“For most T1’s, the liver does not respond to low blood sugar. Generally after 5 years, the alpha cell’s glucagon response is gone, and the epinephrine response to hypoglycemia is also impaired.”
I find that comment interesting. I have read that Type 1 diabetic’s alpha cells (spared and located in the pancreas) actually produce more glucagon over time although this availability isn’t always reliably communicated to the liver. Sometimes there is more and sometimes less response than needed. My personal research (n=1) is that after 21 years of being a type 1 diabetic my liver can dump glucose (to excess) whether I need it or not. I have to up my basal to 150% at 5:00am to stay normoglycemic. Thanks, liver.
I think Eric was referring to the livers ability to dump sugar in response to a low. The well documented dumping of glucose in the morning (aka dawn phenomenon) is a different physiologic response than dumping glucagon in the presence of a low blood sugar. With that being said, I have read that diabetics have differing levels of alpha cell activity, although in all Type 1’s it is changed. I suspect that if you mapped alpha cell activity you would find that people with little to no alpha cell activity would have formerly been labelled “brittle” and those with more preserved alpha cell activity “good diabetics”
Also for completeness - this statement is not including the alpha cell’s response to prolonged periods without insulin in t1d (and thus the liver’s response to glucagon, epi/norepi, and cortisol during DKA)?
(edit): even in formerly labeled “brittle” diabetics
Chris: Hmmm, I thought it was all a grand cascade of events. The alpha cells produce the hormone glucagon, which travels via the portal vein to the liver, where it triggers stored glycogen to be converted into glucose, which the liver releases into the bloodstream, increasing blood glucose levels. This same mechanism is the body’s response to hypoglycemia no matter the cause.
Yes @Chris and @LarissaW, I was not thorough in my response.
Yes, my liver still stores glycogen, my liver still responds to cortisol and adrenaline (I see those spikes all the time!), and my liver still responds to 4am with a glucose release , and my liver still responds to glucagon.
But my alpha cells don’t release glucagon for lows, I have to inject glucagon or have someone else inject it.
So to be more exact, I should have said the “the alpha cells do not respond to low blood sugar”, rather than “the liver does not respond to low blood sugar”.
That is what I was trying to say. That would have been a better way to say it.
Here is a decent paper from 2014 talking about the complications of both Alpha and Beta cell dysfunction in Type 1 patients, it also alludes to, but doesn’t fully address all of the complications of the system.
Thanks for the link. At some point I’ll check it out. I haven’t studied up on pancreatic alpha/beta cells much since I did so when starting Symlin, years ago.
Sure, be happy to. I was excited to start Symlin (amylin) as I was hoping it would allow me to maintain my good numbers but using less insulin. The primary objective was to lose some weight. And that is exactly what happened. Initially, over about a week, I ramped up to the full dose, didn’t experience any nausea, was able to avoid hypoglycemia by carefully watching my numbers and my TDD of insulin dropped by 30%. Over the next six months I lost 17 pounds (of the 25 I wanted gone).
Then, just as Gary Scheiner reports in the link below, it stopped being as effective. I started to need more insulin for the same food intake and exercise. And this is a fairly expensive, high-maintenance drug, requiring injections with all meals consisting of at least 25-30 grams of carbohydrate. The good news is when I stopped using it I was able to maintain that weight loss. So, I consider my experiment a win, I’m glad to have used it, I only wish it would have worked for years instead of months. Here is a nice link. I found it to be accurate and helpful:
I have a T1 acquaintance who picked up use of it in order to help with his appetite. I can’t be positive, but I think he has reported being quite a bit overweight. I wouldn’t say I’m interested in it for the purposes of weight loss (though there are times I wouldn’t put up a fight at the suggestion), but I am interested in the concept of it helping with appetite suppressing hormones… because mine maybe have all washed up. I don’t even know if there’s anything to the theory (or even what the theory is) that some type 1s lack the hormones that help with hunger, but if it’s real, I think I’m one.
Sorry this is long-winded, but does the weight loss you mention have anything to do with this idea, or am I connecting things that don’t actually belong together (my personal favorite pastime)?
I assume you meant to say “I have always seen it given IV continuous drip.” I can say that when I have been treated for DKA, I have been given insulin via IV push, although not nearly enough, but I will come back to that a little later. I certainly know that if you are talking about treatment administered by an ER or floor physician, I am in no way willing to take “best treatment” practices from either. Heck, think back to all the endos you have seen, and read posts on here - I am not even willing to take best treatment practices from any endo.
There was a post a few months back from a mother, who was a physician, indicating that she, and the child’s regular endo, had to fight with the floor physician about treatment protocol when a child was admitted to the floor for DKA. And while I only have my own experience to go off of, I can say that when I have been inpatient, I have never had the endo come in on rounds and say “carry on, everything looks good!” Instead, it has always been, “change the orders to this, and this, and this.”
I can find no actual studies supporting that. Instead, what I see are studies showing that the half-life ranges to be 15-30 minutes, and following those results, statements along the lines of ‘despite the COMMONLY BELIEVED half-life of 4/5 mins.’ One such study is referenced at the bottom. I can say personally, that there is no way IV insulin injections stop having significant action for me at 5 mins. Anyone else have a 5 min experience?
I won’t say that hospital physicians are cowards, but I will certainly say that 1) they don’t have the time to monitor the effects of IV insulin push/injection, and MORE IMPORTANTLY 2) they have no idea what a correct dose would be, because they don’t take the time to establish any reasonable basis for what insulin doses to give. The last IV push I was given was less than the smallest bolus I give for a normal meal. There was no way that was anywhere near enough to have a significant effect on reducing the extreme level of my BS at the time. If you are lucky an ER or floor physician may ask what your total daily insulin use is and make some rudimentary calculation based on that. However, I think we recognize that those are useless measurements right? Total daily insulin use is significantly affected by what I eat regularly, especially how many carbs, and how much regular exercise I do. If they really wanted to effectively derive a somewhat accurate dose, wouldn’t they be asking me questions, or looking in my chart, for values like correction factor/ISF/sliding scale???
