October 30, 2009

Does 5.5 A1c Predict Retinopathy?

A new, high quality study which I cited in my Updates to Blood Sugar 101 blog found a steep increase in the incidence of retinopathy in people not diagnosed with diabetes whose A1cs were 5.5% or more. The study found that the predictive value of the A1c was much stronger than the predictive value of fasting blood sugars in the same population.

At first glance this might be a very disturbing finding to those of us who find it difficult if not impossible to lower our A1cs below 5.5%. I have not been able to do this even when eating a very low carb diet. My A1cs are almost always between 5.7% and 5.8%.

I've discussed why some of us have higher than expected A1cs in another blog post.

But I want to raise another point here, one that is often lost when researchers use A1c:

The A1c reflects average blood sugar values over time, but there are many ways to attain an average.

In fact, what the A1c really measures the amount of glucose that has gotten bonded onto red blood cells over a period of time. The more exposure red blood cells have to high blood sugars, the more glucose they accumulate. Since these red blood cells live about 3 months, the A1c is supposed to reflect three month's worth of blood sugar exposure. In reality, though, the A1c reflects the several weeks right before the test, much more than it does the whole three month period.

Studies that compare CGMS readings with A1cs conclude that that A1c gives a close approximation to average blood sugars for a population as a whole, and much rougher approximations for the average blood sugar of the individuals in a population.

Note, however, that people with unusually high or low concentrations of red blood cells will get A1c readings that do not reflect the actual concentration of glucose in their blood. So will people whose red blood cells have longer than normal lives and those with certain genetic oddities that affect their red blood cells' ability to bond to glucose.

But even in people with absolutely typical red blood cells, two people with the identical A1c can achieve those A1cs while experiencing very different patterns of daily blood sugar fluctuation.

For example, a 7% A1c has been most recently equated with an average blood sugar of 155 mg/dl (8.6 mmol/L). A person can achieve this average by maintaining blood sugars that oscillate between 85 mg/dl (4.7 mmol/L) before meals and 225 mg/dl (12.5 mmol/L) after meals or they can get the same A1c by maintaining a blood sugar that oscillates between 130 mg/dl (7.2 mmol/L) and 180 mg/dl (10 mmol/L). Depending on which pattern they follow, the likelihood of developing diabetic complications is very different.

This was clearly demonstrated by the comparison of two studies--the UKPDS and the Kumamoto Study--where participants had the same 7% A1c but very different complication profiles because their post-meal blood sugars were very different. You can find the citations to the comparison of these studies HERE.

So before we panic about the finding that as A1cs go over 5.5% the incidence of retinopathy spikes upward, we need to give some thought to what the underlying blood sugar fluctuations might have been of the people with 5.5% and greater A1cs in this population.

An A1c of 5.5% corresponds (in large populations) with an average blood sugar of 112 mg/dl (6.2 mmol/L).

Since this group was made up of people not diagnosed with diabetes, we can make a pretty good guess at what kind of diet they were eating: One very high in carbohydrates. Remember, nutritionists consider 300 grams a day a normal carbohydrate intake.

It is likely some of these "normal people" who were prediabetic. In that case, they were likely to be experiencing very high post-meal numbers that dropped back to normal after two hours or even went low, as happens with reactive hypoglycemia. If that were true, they would be were seeing oscillations that veered between 75 and 150. The average of these two values just happens to turn out to be 112 mg/dl.

We already know that exposure to post meal blood sugar levels of 140 mg/dl (7.7 mmol/L) is associated with a rise in many different diabetic complications. So it no longer is mysterious why that 5.5% A1c might be the lower boundary after which retinopathy diagnoses start to rise steeply. Those "normal" people with the 5.5% and higher A1cs were probably eating high carbohydrate meals throughout the day and spending hours each day above that 140 mg/dl threshold that is already
documented as the level at which diabetic complications start to ramp up.

The graph showing normal people's blood sugars, which you will find HERE, shows that there is a significant proportion of "normal" people who are going up over 140 and staying there for almost 2 hours after eating their normal high carb breakfast. They are likely to do this every day and probably see similar patterns after lunch and dinner too. My guess is that it is these "normal" people who are most likely to developing diabetic complications in the prediabetic range that corresponds to A1cs at and above 5.5%.

But there is another blood sugar pattern that also leads to that 5.5% A1c--the pattern in which the blood sugar stays near 112 all day long, or perhaps where there is a relatively high fasting blood sugar--110 mg/dl, and very narrow fluctuations at meal time, perhaps up to 120 and then back down to 90.

This is the pattern characteristic of people who control their blood sugar by cutting way back on carbohydrates and using drugs like metformin and/or insulin to flatten out their blood sugar peaks. Many find that they cannot prevent higher than normal fasting blood sugars, but they can easily keep their blood sugar under 120 mg/dl after meals.

For people who achieved a 5.5% A1c--or even one slightly higher--by keeping their blood sugars under 140 mg/dl most of the time, the risk for retinopathy may well be much lower.

None of the published large scale studies links complications to post-meal blood sugars because post-meal numbers are too expensive to monitor in a large group, so it is impossible to prove this, but anecdotal reports from those of us in the online diabetes community who have kept our blood sugars under 140 mg/dl for years at a time suggest this is true.

