Researchers Suggest Adjusting the Glucose Level We Think of as Hypoglycemia

The researchers suggest that if hypoglycemia is to be defined by a predetermined glucose level, then the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the ADA.

Sep 29, 2008

An article published in Diabetologia this month challenges the accepted glucose cut-off values that define hypoglycemia because they have a major effect on reported frequencies of hypoglycemia.

Researchers set out to quantify the relationship between the frequency of hypoglycemia and various glucose cut-off points for the definition of hypoglycemia, within a range of A1c strata.

Data from two trials examining insulin glargine dose titration in 12,837 type 2 participants with diabetes starting insulin therapy were combined. Curves for hypoglycemia frequency plotted against endpoint A1c level were constructed, using a range of glucose cut-off points for hypoglycemia.

During the 12-week study period, 3,912 patients recorded 21,592 hypoglycemic episodes, which were classified as either "severe," "symptomatic," or "asymptomatic" events. 

The researchers concluded that the glucose cut-off point defining hypoglycemia greatly affects the reported frequency of hypoglycemia. In order to have clinical relevance, and if hypoglycemia is to be defined by a predetermined glucose level, then the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the American Diabetes Association.

Read the journal article here.

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Posted by Anonymous on 30 September 2008

..."3.9 mmol/l"...

But what is this in mg/d? That's how I measure my blood glucose. Articles that only give one or the other measurement aren't as helpful as they could be.

Posted by mjensentulsa on 30 September 2008

Don't you love them scientists? They're talking about redefining hypoglycemia from 70 mg/dl (that's 3.9 mmol/L) to about 58 mg/dl (3.1 mmol/l), so they can have a better idea of what "real" hypoglycemia is.

The only problem is, for those of use with "real" diabetes, a reading of 70 can be a serious danger signal, and not acting until you get a reading of 58 (when? an hour later? three hours? six? Too late -- your seized!) can mean a lot more than the "clinical relevance" they seem to be concerned about.

The focus on A1c's may be the culprit here. Everyone wants to get their A1c's down -- the scientists, the drug sellers, the doctors and, of course, we patients. But at what cost?

I'm as worried about complications down the road as the next Type 1, but I also have put my family through a number of episodes where I just didn't walk that tightrope carefully enough. Luckily, it usually happens at night when I'm asleep. To some people, it can happen (asymptomatically) when they are quite literally driving down the road.

Who is counting those "complications" I wonder?

The doctor thinks you should cheer when your meter reads 90. All I can think is, "which way is this headed? How much can I trust it? When should I test again?" Remember that the reading can be off, in either direction, by 15% or more.

The researchers DID take the patient's balancing act into account, but not necessarily to our benefit:

"Higher cut-offs identified more patients having severe hypoglycaemia, but this was at the expense of the specificity, i.e. a very large number of patients that did not experience severe hypoglycaemic episodes were also labelled as ‘at risk’."

In other words, they were disappointed by those who successfully crossed the tightrope, day after day, when the target is set at 70. They want to exclude those folks from being categorized as "at risk" so they can more accurately predict the number of falling bodies.

The redefining of hypoglycemia has a lot of implications beyond the laboratory, and any redefinition should take this into account. The publishers deserve a sharp rebuke for not adding any disclaimer to the acute physical danger of putting more people into that risk category they so blithely redefined.

Shooting for 58 can be fatal.

Posted by Shockmaindave on 30 September 2008

And in other news, the US Federal Government cut the number of people living in poverty nationwide by 98% by redefining poverty as "having an income of at least $200/year."

You have to love the second-to-last paragraph's disclaimer that this work wouldn't really apply to Type I patients and that further studies must be done on this group. That is undoubtedly true: They would be able to find out just how dangerous these results would be for Type I diabetics.

I hope this study isn't taken out of context. I would never go to bed with a blood sugar of 59-70. I'm not sure telling my wife "I'm not having an insulin reaction"--which would probably come out "inssslinreacssshin"--because I read it in a journal" would pass muster with her.

