Meta Study: Long-term Glycemic Variability and Risk of Adverse Outcomes

This solid meta-study does a fairly thorough review of existing evidence as of 2015 and correlates glycemic variability with complications. It is a 2015 study but I just became aware of it.

Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

CONCLUSIONS HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.

Interestingly, it contradicts the conclusion of @TiaG’s 2017 thread:

When I look at the two studies, the primary difference I see is that the 2017 study looks specifically at T1Ds and at microvascular outcomes, and uses the 1993 DCCT data, which is not reflective of modern treatment. The 2015 study reviews 20 publications, across both T1 and T2s, and looks at all complications, but the data across all studies is not always consistent.

[EDIT] @Katers87 and @TiaG point out that the measure of variability is different: the 2015 study looks at HbA1c variability, where the 2017 study looks at day-to-day variability. See commwents below.

I think the one you linked looked at HbA1c variability whereas the one TiaG linked looks at variability in the 7 point glucose profile.

I need to look a bit more closely though.


but this is long-term variability, not what we consider glycemic variability, the day-to-day. Bottom line is if your A1C fluctuates from 5.6 to 11.5, that’s bad for you. If your BG is fluctuating from 55 mg/DL to 300 mg/DL but you always have an A1C of 7.0, that’s not been demonstrated to be bad.



It is. But don’t you think that the two are tightly linked? I mean that in their consequences.

no, I actually am not certain of that. I mean, the few studies that have looked at the consequences of day-to-day glycemic variability have failed to find an effect while the effect of long-term variability has been shown in different places. And my son, for instance, might oscillate between 50 and 300 on any given day (today he went from 350 to LOW because no one was responding to my texts), but his A1C has never been above 7.5 or below 6.5, so he has quite a stable A1C. So he would be lumped into the “low glycemic variability” group according to the DCCT analysis. But with an SD of 50 to 60, he’d be lumped into high day-to-day glycemic variability. In other words, I’m not certain these are the same groups of people.

Of course, someone with an SD of 25 is probably also not running A1Cs that vary between 6 and 11 – but I would imagine there are actually several groups
a) Those with low SD and low stable A1C – lowest risk
b) Those with low A1c and high SD, but stable – risk level???
c) Those with fluctuating low-to-high A1C and high SD – higher risk
d) Those with high but stable A1C and high SD – high risk
e) People with low SD and fluctuating A1C – Are these real people?? (probably not) – risk level ???

And maybe all these groups have different risk profiles that don’t reveal themselves in these studies.


My early shots days, no CGM, I had A1C’s in the mid to upper 5’s but I know I had huge daily variability. I wish I knew my current A1C since FUDding (my endo forgot to order it last month but tested everything else!) but based on Dexcom my SD is much better than it was…but my average bg is higher than those earlier days.

I would be curious to know which is a better scenario long term, but I imagine it would be hard to pin down all of the contributing factors to people’s health to answer that. I believe I’m caring for myself better with an eye on the long-term now compared to my old methods despite currently having a comparatively higher A1C. Maybe not, but I think so.


Normal A1c is 5.5. Normal SD is about 20-25. Isn’t the objective to be as close to normal as possible? Doesn’t this help to normalize risk factors?

Is it any more complicated that understanding that the disease is NOT diabetes, it is high blood sugar?

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Is it any more complicated that understanding that the disease is NOT diabetes, it is high blood sugar?

I just fundamentally disagree with this. If this were the case, then people with T2 would have the same rates of complications as people with T1 for the same A1C and SD. That’s not the case.

The disease is an autoimmune response that sets off a cascade of changes in the body; one of the big factors is elevated blood sugar but there are many others tht cannot be mitigated by perfect blood sugar control, in my opinion. Of course, I concede that’s a hypothesis – but so is the notion that the disease is only high blood sugar – and that latter hypothesis has some evidence not in its favor.

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What else do you have control over, besides BG, diet, and exercise?

Why not focus on the parts you can actually control?

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@TiaG I humbly have to disagree with you, concerning the current state of knowledge, and in the daily control of diabetes. Right now I think it’s pretty well understood and practiced that the best way to mitigate your risk of complication is to maintain a normal blood sugar.

