March 17, 2008

More Insight into Why A1c Doesn't Match Your Meter Measurements

My book is at the printer and the house is finally clean. I am not constitutionally capable of writing books and cleaning bathrooms at the same time, so when a book is finally done, the next thing I have to do is get scrubbing. Now back to blogging!

I found an interesting editorial in an issue of Diabetes Care published last year that pointed me to a couple research studies that have a lot more to contribute to our understanding of how well the A1c test result correlates to measurements of blood glucose.

Here's the article. A1c Does One Size Fit All? By Robert M. Cohen, MD.

Cohen states that his own work found that, in a small group of Type 1s, when they compared a simultaneously drawn fructosamine (FA) test and an A1c test "23% of subjects had A1C >1 percentage point higher and 17% had A1C >1 percentage point lower than the value predicted from simultaneously drawn glycated serum proteins." [i.e. a Fructosamine test]

Cohen explains that the FA is more closely correlated to blood glucose levels than the A1c.

More interestingly, for individuals, the gap between the two measures stayed constant over time when the test was repeated. So if the A1c was lower than expected once, it would be lower by a similar amount on subsequent testing.

Cohen then cites another study from his lab saying, "Our laboratory showed data demonstrating, with a new highly precise technique for red cell survival determination, that much more variation in A1C in hematologically normal people can be explained by differences in the mean age of circulating red cells than is currently appreciated."

He adds, "We have also shown data suggesting interindividual differences in how the steady-state concentration of sugar in the red cell relative to that outside the red cell relates to differences in the level of hemoglobin glycation". Which means that different people have red blood cells that will glycosylate at different blood sugar concentrations.

So these findings confirm that no, you are not alone when your A1c doesn't match your measured glucose, test after test. Forty percent of people will read 1% higher or lower than expected according to Cohen's data. He estimates that there are Three Million people in the U.S. whose A1cs don't match their measured blood glucose.

Cohen then cites a new study that found that when non-white populations were studied, the A1c was found to be even more likely not to match predictions based on measuring blood glucose.

Quoting Cohen again, "A1C was consistently lower in whites than in any of the other groups."

The difference was greatest in Black people whose average A1c was almost .5% higher than that of whites. Cohen points out that the DCCT and UKPDS both studied almost entirely white populations, making this a very significant finding.

The zillion dollar question is: which matters most, A1c or measured blood sugar?

We have seen that with neuropathy, in people with prediabetes there is no relationship between a person's A1c and the incidence of neuropathy but there IS a relationship between their 2 hour Glucose Tolerance Test result and the likelihood of neuropathy. This points pretty clearly to the conclusion that it is the post-meal spikes, rather than average blood sugar of any type that causes complications.

Cohen's study of Type 1s found that when A1c was higher than the value predicted by the Fructosamine test there was a tendency to have more kidney problems, though he states that it is possible that poor kidney function might be responsible for the gap, not the other way around.

But the fact remains that because researchers rarely measure post-meal blood sugars in the free range person with diabetes, we don't know where to point the finger: A1c or post-meal spikes?

The Glucose Tolerance Test (GTT) doesn't really duplicate the kind of blood sugar you will see day in and day out your after meals. If you have any insulin production capability left, when you take an Glucose Tolerance Test you are likely to see higher one hour highs and lower two hour values on the GTT than you see when you eat real food.

Wen you eat real food, your blood sugar is likely to climb more slowly and stay high longer, because of the speed of digestion and the impact of simultaneously eaten fat and protein on that speed. If it is a couple hours of exposure to a blood sugar of, say 150 mg/dl, a person with marginal blood sugar control might get that damaging exposure eating a bagel with cream cheese, but not see that 150 mg/dl as the 2 hour value on a glucose tolerance test.

Another thing that sheds light on the question, "Which matters, the A1c or the post-meal blood sugar?" is one large study, the Kumamoto Study, which found that a group of Japanese people who get an average 7% A1c by limiting their post-meal blood sugar spikes got far fewer complications than did the group of people in the UKDPS study who got the same average 7% A1c but made no attempt to limit post meal spikes.

