Does everyone eventually get hypo unawareness?

Unless we quote sources all the myths about diabetes continue. These are the myths that allow people to declare that T1D’s can’t be allowed to do stuff that other people can; like, famously, the British Sub-Aqua Club [BSC: http://www.ukdiving.co.uk/information/medicine/diabetes.htm].

There’s more than enough evidence on this thread that disputes the original claim. This is not wikipedia. A lot of this is original research and it needs to be because if you go with the wikipedia approach you just end up with a distillation of the current myths and legends.

Personal experiences quoted on this page are hard scientific evidence. Repeated quotes by one or other bunch of do-gooders are apocryphal at best. See the evidence of elver above; if you take both that (DMV) approach and this apocryphal statement from the Dutch ([https://www.diabetestype1.nl/bibliotheek/dagelijks-leven/319-nieuwste-inzichten-over-hypo-s-en-hypo-unawareness):

Na ongeveer 5 jaar diabetes type 1 werkt de reactie met glucagon niet meer.

[TR, Google:] After approximately 5 years of type 1 diabetes, the reaction with glucagon no longer works.

Then apparently all T1D’s should be banned from driving after 5 years. Notice that the quoted Dutch assertion is an absolute statement (“the reaction with glucagon no longer works”), assuming Google Translate got it right (my Dutch is extremely limited but the translation seems correct; “niet meer”.)

I can assure you that I have been a T1D for more than “ongeveer 5 jaar”, like 47 years, and I have a physical glucagon response that works. Mine hardly ever kicks in because I have a mental low blood sugar response that also works and I know what it means. My non-diabetic wife is only now developing the mental “I need something to eat” response; her BG will drop to around 60 mg/dl, she notices then, I notice at 70-80. Specifically at 8:55AM while writing this my hypo-awareness just triggered; my G6 reads 88mg/dl descending, my Contour Next reads 77mg/dl and my hypo-aware self says “eat something”. I looked at the G6 and meter because my mind hypo trigger happened, not the other way round.

So where is the original research that the OP asked for? It isn’t some article on www.diabetestype1.nl, a Dutch analog of tudiabetes. These are all regurgitations of sets of medical opinions derived, maybe, from some original research. All we have at this point is the review paper identified by Boerenkool, the OP:

This review will focus on the more recent developments in our understanding of the mechanisms that underlie the sensing of hypoglycaemia in both non‐diabetic and diabetic individuals, and how this mechanism becomes impaired over time.

This is a review paper; a scientist summarizes a set of other original research papers so that other scientists don’t have to read (or, indeed, understand) them. It’s 11 years out of date. It has received 39 citations, that would be low for original research but it might be how it goes for review papers (readers will often cite the original research not the review).

Part of the problem is the “pay for access” thing and the fact that there is so much bad scientific research that if you don’t have full time (institutional) access and spend it following the research it is difficult to distill the bad science from the good. This is why review papers are useful.

There are two things happening here and it is VERY important to separate them:

  1. Hypo-awareness. Humans as a group are not hypo-aware because the symptoms of hypoglycaemia (or hyperglycaemia for that matter) are not unique to hypoglycaemia. Hypo-awareness has to be developed and that takes time; evidence, personal (my own and my non-diabetic but blood testing wife.)

  2. The glucagon response. For T1Ds this seems to change over time to adapt to wider fluctuations in blood glucose, but it’s not clear to me how much it changes. I haven’t seen any evidence to support the Dutch statement above; that it absolutely fails. If it did I would be absolutely dead; so I can simply refute the assertion by typing this (oops, am I a ghost?) This is because when I was first in Oregon I proceeded into the woods with a chainsaw to work off some serious emotional stress and forgot to take my glucose tablets. After cutting a few sticks I became so incapacitated that my voluntary control of my muscles ceased, failed. I had enough control to cut the saw but nothing else. After a while on the ground I was able to get up and return to the house with the normal symptoms of a glucagon response. Just to make it clear; I am not dead.