Millions ( probably billions) of dollars have been spent and companies built on the business of normalizing blood sugar levels. Forums, such as this one, have been formed to assist people who want to have normal blood sugar.

So while maintaining normal blood sugar may not be the only factor in avoiding complications, it is the most important and actionable variable. You are correct that in some cases this may not work, but our improvement in mortality and morbidity as average control has gotten better proves that it is true in the majority of cases.

Don’t forget normalizing blood pressure and cholesterol.

Just as important, if not more so in the case of blood pressure, as normalizing blood sugar.

One issue that has not been researched much is autoimmunity in and of itself, especially for the 1/3 of people with Type 1 who have more than one autoimmune condition. It’s known that immune system activation causes increased inflammation, and it’s known that some other autoimmune conditions carry a greater risk of things like cardiovascular disease. So it would not surprise me if there were subgroups within the T1D population (such as those with multiple autoimmune conditions) who have different risk profiles than the rest.

But yeah, in terms of actionable items, blood sugar, blood pressure, cholesterol control; diet, exercise, stress management; and reducing other risk factors such as weight, drinking, and smoking are about all you can do at this point in science.


I’m not saying not to focus on BG control or diet and exercise; this was only in relation to the original question on whether long-term glycemic variability is the same as short-term glycemic variability. In this instance, what I’m quibbling with is @docslotnick’s statement that the objective is to be as close to normal standard deviation as a goal. I mean, sure, as a goal – but if, for instance, the choice is between allowing Samson to eat a normal diet and having higher SD and having Samson eat a low-carb diet and achieve a lower SD, or alternatively, say, having Samson have an incredibly routine day-to-day with no exercise and low variability or dealing with more swings as a result of exercise and varying activity levels – then I’m not sure the scales tip in favor of the latter two options, in terms of evidence for benefit. We assume that’s the case, but we don’t know.

So all I’m saying is that there’s a lot we don’t understand about complication risk and that I personally am only worried about getting the numbers to a state that has actually been demonstrated to reduce complications, unless it is easy/feasible/beneficial to get down to that normoglycemic SD and BG. There have been no studies demonstrating that T1Ds who get down to an A1C of 5.5 and an SD of 25 have normalized risk relative to someone with an A1C of 6 and SD of 45, for instance, because it simply has not been possible at scale. At this point it’s a hypothesis. I’d just want to wait on evidence before I make the tighter numbers a goal to the exclusion of others.

For instance,I could probably have Samson maintain an A1C of sub-6.0 if I kept him out of school and made him do the same exact things every day, hired a nurse to micromanage his blood sugar at night, ignored my other sons, etc. And you know, if strong evidence told me this would lower his risk to exactly that of a normal, healthy person without any kind of diabetes I might think twice about that option. But I don’t think that makes sense.


This is exactly why I abandoned low-carb. I think that if I’d only had diabetes, I would have kept going, but for me currently it was just too hard, and I had no evidence that it was actually going to help in the long run.

I hope that at some poine they do manage to do a study of people with T1D with super tight control, with or without following a low-carb diet. Because if I knew for sure that aiming for a target A1c of 5.5% instead of 6.0-6.5% and an SD of 25 instead of 50 were going to help me, then I would do it no question. But I just can’t justify so much effort (at least right now) based on an unproven hypothesis.


Maybe not at this young age, but at some point he can have an A1C less than 6.0 without doing all of that stuff.

I don’t think you have to eat low carb and have a strict diet and an unchanging routine to do all that. I certainly don’t live that way.

It is possible to live free and still have great numbers. But that also will take a while for him to get to a certain age.

I have never understood the A1C as a target. You try to have the best BG, and try to manage it as well as possible.

How does it change your daily care?

I don’t need to take as much insulin for this meal, because I am currently ahead of my target this month…

I don’t think of the A1C as a goal, it is just the validation of the daily routine. I did well, or I didn’t do as well as last time, what’s working, what isn’t working, etc.

Every meal you try your best. Every night and every day, you always try your best. You always try to have the best BG. And as the A1C gets lower, you see the results of your effort. You know you are on the right track.