So if you can keep your A1c under 5.5%, you can feel confident that you are doing what you need to do. If you can't, you are in the majority of people with diabetes and there is no need to panic if you keep track of your post-meal highs and keep them under 140 mg/dl as much as possible. (The technique described HERE will help you do just that.)

And if you do go high from time to time--and we ALL do--don't panic. It takes many hours spent at high blood sugar levels day after day, month after month, over a period of years that promote complications. If you spike high for an hour or two every now and then, it is not likely to cause massive damage.



jimpurdy1943@yahoo.com said...

You said:
"... people with unusually high or low concentrations of red blood cells will get A1c readings that do not reflect the actual concentration of glucose in their blood."

That's interesting. I consistently test as borderline anemic, and for that reason I have sometimes been prevented from donating blood. However, various tests. including a colonoscopy, have not found any reason for me to be anemic.

I sometimes drink a lot of tea, which apparently binds to iron and perhaps may cause anemic-like test results.

If that is correct, could heavy tea drinkers not only seem to be anemic, but could their HgbA1c test results also be misleading?

In a worst-case scenario, could my "real" blood glucose be even worse than my tested A1c?

Jenny said...


I'm pretty sure that anemia is diagnosed by counting red blood cells mechanically. If your red blood cell counts are low, it would have nothing to do with your iron levels.

And yes, anemia will lower the A1c because with fewer cells there is less glucose bonded to those in the sample.

If you are testing your blood sugar 1 and 2 hours after eating, you should have a very good idea of what your blood sugars are doing over time. If the A1c is lower (or higher) than you'd expect, then trust the meter readings.

Unknown said...

RE your assumption: "An A1c of 5.5% corresponds (in large populations) with an average blood sugar of 112 mg/dl (6.2 mmol/L).

Since this group was made up of people not diagnosed with diabetes, we can make a pretty good guess at what kind of diet they were eating: One very high in carbohydrates. Remember, nutritionists consider 300 grams a day a normal carbohydrate intake."

Largely OT and FWIW: I am not diabetic. My A1c hangs right around 5.5. My daily carb intake never approaches 30 grams let alone 300. I have been low carbing for years. My diet contains no starch and almost no sugars. Other than the occasional raspberry or tomato, the highest glycemic food I eat is eggplant. I've never had a blood glucose reading over 140, even in the throes of a meal. So, either I'm an anomaly or your assumption is off.

Jenny said...


Have you developed retinopathy?

The issue here is what makes the 5.5% A1c predictive of retinopathy in the normal population.

Beyond that, what percentage of the NHANES study subjects would you estimate were eating a very low carb diet like your? A very small portion indeed, because the low carb lifestyle is one that very few people adhere to long term in the general population.

Kathy W. said...

Jim, you might want to check your serum ferritin levels, which is an even better measure of iron deficiency.

Also, I think A1C goes up in iron deficiency (but not anemia per se) and down when the deficiency is corrected. Lab testing services mention that iron deficiency may lead to a falsely elevated A1c. Here's a study of both diabetics and nondiabetics whose A1cs dropped quite a bit when their iron deficiency was corrected:


Anonymous said...

Vitamin B12 (and I think B6) may be associated with lack of absorbtion of iron: worth testing, and you could see if you can get a fructosamine test to compare with your A1c (rarely used in humans but commonly used in animals, I wonder why?)

Yes I had endless eye inflammations and even infections from what I now know to be relatively high but short postprandial spikes followed by reactive lows, I'm surprised there was no long term damage from what was obviously a load of sorbitol concentrated my my eyes. This occurred with an A1c of 5.3 and resolved with an A1c of 5.6 mainly because the spikes were removed, but also the lows.

These sort of patterns are why spot testing is absolutely essential no matter what your Health Professionals tell you.

Nelle said...

Would having a slightly elevated hematocrit cause a high A1C? My hematocrit was a little above normal- not sure why- maybe a little dehydrated- and my A1C was 5.9. Can't understand that since my BS was consistently 69-89 random, and 94-104 two hours after a meal. Rarely up to 115 two hours after. No meds- low carb diet only.

Ed Terry said...

I've been eating low carb for a year and a half now and loving it. Up until recently I never tested above 95, even postprandially. I do donate blood four times a year because my hematocrit runs high.

Last week, just for grins, I ordered an HbA1c test, expecting the results to be around 4.8. I was shocked when it came back at 5.6! I quickly grabbed my wife's blood glucose meter and started taking regular measurements: fasting, 1 hr and 2 hr after meals. So far, my average is running at 105, which concerns me. There also doesn't seem to be a consistent pattern, even though my eating schedule doesn't vary that much and I eat pretty much the same thing day after day with the exception of supper.

I'm at a loss as to what could be causing this. I do eat every couple of hours and my net carbohydrate intake is constant at 55 g/day. On a couple of occasions this week in the afternoon, I had blood glucose levels over 150.

I do drink a significant amount of coffee so I'm thinking of moving to decaf eventually, but my coffee consumption hasn't changed significantly over the last 5 years. I've also been taking immediate-release niacin for 7 years now but was never aware of any blood sugar elevations.

Any guesses as to what may be responsible for blood sugar elevations on a low carb diet.

Jenny said...

A high hematocrit might point to hemochromatosis which can cause high blood sugars independent for diet. It's often genetic. Have you been tested?