Is Strict Control Sensitbe When Faced with Hypoglycemic Memory?

According to the theory of hyperglycemic memory, if the patient has ever had hyperglycemia its effect is stored in its epigenetic effects, so even if the blood sugar is later normalized, the ‘stored’ hypoglycemic memory can continue to cause damage. This sounds like a bad hypothesis, since essentially it says that complications arise in the presence of high blood sugar, and oh, by the way, they also occur in the absence of high blood sugar, because of a hypothetical entity we have constructed to save the theory called ‘hyperglycemic memory,’ which carries forward the effects of hyperglycemia long in the past.

Since I have now survived with type 1 diabetes for 51 years, like all current long-term survivors I spent about the first twenty years of the disease with extremely poor blood sugar control, since there was no way to measure it, since the home glucometer hadn’t yet been invented. So my hyperglycemic memory has to be considerable, and a powerful force for causing new complications despite strict blood sugar control.

So what do I do now? Over the last decade, my A1c has been consistently in the 4 range, so my control has been excellent. But the rate at which my complications have been developing or worsening has been faster than ever before in my life. For example, in the first 40 years of my disease I required two laser photocoagulation treatments for retinopathy, but in the last 10 years I have required 4 treatments, because it has been getting worse faster. Since there is nothing else which can be causing this than metabolic memory, unless it is the combination of greater age with even well-controlled diabetes, what use is the strict control I am maintaining now? It doesn’t seem to have any effect whatsoever in stopping complications, and it is both a lot of trouble to maintain and also extremely dangerous in terms of severe hypoglycemic episodes.


Strict control aint gonna hurt you, but if you don’t feel like you are in good control, that’s a whole other matter, right? You are having severe hypos? Lets discuss that. Discussion often helps me problem solve. Maybe you’ll clarify something about what your wrestling with.

As for the retinopathy, that’s a real bummer, Seydlitz. My friend is going blind. I am really uncertain how to accommodate him. His wife is brilliant, though. She will have fabulous info if I have the guts to bring it up. I don’t. Let me know if you stumble across anything helpful.

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I must admit I have never once read about Hyperglycaemic memory before, but having a quick look online it does appear there are a number of legitimate scientific papers on this, although it appears to be in it’s early stages.

Even if this was impacting you, my thoughts would be that you will still find keeping your diabetes under strict, or tight, control now will limit any further problems you have. I can certainly imagine it’s difficult to keep it up, when you feel like it’s not making any difference. The question, and this can only ever be hypothetical, is where would you be if you hadn’t improved your control?

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But think of all the new complications we are saving with good BS control now.


I have never heard of this, either, and if it’s true, it’s somewhat depressing for those of us diagnosed as kids in particular… But I tend to agree with @Donman90 that tight control can only help, and that things may have been even worse for you if you hadn’t been maintaining such tight control for an extended period of time.

@mohe0001, I just wanted to let you know that I’ve been legally blind since I was born, use both visual and non-visual techniques in my everyday life, and have a lot of experience working with people of all ages with visual impairments. If you have any questions in particular about resources for people who are losing vision or just questions about how to accommodate someone who is vision impaired or blind, I am happy to help in any way I can.


The DCCT was a much shorter study than your or my time with T1. But they found no A1C threshold below which there were no complications. In large part there were no DCCT participants with A1C’s in the 4’s so there isn’t really anything to compare it to. I’m not sure there’s any study that shows the risks going to zero at some A1C or bg level.

I don’t think we have to feel bad about poor control 30 or 40 or 50 years ago. To quote Jon Favreau, “you’re living in the past, man! You’re hung up on some clown from the SIXTIES man!”. OK that was about Bozo the clown and not the stone knives and bearskin days. It’s great that we got out of the stone knives and bearskin days.

We can aim as low as we want but no study out there guarantees that we won’t get complications, all we know is it’s a factor that helps reduce our risk.

There some other tricks we can use against the microvascular complications (retinopathy, kidney disease).