Posted by HOFIII on 1 October 2008

For the reader that responsded 1st, you take the mmol reading and multiply it by 18 to get the mg given by your meter. For example, a 3.9mmol X 18 = 70.2mg (or a meter reading of approx. 70)

You can also take a A1c (for example) of 6.0 and multiply it by 18 and get the average BG over the 3 month period. example: 6.0 X 18 is an average BG meter reading of 108 over the past 3 months. Hope this helps!

Posted by cde on 1 October 2008

While 55.8 mg/dL is NOT fatal for any child or adult, it can be uncomfortable for some persons. Frequent BG monitoring makes it possible to prevent anything in the "low" range set by the individual's tolerance/comfort level from occurring. In this way, each person tends to define hypoglycemia according to his or her tastes and meter measurements.

This is a complicated issue, inasmuch as "normal" children (wihtout DM) have (up to 35% of the time, in the fasting state) very low, truly hypoglycemic BG...and do so without symptoms or discomfort.

I agree that the question of at what level we can factually (with respect to BG reality in persons without treated DM) say that a person has hypoglycemia is not yet answered.

As I understand the study referred to, the researchers' idea is that hypoglycemia is somewhat lower than we are accustomed to thinking it is. It never hurts to know what is reality, but changes to our belief system do often hurt or produce resistance.

But how to define the reality of hypoglycemia? Is it necessary to have a numeric definition for those who have DM different from that used for those who do not have DM? Are adults and children "hypoglycemic" at the same or different levels? Are boys' and girls' BG pretty much the same? Do African Americans' and Caucasians' BG correlate well or closely?

Do hypoglycemic episodes classified as either "severe," "symptomatic," or "asymptomatic" events have an associated BG? Or is "symptomatic" hypoglycemia solely defined at the discretion of the person who experiences it?

Dr. Stan De Loach
Mexico, D. F.

Posted by banniaa on 5 October 2008

I'm not a diabetic, but a reactive hypoglycemic so I'm kind of out of my league here. But I do have something to say here. I have to follow pretty much the same diet of a diabetic. Depending on why I'm at 70 is a big deal. Did I not eat in time and my BG is fallng, or did something I eat have a sugar, simple carbs or something that I react to and it's only been an hour since I ate. That's a big deal, and I have got to find food pretty quickly. I prescribe to the idea that it's not necessarily where you're at on the BG scale (although that does really matter as it goes lower) but how fast it is moving in that negative direction. That fast drop makes you feel pretty bad, even if you are not at 70 yet.

Posted by fatfaria on 6 October 2008

Drawing on my experience of 38+ years of T1 DM what I found out was that the lower I bring my A1c the lower the cut-off point of disconfort when hypo's occur. The same applies to the sensation of thirst when BG is high. I now have the sensation of thirst at much lower BG levels when my BG is not in check.
To lower the risk of asymptomatic hypo's I try to stay within a margin of confort with my A1c's, ie in the range 6.5-7. In order to go below that I have to enter the danger zone way too much too many times!

F Faria, Portugal.

Posted by mjensentulsa on 7 October 2008

In response to cde ("Dr. Stan De Loach"), who observed "55.8 mg/dL is NOT fatal for any child or adult."

The point I was making, from a diabetic's perspective has clearly been missed here. When I said "Shooting for 58 can be fatal," I was not saying that a bg of 58 will kill you, but rather that defining hypoglycemia at such a low point will result in an increase in fatalities, due largely to the inaccuracy of Dr. De Loach's next comment, namely that "Frequent BG monitoring makes it possible to prevent anything in the 'low' range set by the individual's tolerance/comfort level from occurring."

In fact, even with frequent testing (what does that mean? 6x per day? 8x?), there will still be an average of three or four hours between samples. So, if, for instance, a test result is 62 (within the current definition of a hypo, but in the new "no risk" zone according to the proposed redefinition), the actual value could be 15% less due to testing error (which means the actual BG could be as low as 53 -- oops!). Then you've got a starting point of 53, with 3 or 4 hours for that number to slide.