The study Cohen cited suggests that Asian people's average A1cs were .16% higher than Whites (meaning that that if the White Average was 5% the Asian would be 5.16%) , which may suggest that the Japanese group's 7% A1c reflected a slightly lower blood glucose level than the White group's 7%. But even so, the difference probably isn't enough to explain the far more significant decrease in complications seen in the Japanese study compared to the UK study.

For now, I'm betting that it is those post-meal spikes causing the mischief. But because of the cost of testing, we aren't likely to see any large-scale studies where the complication profiles of people adhering to stringent post-meal blood sugar goals like the 140 mg/dl AACE 2 hour goal are compared to those with looser goals--like the ADA's anemic 180 mg/dl 2 hour goal.

What I do know is that, since the complications that matter to me are the ones I get, I'm going to be a lot better off if I go for the most stringent goal. Beyond that, if the A1c is the problem, past a certain point, there isn't a darn thing I can do. I can lower my post meal blood sugars but no matter how much they drop, since I started cutting back on carbohydrates, my A1c is always about .5% higher than predicted. Oddly, in the past when I was eating a lot of carbs,it was always lower than predicted from blood sugar measurements. This might point to yet another factor that isn't ever going to be researched.

What a complicated mess all this blood sugar stuff is, eh?


Anonymous said...

From reading your and other material (confirmed now with this last article)I have been telling my friends that they should every year or two eat a moderately high carby meal and do a two hour check. Sure wish I had over these last ten years. RobLL

Anonymous said...

In a dark corner of my mind, I remember reading that glycosated haemoglobin is reversible provided that the BG dips quick enough following the initial bonding of glucose to the protein. So if you minimise the post prandial spikes, maybe you can un glycosate some of your newly glycosated haemoglobin.

Further, maybe low GI carbs might not then be such a good thing relative to high GI carbs??


Jenny said...


I am not a fan of "low GI carbs" for anyone except someone who still has a very strong second phase insulin response or who is using insulin (which simulates 2nd phase insulin response).

The glucose from the so-called low glycemic foods still hits the blood stream and it still has to be removed by insulin.

The GI was determined by testing normal people who have both a first and second phase insulin response. People with diabetes have no 1st phase and often very little 2nd phase release left.

Anonymous said...

" The glucose from the so-called low glycemic foods still hits the blood stream and it still has to be removed by insulin."

Therefore low GI gives an extended period of higher than desirable BG, which would then prevent newly glycosated Hb from losing its sugar coating before it becomes permanent for the life of the red blood cell. Either way I agree that low and high GI carbs are bad for subsceptible individuals like me.


Tyler said...

Is there any research on how macronutrient composition of the diet influences red blood cell life span? I am wondering if it is possible that low-carb diets increase red blood cell life span in some people, as Jenny sort of alluded to.

Jenny said...


There is very little research about the low carb diet, period, and too much of it is done to prove things the researcher has concluded are true before running the study. (Both pro and against.)

There are plenty of people eating low carb who get low A1cs and then people like myself who can eat perfectly and keep blood sugars completely flat and still see higher than expected values. So my guess is that it may be gene variations at work too.

v/vmary said...

" when you take an Glucose Tolerance Test you are likely to see higher one hour highs and lower two hour values on the GTT than you see when you eat real food."

i am wondering if people who have been eating low carb should even 'carb up' as a way to prepare for the 2 hr OGTT, as is usually recommended. if the point is to get the endocrinologist to take you seriously, then don't carb up for the test so you put up even higher BG numbers so they will start you on metformin instead of waiting around. do you agree?

Jenny said...

Good point. It definitely does depend on why you are taking the test. If your post-meal numbers are too high without a stringent diet and you would like your doctor to give you some help, not carbing up might help, though it won't make a huge difference in your readings.