I firmly believe that unless they are an endo, or have significant experience with diabetes, they have absolutely no clue what numbers should be. I mean before the advent of electronic med recs, you could tell them your last BS was 10, 100, or 1000, and pretty much anyone but the endos office would write it down without batting an eye unless they had “normal” range printed on a lab report sitting right in front of them.
Most importantly, I think the advice of CAREFULLY applies to any new treatment until you learn exactly how it works for you. Decades ago when I started on MDI’s, they didn’t just give me 1/3 if the bottle the first time. I started conservatively, and on what was thought to be the low dose side, and then gradually fine tuned the dose to one that worked for me.
I wanted to feel less hungry and Symlin delays gastric emptying. And that is exactly what I noticed for those first few months. I didn’t feel stuffed or uncomfortable, I just didn’t think about food or snacking as often. And when I did eat as long as I gave the Symlin 15 minutes before eating and then didn’t gobble my meal, I ate less of what was on my plate. How much of all that was emotional and could have been precipitated with a placebo? Don’t know. If you give it a try I’d very much like to hear about your experience.
I have never seen an order for IV bolus insulin in the clinical setting. Nor have I given it in that manner. Rather, only via continuous IV drip, through an electronic IV pump, with the dose titrated for effect.
You are right when you say, “…there is no way IV insulin injections stop having significant action for me at 5 mins.” The half-life of a drug reports how quickly it is metabolized and filtered out of the bloodstream by the liver and kidneys. It does not report how long the effect of the drug can be observed. Two very different things. When you are looking for data on the half-life of insulin make sure the study is talking about regular insulin, given IV bolus, to healthy (no liver or kidney impairment) human subjects. By the way, the study you linked to was done on patients in DKA with doses repeated at two-hour intervals. Again, not a good methodology if the objective is to determine the half-life of a drug.
As to the rest of your response. I’m sorry you’ve grown to hold the medical community is low regard but I can’t enthusiastically disagree with your opinion. Unfortunately, we, all patients, must be informed and our own best advocates when navigating any illness. The tragedy is that doing so is often not possible for many patients, for lots of good reasons. I’ve taken the tac that I’ll do the best I can for myself and others and then move along. More than beating cancer, diabetes, arthritis, heart disease or any other life challenge, my goal is to not go out of this life a bubbling mass of anger. And with that bit of corny existential philosophizing, I’m outta here.
A good approach. Difficult to achieve, but a great goal nonetheless. I hope you don’t feel that the entire vibe here is one where the medical community is held in low regard. With that being said, more negative stories are going to bubble to the surface than positive ones. Just the nature of the beast.
Drug half-life is the time it take for the concentration to be reduced by 50% . To talk about drug half life in terms of being metabolized and filtered is an oversimplified version of the definition. I understand that often it is explained and taught this way because a vast majority of pharmacokinetics and pharmacodynamics involve substances that are “foreign” material to the body and consequently undergo breakdown by the digestive system and “filtering” by waste removal systems. However, when we talk about rbiologics, especially digestive ones, half life isn’t significantly affected by filtering it out because it isn’t a “foreign” or “waste” substance. Certainly feed back loops affect rbiologics, but when we talk about insulin during high BS, we are in the loop chain that is calling for release/non holding of insulin so that BS can be reduced.
Considering that insulin in a transport protein, we even lose the ability to estimate part of half-life in terms of cleaving/uncleaving from conformational changes or desired bonding priorities. It is simply a “one and done” protein. So to say significant action of insulin is still being observed at 5 mins, really says we have not hit the downhill slide of more than 50% of the dose being gone,
I don’t believe there would be a study of insulin half-life on people who weren’t diabetic and experiencing high BS. 1) Without a “marker” for the IV insulin specifically, there would be no way to differentiate it from en vivo insulin in a non diabetic, and for a diabetic, obviously if there was no “other” insulin draining into the bloodstream, the BS would be high. A “marker” naturally questions study results because you have to be able to rule out the artifact as a contributory factor to changes or filtering. 2) It is fundamentally obvious that diabetics in DKA are the target recipients of IV insulin treatment. Studying IV insulin treatment in another population would be akin to studying Midol in men. WHY???
“I hope you don’t feel that the entire vibe here is one where the medical community is held in low regard.”
Oh, no, of course not. Poor medical practice, although not the norm in all areas, is common enough to rightfully provoke outrage and push-back. And when discussions go argumentative I tend to sit back and let it be. So, no worries, this isn’t my first rodeo.
Glad you feel that way. Having worked within many hospitals it is always amazing how different the facility standards can be even within one city. There was one day though that stands out in my memory when a group of nurses took a little bit of revenge on a patient which defied the otherwise high standards that the facility had. The patient was a police officer that had given almost every nurse in that unit a ticket because he hung out on a main feeder road leading to the hospital and the unit I was working with had many emergencies so the nurses were often in a hurry getting to the hospital. The poor bastard needed a tilt table test and never knew what hit him. Before they administered the drug that was required, they put the poor guy through the ringer and ensured no more tickets would be forthcoming. The good news is that the tilt was negative, so no diagnosis and no tickets.
Oh, my. That is both funny and not. I was fortunate to have spent my entire nursing career in large, teaching hospitals. All forty years were ER or ICU. I’m a stress junkie. I’ve seen extraordinary care and pretty poor care, but that later was fairly rare. Bad apples tended to move along. Pity, that means they become someone else’s problem. Thanks for moderating such a great resource.
, and my liver still responds to glucagon.