This is, of course, consistent with Boerenkool’s second quote above, but note that there are still two things here; hypo awareness and when the glucagon response kicks in, what BG level. It makes complete sense to me that T1Ds should develop an increased ability to be aware of hypos at the same time our bodies adapt our physical glucagon response to deal with greater fluctuations in blood glucose. This is good because we don’t want that horrible glucagon response kicking in if we can avoid it; we have the technology. We have the capability to eat glucose tablets; better than glucagon, faster, controllable.

The abstract of that 2008 review paper is also consistent with the changed response. Of course there is always a spin: emphasis added below:

During hypoglycaemia, glucose‐inhibited (GI) neurons may be regulated by the activity of AMP‐activated protein kinase. This sensing mechanism is disturbed by recurrent hypoglycaemia, such that counter‐regulatory defence responses are triggered at a lower glucose level.

So let me rewrite that in a non-judgmental form:

Scientists hypothesise that an AMP‐activated protein kinase regulation of glucose‐inhibited (GI) neurons adapts to the greater fluctuations in blood glucose observed in Type 1 diabetics so that counter‐regulatory defence responses are triggered at a lower glucose level.

If correct this would allow Type 1 Diabetics more time to respond externally to low glucose than observed in less capable non-diabetics. The changes in the levels at which the relevant hormonal response, glucagon production, is invoked along with increased awareness of the symptoms of hypo and hyper-glycaemia mean that Type 1 diabetics are significantly more able to deal with the blood glucose regulation issues after 5 or so years.


Non-judgmental postings are great.


FUD brings topics FOR DISCUSSION, to the entire group. We don’t learn if we don’t ask questions. The OP made no “original claim”. The OP stated claims made in an article, then ended their post with question marks. Question marks are used to ask questions and engage in learning.


This response was great, filled with good analysis of the article and definitely far above your OP on this topic since it addresses the “question” of the OP in a non-accusatory and polite manner where everyone reading can learn something potentially. We are all about learning and growing. We take articles and analyze them…that’s what scientific minds like to do and I think most people enjoy discussions around ANY D-related topic, no matter how far-fetched it may seem.


Exactly, I read the claim and didn’t want to take it at face value. So I came here to ask whether it is grounded in actual research.


Which is exactly what we do here. We find an interesting article, no matter how far-fetched it may seem and we bounce it off the wall here in FUD. Your original intent was observed and recognized by most. :slight_smile:


Based on this post, I kind of fail to see where we disagree. I asked the question because the magazine did not cite any original research and I don’t want to believe or propagate myths. The claim on diabetestype1.nl seems to come from a summary of a talk at a conference in Lisbon in 2017. Still no original research. But at least it helped me find the review article. That’s more than at the time of my question when my google scholar searches returned no helpful results. Via the review article the 5-year claim can be traced back to a 1994 article, which I can’t access right now. Of course, that doesn’t mean the question whether the glucagon response is impaired after 5 years of diabetes is settled. A 25-year old paper probably sparks a lot of questions about the methodology, influence of the treatment back then and host of other things.


Based on this post, I kind of fail to see where we disagree.

We don’t disagree at all. True, I “replied” to your original posting but the reply was definitely directed at the posts which regurgitated the same myth. I replied to you to avoid specifically citing posts that I thought were problematic.

We do, I think, undervalue the original research that happens here; when 5 or 10 or 20 people quote a personal experience the result is 5 or 10 or 20 times better than 1,000,000 quotes of a 1994 article :wink: Personal experience does refute the assertions made about lack of hypo awareness.

The whole methodology of determining what the review article called “counter‐regulatory defence responses” seems mysterious to me. A person with functioning beta cells produces the normal “regulatory” glucagon response which prevents the “counter-regulatory” response because it causes the alpha cells to immediately release glucagon.

The hypothesis seems to be that the “counter” mechanism “normally” kicks in well about 54mg/dl (3mM) because that is identified in one of the other references as a “failed” glucagon response. But the non-counter mechanism certainly operates before this (it maintains BG at almost exactly 80mg/dl). How, then, was the non-failed BG (counter-regulatory mechanism kicking in above 54mg/dl) obtained? Clearly not from anyone with beta cells, because they result in the non-counter regulation. So a group of people who had T1D for less than 5 years and who had absolutely no functioning beta cells whatsover were tested in 1994?

