first of three full days in his office during my “indoctrination” as an initial patient, lectured me and a young LADA MD (in mid-30s at the time) to-be, then in medical school (Bernstein had invited him to join us for the three full days that I alone had paid for, without asking for my consent beforehand, but I nevertheless had no problem with it) for a good long time about ketoacidosis and all sorts of fancy self-administered (prescription) drugs to apply, and how to apply them, in case of ketoacidosis emerging in our own cases, so that the response could be as quick as possible and not require going to hospital.
I had to pay for all of the expensive prescription med’s – they must be still sitting in a drawer in a bathroom cabinet somewhere in my house. I should throw them out, since they are of no use to me and I don’t know how I might usefully give them to someone else who might be insulin-dependent.
Bernstein does not still, and did not then, understand that for my form of diabetes there is NO possibility of my ever becoming insulin-dependent, and hence NO possibility of my ever becoming susceptible to ketoacidosis. NONE whatsoever. Because he does not understand the biology. He has not read the basic research of the last five decades and more.
So going to a pediatric endo, or any endo/diabetologist, will result in instructions based upon the cookbook(s). Even Bernstein, who knows that it is better in some ways, and quite feasible, to prevent the loss of 100% of beta cells in T1DM, and also knows that this condition is then permanent for life, nevertheless does not understand the biologically critical and fundamental role of the alpha cells and glucagon. FAR more critical to sustaining life than the beta cells and insulin. As the survival of so many diabetics well demo’s.
NONE of the five decades of basic research in the attempt to block glucagon and its pathways in animal models of diabetes have been successful in the long run. There are many, many ways to block or inhibit glucagon and its pathways, because hyperglucagonemia is the quintessential property causing hyperglycemia in all forms of diabetes (excepting MODY-2, which is not a condition of insulin deficiency at all). But none of them work, because the genetic expression of alpha cells compensates over time to the glucagon inhibition. And there are other means of compensation as well. Because glucagon is absolutely ESSENTIAL to life, from second to second. And insulin is only important for anabolism – driving AAs into the cells, primarily, with other secondary functions such as whole-body (basal) BG regulation, storage/mobilization of FAs into/from adipose, etc. Hence, insulin deficiency and consequent hyperglucagonemia can be very CRUDELY compensated for by subcutaneous insulin (administration) driving excess whole-body BG into tissues to bring down and normalize the hyperglycemia otherwise induced prandially (bolus insulin) and in between meal absorption (basal insulin) created by excess of delivery of glucose from the hepatic artery, in response to hyperglucagonemia.
The hyperglucagonemia will be everpresent for life in the diabetic, unless the condition is FULLY reversed and normalized in one of the acquired forms (T2DM or T1DM). And this is rarely achieved, though possible. In my own form of diabetes it is not even possible.
There is nothing physiological or endocrinologically equivalent, or even similar, between the action of administered/exogenous insulin and endogenous (islets) insulin. They are two entirely different mechanisms. The difference has nothing to do with speed of action of exogenous insulin. Inhaled insulin does NOT work to cover meals any differently, or any better, than subcutaneous insulin. Both are non-physiological and have the same limitations. Neither can correct the fundamental imbalance of insulin and glucagon secreted by islets, due to the paracrine endocrinology in endocrine pancreas. Islet insulin is the PRIMARY regulator of glucagon secretion by alpha cells. Hence, islet insulin deficiency WILL and DOES (always) cause hyperglucagonemia. This is the defining condition of all forms of diabetes (excepting MODY-2).
Fast-acting insulins of all forms do NOT reliably or predictably work to cover carb’s. They CANNOT – there is positive feedback and hence instability during the prandial/absorptive period of “covering” a meal. An optimal titration of injection will result in both hypoglycemia and hyperglycemia, at different times, during the prandial interval – i.e. oscillatory response. That is the way it works.
Dietary carb’s cannot be covered by insulins. When an artificial endocrine pancreas can be manufactured and installed onto the portal vein, in the location of the human pancreas, then there might be something more akin to normal “coverage” of meals.