For example keeping blood pressure low (a progressive target even lower target than the general population) reduces an orthogonal risk factor, and ACE inhibitors are known to have further risk reduction.

If I get 50 years in (15 more years to go) and my only problem is progressing retinopathy, that will be such a huge success story.


Although in theory I should be avoiding complications by keeping the A1c in the 4 range now, there is no way to tell, since the effects of hyperglycemic memory simply swamp any benefits I might be getting from the present blood sugar results. Another important thing to consider is that I have reached an age when my additional life span is low, so even if strict control is permitting me to avoid generating new complications now, I won’t survive to experience the effect. Since I have an intrinsic variability in insulin requirements which is quite extreme, and the amount of insulin needed to keep me in a normal A1c range can rise or fall by a good 30% in a day, even with keeping the amount, timing, and nature of the food eaten constant from one day to the next, and the activity levels constant from day to day, there is no way to avoid severe lows if I am trying to maintain strict control.

Seydlitz, I’m only 50, and I’ve had docs tell me that I’m old enough that I don’t need to aim for super-tight control anymore :-).

My docs do have some valid points about maybe putting more effort towards cardiovascular health (in addition to the diabetes risk factors, that are not necessarily reduced with low A1C’s, I have a long and deep history of heart disease in males in my family history).

I don’t view it as a zero sum game the same way my docs often talk about it (as in they say I should move my efforts from bg control to cardio health).

I think keeping my bg control tight helps reduce risk of cardiovascular issues (not a magic bullet but helps) and it’s certainly true that, say, doing exercise without also putting effort into bg control is a sure way to cause more hypos.

So I cannot disentangle the two in my head.

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Yes, @Jen. That’s super helpful. Its tricky because he can kinda see, and kinda not see right now. Its an awkward period of transition. He’s a big computer guy and art guy. It might be nice if he started transitioning into computer resources before his vision goes out completely. I think he is still trying to adjust to the idea of loosing his vision.

@Seydlitz, that’s an issue. You have a Dexcom? One trick that someone mentioned was to put their Dex in an empty glass overnight, so they actually hear the buzzer and wake up when it hits the BG = 70 alarm. What are your theories about where the variability comes from? Any ideas or do you consider it just random ‘noise?’ Do you still recognize hypo symptoms?

This describes me my whole life. :slight_smile: About 90% of “legally blind” people still have some residual vision.

In the past, people used to wait until they absolutely needed assistive technology to begin using it because they needed to apply for funding (and be approved) or else shell out $1,000+ on software and even more if they needed hardware ($5,000 for a video magnifier, for example). But these days there are a ton of free tools available. On Windows there’s a built-in screen magnifier and a built-in screen reader. There’s also NVDA, which is a free, open-source screen reader that is very functional. On the Mac side, there’s a built-in screen magnifier called Zoom and a built-in screen reader called VoiceOver. On the iOS side you also have Zoom and VoiceOver. On the Android side, there’s a built-in screen magnifier and also a free screen reader called TalkBack that is either included or can be downloaded from the Play Store.

All of these take some training, of course (especially the screen readers, since they use the keyboard and/or touch gestures for navigation), but let me know if your friend is ever interested in using them and I can provide some basic “getting started” instructions.

ooooh, that’s good stuff, Jen. Thank you. I will send him the links.

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Unfortunately, if I go low while sleeping, that just drives me into an ever more profound sleep, from which a marching band rehearsing in my bedroom would not awaken me. Usually, when someone has treated me in the morning, they will say, “Hey, did you know you woke up at 38 this morning? I gave you a glass of non-diet Coke to drink.” I will have no memory of what they are talking about, and they could be making it up for all I know. I am still sensitive to lows when I am awake, since I can experience them as a unique sort of tiredness, but all the classic neurological signs, such as trembling hands, buzzing lips, etc., are missing.

I had never heard of hyperglycemic memory. I can’t find much on it. Is this something that has been proven or is it a theory? I think you are at much greater risk for the serious complications with higher Bg than with the possibility of HM.

oh geeze, your one of them. That’s tricky. I understand better. Have you been like that your whole life?