Other research suggests that the "comfort level" issue is itself a dangerous myth among clinicians. The phenomenon of asymptomatic hypoglycemia has been poorly understood, but I and other diabetics have long suspected it to be a "slope of the curve" issue -- it's not the bg number that brings on the symptoms, but the rate of change of bg.

This suggestion is affirmed by banniaa, who comments, "it's not necessarily where you're at on the BG scale...but how fast it is moving in that negative direction. That fast drop makes you feel pretty bad, even if you are not at 70 yet"

The medical community may be coming around to this perspective, though I haven't seen any specific research that confirms it (see "Alternate Theory" at ).

The point that I am emphatically trying to make here is that neither researchers nor clinicians seem to "get" how dangerous their recommendations are, when they base them on statistics rather than experience; by averages rather than outliers. Of course a BG of 58 will not kill you! But if you don't treat a meter reading of 62 as hypoglycemia, then the drop from what it truly is (53) within the next 3-4 hours (slowly sinking, asymptomatically, to 40 to 30 to 20) can kill you. Especially if you're driving a car, or swimming in a lake, or sleeping in a hotel room alone.

Even if you discount those fatalities (how many in a year, a few hundred? a thousand?), you also have the zap factor: The patients you recommend such overly aggressive tactics to will, eventually, learn not to go back to that live-wire.

You tell them to lower their A1c to 7, to 6, or lower...and just a handful of severe hypos can convince them that it's just not worth it.

The net result is less control, worse outcomes and reduced quality of life, thanks to the reality-free recommendations of the clinical community.

Posted by Shockmaindave on 7 October 2008

My uncle and I (both Type 1's) used to play a game called Blood Sugar Blackjack. The goal was to get our blood sugars to 21 without symptoms. The key, of course, is to ease down slowly. Too quick a drop would make our wives notice we were playing again, which would result in an immediate disqualification.

We ultimately stopped playing, not because of the risk of brain damage, but because of a philosophical disagreement regarding whether one was winning or losing the closer he got to 21.

Trying to define an insulin reaction with a number is like trying to appreciate the Mona Lisa by looking at RAW Photoshop data. Look instead at what Justice Potter Stewart wrote about obscenity: "I know it when I see it..."

Any one of the 3,912 Type II diabetics surveyed in this study--and please understand my prejudice against Type IIs as diabetic wannabees--could have told the doctors writing this study that there is far more to diabetes management than absolute, numeric definitions of hypoglycemia.

Even so, no diabetic doctor that I know is going to sit still on a 68 blood sugar because the authors of this study have suggested it's possible to do so. Nor would any diabetic. Except maybe my uncle and me.

Posted by cde on 8 October 2008

Human languange is inadequately able to convey complex, personal, emotionally-charged matters. And DM self-treatment is one of such matters.

To be clear, I am ONLY referring to self-management of DM1 in what I write. DM2 is another condition about which I rarely write and about which I know somewhat less than I know about DM1.

In DM1 self-treatment (and I contend that no one but the person with DM can treat his or her own DM), what works is defined by one's goals. What works is decided by experience, over longer or shorter time periods.

All we as health care professionals offer is advice, suggestions, ideas, tips, clues, information, education. The person with DM takes or rejects, applies or does not apply, the information offered, in order to see if it "works" for her or him.

"Works" means that something contributes in a positive way to the achievement of one's individual glycemic and lifestyle goals as a person with DM.

For me, and partly in reply to mjensentulsa, "Frequent BG monitoring [does indeed] make it possible to prevent anything in the 'low' [glycemic] range set by the individual's tolerance/comfort level from occurring."

Frequent testing is defined by the individual with DM. For me it might be 12 times a day that is effective in avoiding hypoglycemia AND hyperglycemia (my personal goal, for example). Another person might only be interested in avoiding hypoglycemia, which, unlike hyperglycemia, is more likely to have symptoms or to produces signs.

For a variety of reasons (type of insulins used, frequency of food intake, timing and intensitiy of physical activity, and others), each person with DM has to decide how often he or she requires BG testing. This is decided in the best of cases not by the physician or CDE, but by the person herself or himself, in consultation with the physician and CDE, taking into account also his or her own previous personal experience with BG measurement.