And by the way, even in the youngest and healthiest non-diabetics there is a hyperglycemic response to dietary carb’s. There is NOT a hyperglycemic response to AAs. We are NOT adapted to eat carb’s in any significant quantity or with any significant regularity, as species of modern hominids over the last two and a half million years. We ate meat. The biology, as well as the archeology and the stable-isotope analysis of collagen derived from fossil remains, and lots of other massive and broad evidence, all is consistent with a super-carnivore status and inconsistent with any significant quantity of plants in diet. Until the dawn of civilization, only 10k years ago at most. A lot less for most familial ancestries/lineages. But even 10k years is at most 500 generations. Adaptation to a new type of food requires at least 1000 generations. The field of evolutionary biology has demo’d this eloquently and thoroughly, for all cellular organisms.
QED.
P.S. Once again, as noted in earlier post(s), I should have included in my just previous post that fully insulin-dependent diabetics are an exception for “covering” meal carb’s. Because there is NO insulin secretion in islets, and hence the positive feedback in response to portal glucose is eliminated.
So that is one “advantage” of full insulin dependence. Not a good one to achieve, in my opinion, at the cost of losing normal alpha-cell function and at many other costs. But it is true that complete loss of all beta-cell function results in a predictability and consistency of bolus insulin to compensate for dietary carbohydrate of starch or glucose (in simple sugars) form(s), all of which becomes glucose (monomer molecular form) in portal vein after passing through gut.
Because Bernstein uses his own case as the reference for how he treats all his patients, he thinks that there is merely a latency (of effect of subcutaneous insulin) and potency problem with eating carb’s. He does recognize the problem of unreliability/unpredictabilty. But he does not understand the FUNDAMENTAL difference in the response of diabetics NOT fully insulin dependent from those that are, like himself.
Hence, his formulas for titrating insulin do NOT work at all for a non-insulin-dependent diabetic. I can attest to that, and have always understood it. Bolus doses are a matter of flux rates in blood and organs for insulin and the meal/portal nutrients (AAs and glucose), for one thing. Static analysis, using a factor or ratio of dose to grams of AAs/glucose in meals, does NOT work even for an insulin-dependent diabetic but even less so for any other diabetic. It does not at all reflect the endocrinology nor the cellular biology.
One of the reasons that HbA1c can never be brought as low in either (most cases of) T2DM and in MODY (excepting MODY-2 where insulin is not, and never should be, used at all) by subcutaneous insulin and in mature T1DM and advanced T2DM is the fundamental difference of an extant intraislet insulin signal in the former, and absence of such in the latter. This is the universal experience in patients of Bernstein of both categories, and of non-patients who nevertheless practice a disciplined form of insulin therapy to come as close as possible to normalization of BG.
Those with a remaining intraislet insulin signal cannot get down in the range of the mid 4’s, and will typically be closer to mid 5’s (% of glycated HbA1c in blood). I myself can achieve 5.0, but am on average 5.2. That is about as good as is possible for someone with an intraislet insulin signal remaining. Whereas for the fully insulin-dependent HbA1c can be fully normalized to 4.5%, give or take a bit.
Bernstein advocates a target of ~4.5% for ALL forms of diabetes. It is NOT possible in most cases of T2DM nor monogenic insulin-deficient diabetes. He does NOT understand or recognize this, nor why. Due to a fundamental, enormous hole in his understanding of the biology.
We did more testing today. Her c peptide has went down to .92 (.90 in cut off for this test) her insulin level was 8.9 (0-17.0 normal) we are waiting for 2 hour GGT results.
So far her 1 hour came back as 97 with c peptide 3.86. Her levels have been steady fasting 110-130 the last 2 weeks. I mean can type 1 have a honey moon before starting treatment, I give up I’m exhausted and I do not understand what’s going on anymore 
.
Honeymoon period is common: often going for several weeks or longer, even months.
Need to check glucose often and if this is early T1DM, I’d suggest to start an appropriate long-acting insulin to preserve islet function, avoid high-sugar drinks and avoid high- carb diet in general.
I’m not sure if I’d recommend an extreme protein-centred such as is occasionally put forward but everyone has their own vie on that topic as you’ve seen.
I’d want to see evidence of autoimmune islet cell destruction before jumping to diagnosis of T1DM.
Her 2 hour came back higher than her 1 hour how does that work 
it was 112.