I pump adrenaline when I’m I’m low so it wakes me out of a dead sleep. I sit straight up in bed, ready to throw a chair and fight a gorilla.

This is one of those huge dividing lines between diabetics that puts us into two camps and makes it important to know who were talking to. I understand where you are coming from. What’s your tentative solution? You comfortable running around 200 or 250? Does that fix it, or do you have to run higher? When do you start feeling symptoms of high BG?

I’m all right maintaining the A1c in the 4 range, particularly since that allows me to fall to a level which most people would find too low, but which still allows me to be functional. When the spontaneous blood sugar fluctuations die down, I can keep everything well controlled with no severe hypoglycemic crises, and the same is true when it spontaneously shoots upward, since then the insulin dose can’t keep up with it. But the problem comes when it starts spontaneously plunging downward, since I can never guess how fast the dose has to be lowered to match it. For example, I began the summer having to take 15 units of Humalog per meal, but now, with the same array of things to eat, in exactly the same amounts, at exactly the same times, and with exactly the same activity level before and after, I now need just 2 units.

I also have never heard of hyperglycemic memory. And I must say, I worry enough about things I can control. If this is something that might have merit, I can do anything about it, so I am not going to worry about it.
But, I like many of us long timers, did not have the best blood sugar management back with one shot and urine testing. Or with visual blood testing strips and two shots a day. When A1C’s first started I was in the double digits most of the time. It was brutal. But over the years, I have learned a lot and worked as hard as I think I need to, to try and make things work.
The reality is the disease doesn’t play fair. You could run the best numbers out there, eat right, exercise all the time and still have major complications. Or you could have a history like mine and be running double digit numbers and have no complications. It’s not fair. It never has been and it never will be. I thank my lucky stars that my genetic makeup, while it gave me diabetes, it has also given my the genes that have protected all those systems that diabetes loves to destroy.
So while I do the best I can with a treatment plan that works for me, I continue to worry about those complications that may happen. But I don’t let any of them control my life. I have learned to do the best I can and when I make a mistake or things don’t work like they should, I try and learn from it and move on. So here is to moving on. I hope and pray, you can get a handle on the complications and get the care both physically and mentally for them. Good luck and keep us posted.


You aren’t stacking your insulin are you? I had issues with that. Now, I wait 4.5 hours for correction to work its way out of my system, and 2.5 for meal bolus. If I only have one of those influencing the system at a time, I can generally keep track.

No, I just match the insulin to the meal size (always the same) and the existing blood sugar level when I start to eat (varies incredibly, despite doing the same thing all the time and eating the same amounts of the same food at the same time every day for the last ten years). What causes the chaos is the spontaneous rising or falling of the insulin requirements, which means the same size and content of meal can require up to 7 or 8 times as much insulin in June as it does in September. I used to think it was varying degrees of stress, allergies, or weather, but none of those associations has held up.

The real question from the whole topic of hyperglycemic memory and some other things I’ve posted is this: given the evidence that hyperglycemic memory of high blood sugar decades ago can cause complications now even in the presence of perfect blood sugar control, given the evidence that much of the development of complications is determined by genetics, plus the evidence of a continuing autoimmunity in diabetics which continues to cause neurological and vascular complications in addition to the initial beta cell destruction, and the further evidence that hypoglycemia itself is damaging to the cardiovascular system, how much value is there to the enormous and potentially lethal effort to achieve strict control? Is it really worth it?

Some research now suggests that strict control may be worthwhile for new patients to delay, diminish, or postpone future hyperglycemic memory, but that once it has developed, strict control may be much less useful.

Its an interesting question that you raise. ‘Strict control’ calls up a couple of parallel, interesting questions. I think you should post your data. People will say all sorts of thing about it and challenge you on lots of mundane stuff, but someone might say something smart. Someone might have seen system behavior like this before. Worth a try.