How to decide? By what works, that is, what enables me to achieve my goals. The goal may be a "walking on the wild side" or suicide [BG 21...I learn something every day!] or avoiding hypoglycemic symptoms or an A1c of less than 7% or correlating physical states with BG values...or any other.

If I take ultrarrapid insulin before eating and I want to avoid hypoglycemia of 58 mg/dL, I may decide to check BG at 75 minutes after the first bite of each meal, for example. This might work or it might not work; only experience will tell. And the learning may only be valid until the next change in insulin dose, insulin type, meal composition, meal quantity, etc., at which point the experiential learning curve may need to start anew.

How long between BG measurements? Learning from experience that one never has hypoglycemia after breakfast may mean that the ultrarrapid insulin dose before breakfast is either correct or insufficient. Or that the content of breakfast is in accord with my attempts to attain this goal.

Actually, a self-monitored BG test result of 62 mg/dL, it is true, could be an actual value 0-15% LESS or 0-15% MORE, due not only to testing error but also to the permitted-by-government-standard allowance inbuilt in the BG meters themselves.

So the actual BG in this case could be as low as 53 mg/dL (hypoglycemia) BUT it could also be as high as 71.2 mg/dL (not hypoglycemia but almost so, depending on one's personal definition of hypoglycemia). What is known from this reading is that my blood glucose is between 53 and 71 mg/dL.

So checking, and finding this result, would permit limited glucose intake in order to avoid continued hypoglycemia or to avoid a further "fall" in glycemic levels. If the goal is to have rebound hyperglycemia, glucose intake to treat this mild hypoglycemia would be practically unlimited.

Confusion sometimes occurs because we say "hypoglycemia," without further ado. In fact, there are three types of hypoglycemia:

therapeutic (normally a value < 70-71 mg/dL, at which point one TREATS the hypoglycemia with glucose but more importantly uses it as a reference point for the adjustment of insulin dose and/or food quantities or content and/or physical that this level of glycemia is avoided in the long term)

clinical (indicated by "symptoms" or manifestations of physiological glucose deficit; clinical hypoglycemia may but does not always require glucose intake because it also appears when there is a major fall in BG levels, from 250 to 100 mg/dL [for example] in a short time. BG measurement is essential to distinguish the cause of clinical hypoglycemia, which may also be "true" hypoglycemia)

biochemical (a BG concentration of less than 55-50 mg/dL, with or without hypoglycemic symptoms or signs).

For those who use ultrarrapid insulins that cause BG to drop quickly in the absence of a corresponding correct amount of glucose, the rate or frequency of BG measurement will logically be higher, though logic can be overriden at any point by the decisions the person makes.

The purpose of BG measurement is to facilitate self-treatment decisions. What one does with a given value is critical and the measurement of BG value is key in the self-treatment decision.

Why would one decide NOT to treat a meter reading of 62 mg/dL as hypoglycemia? If her or his target range is 71-99 mg/dl, for example, a decision not to treat with glucose would be a decision to invite a further drop in glycemia.

These types of dialogues are appropriate (and interesting and exciting!) for visits with the MD and CDE because they genuinely help everyone involved to take thought about what and how we self-manage DM and set our self-treatment goals.

Posted by jkaptena on 2 January 2010

Hypoglycemia varies from one diabetic to another just as the treatment varies from one T1 to another. I am a T1 for 39 yrs. I now have hypo unawareness. After being a T1 for several yrs has resulted in having no warning signs before a low. I check BS before eating & 1 hr after eating and again at 2 hrs after eating. I am on an insulin pump. My BS can be 178 2 hrs. after eating and drop to 60 within 30 minutes. Once it starts to drop it varies from diabetic to diabetic on how fast it will drop. A BS of 75 and dropping quickly can be fatal for some diabetics. Dropping the range for lows is ridiculous and especially dangerous for brittle diabetics as well as for all diabetics. Many insurance companies even with the current range for hypos refuse to cover glucagon and tell me that I should be able to chew glucose tablets while unconcsious. It is vital that the ranges not be lowered if only to allow for T1s to be able to access the medical care needed.

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