My working hypothesis is that the “5 year” period is just the “honeymoon” period and these researchers are looking at a regulatory glucagon response that just disappears when the last beta cell dies.

Yep! I don’t have diabetes. But I wore a Dexcom and noticed I ran low much of the day and only noticed when my blood sugar ticked from 60 to 59. Then I became shaky and weak. Before that, I just felt a little bit tired but would never have identified it as a symptom of hypoglycemia.


just out of curiosity, what is considered a hypo for you? i am perfectly comfortable at 55, but then if i am in the process of dropping into my 40s or 30s, i am a shaking sweaty mess. i’ve been Ti for 30+ yrs. (when i was first dx, if i went into my 70s, i was a terrible mess, but i think that has to do with the fact that my body was used to being in the 300s for so long.) also, there is a big difference between crashing quickly and just sliding down low. when i am crashing, i can feel it more significantly than if i am just trending low.


A hypo is anything lower than what I would expect to see regularly in someone without D. I consider values in the 60s to be mild hypos (as long as I’m not falling quickly). My symptoms are equally mild at that point (a little anxiety or hunger… if I’m working out then my muscles will feel a little weaker too).

Symptoms in the high 50s are similar. Low 50s can bring a much more urgent hunger and less energy (slow walking and weak muscles). If I dip into the 40s I could experience spots in my vision, numbness in my tongue, and a ravenous hunger. I also might experience a jerking sort of motion where I have difficulty holding something in my hand. If I dip below that my memory isn’t very good.

If I’m falling fast the bad symptoms come at higher values.

I haven’t experienced shaking in a long time, but I think I have sweat during a bad low at some point. It’s not a usual symptom though.

I don’t have bad lows often, but those are the symptoms I have had when they have occurred.

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I’m not sure if 60s are truly hypos, since I as a nondiabetic spend a significant portion of my day in those numbers, at least according to Dexcom. But, for my kid I consider it a hypo because I think he does feel low at that level. I think probably because he’s a kid – I suspect they just run naturally in a tighter range (less highs, less lows).

I’m basing it off of a study we’ve referenced a few times on here.

“The mean 24-hour capillary blood glucose concentration was 90.9 ± 6.8 mg/dl (16 values per 24 hours), and mean blood glucose concentrations at daytime and during the night were 92.7 ± 6.9 mg/dl (14 values per day) and 78.1 ± 7.9 mg/dl (2 values per night)…

Premeal capillary BG concentrations were 80.9 ± 7.8, 80.8 ± 6.8, and 84.8 ± 8.4 mg/dl before breakfast, lunch, and dinner, respectively.”

The study does state that the minimum interstitial glucose value observed was 59 mg/dl. I feel like the reliability of cgms and insterstitial values varies a lot from person to person though. I don’t know anything about the equipment they were using.

In any case, I personally don’t think there’s anything harmful about values in the 60s. I don’t correct above 65 mg/dL if I’m sleeping. My alarm is set for 65. Since 59 is the absolute minimum in this study, I have no interest in staying in the low 60s for long- especially considering that that is merely my cgm value. Dexcom is pretty reliable for me, but I consider reliable to be within 10 mg/dL of my actual blood glucose value.

I’m not comfortable basing my hypoglycemia range or hyperglycemia range off how I feel because my body tends to adapt to whatever range I stay in the most- as @daisymae mentioned in her post. If I were to hover in the 200s most the day then I wouldn’t feel bad in that range like I do now. My hypo range adapts in a similar manner. If I spend multiple days running low or in the 60s, then my symptoms in the 50s and 60s are less pronounced.

I don’t think we know all the repercussions of hypoglycemia and at which level harm truly occurs. I know Eric has posted a paragraph out of a textbook about it, but I guess I need to see a study where they’ve measured all the things that could be affected.

I do not remember what occurs during severe hypos (30-40) very well which always worries me. I want to limit my exposure to anything that impacts my brain like that. If I have no reason to believe most people without D are in a range regularly, then it’s probably best avoided IMO. I used to be less worried about it, but I think there’s a lot about the brain that doctors and scientists don’t understand yet, and doctors are much more leery of hypos than I am.