Anyway, that’s how I would encourage people to use the A1C number.


Every meal you try your best. Every night and every day, you always try your best. You always try to have the best BG. And as the A1C gets lower, you see the results of your effort. You know you are on the right track.

So this is how we try to do things and very much how I think of things on a good day. But the reality is that Samson has two caregivers at home and four to six caregivers at school, Not all of them are always trying their best, and diplomatically speaking, some of those peoples’ best is still quite lacking. Not to mention that we’ve had so.many.problems with the G6 that leads to data drop-outs for a few hours almost every night – and of course it’s always when it counts. So right now, we as parents are not pushing ever harder to lower his average BG, keep him steadier, etc… so much as we are trying to put out fires at school for instance, dealing with poor and delayed communication with an ever-changing tableau of teachers, reinventing the wheel as we continually tweak the care protocols to make things easier for him, figuring out how to navigate around unreliable sensors, and struggling with crummy WiFi problems that knock openAPS out randomly.

We’re in a state of stagnation right now; that’s not great but what I’m saying is that at this point, we’re sort of okay with treading water because I see his A1C is okay, and I tell myself “this number is telling me we are doing an adequate job for now – when things settle down or he gets older or circumstances change for the better, we will start pushing for that continual improvement again.” If there was stronger evidence that a super low A1C could erase all his risk of complications though, I probably would start thinking really outside the box and not be okay with this treading water right now, even for another 9 months. (Maybe I’d take him out of school or attach two different types of sensors to him, change his diet, etc. etc…) Given all these external sources of variability, we aren’t keeping super tight tabs at every meal, documenting every bolus for inspection, making absolutely sure he carries his phone with him at all time, or even going over Samson’s numbers and settings every week like we used to.

That’s not ideal of course, but the fact is that A1C is the only measurement that’s been well established to be correlated with complication risk, so it’s a reassuring number that tells us we’re doing okay for the time being – that it’s okay to mentally take a breather on that “better and better and better” attitude for a second while we catch our breath.


15 posts were split to a new topic: Should diabetes treatment optimize glycemic variability?

I’d say this is a YDMV statement, very respectfully.

Even WITH doing most of those things mentioned everyday religiously for years, I haven’t been able to crack sub-6. I’m just thrilled under 7.0 right now. But you all know my stance on the difference between T1D for women compared to T1D for men, and the comparatively infinitesimal amount of scientific knowledge we have about insulin sensitivity variability on a daily basis for women. Obviously this doesn’t apply to Samson for your point, but results don’t always reflect effort.

My Safety Rating, if there were such a thing…I guess SD is close to that idea, is much much better than it was when I actually was sub-6.

Being Unlimited looks different for me today than when I was in early diagnosis. I’m okay with that. Weighing it all out, acute safety is my top goal, followed by quality of life, then long-term outcomes. And the third one is a big unknown so we’ll see what happens.


Thanks. I was going to say exactly this.

Whether the goal is an A1c of sub-6.0, or a standard deviation of 25, or spending >75% in target range, or not having daily lows, these targets still elude me.

I’m not sure whether there’s still something I’m missing that other people are doing, or whether I should just settle on my current level of control as “good enough” and wait for a closed-loop system to come along.


Sub 6 - is elusive for most people, I wouldn’t beat yourself up to much about that. Of course the closed-loops systems offer some promise, but I would think a sub-6 closed loop is still a ways off for most. It should increase your time in range however.


Yeah, I think just because sub-6 is doable for some folks without extreme measures, doesn’t mean it is for others. @Eric, some of what goes into your control for example, like high levels of regular exercise, is simply not possible for other people (for example, due to my connective tissue disorder, most exercise is off limits to me, and what I can do, I have to do extremely carefully and often with breaks to manage subluxations and/or injuries). Also, I think it’s notable that the majority of people I’ve seen on the forums with super tight control who do NOT engage in very low carb diets etc are either adult men or post-menopausal women with few or no co-morbid health conditions. When you have multiple other conditions and/or cycling hormones in play, you’re really dealing with a different disease in many respects than someone who doesn’t, and the same rules often just don’t apply.