Why Hemoglobin A1c Is Not a Reliable Marker | Chris Kresser
HCTP Banner

Why Hemoglobin A1c Is Not a Reliable Marker

by

Last updated on

iStock.com/104240029

Over the last few years doctors are increasingly relying on a test called hemoglobin A1c to screen for insulin resistance and diabetes. It’s more practical (and significantly cheaper) than post-meal glucose testing, and it’s less likely to be skewed by day-to-day changes than fasting blood glucose.

What is hemoglobin A1c?

Sugar has a tendency to stick to stuff. Anyone that has cooked with sugar can tell you that. In our bodies, sugar also sticks – especially to proteins.

The theory behind the A1c test is that our red blood cells live an average of three months, so if we measure the amount of sugar stuck to these cells (which is what the hemoglobin A1c test does), it will give us an idea of how much sugar has been in the blood over the previous three months.

The number reported in the A1c test result (i.e. 5.2) indicates the percentage of hemoglobin that has become glycated (stuck to sugar).

Why is hemoglobin A1c unreliable?

While this sounds good in theory, the reality is not so black and white. The main problem is that there is actually a wide variation in how long red blood cells survive in different people. This study, for example, shows that red blood cells live longer than average at normal blood sugars. Researchers found that the lifetime of hemoglobin cells of diabetics turned over in as few as 81 days, while they lived as long as 146 days in non-diabetics.

This proves that the assumption that everyone’s red blood cells live for three months is false, and that hemoglobin A1c can’t be relied upon as a blood sugar marker. In a person with normal blood sugar, hemoglobin will be around for a lot longer, which means it will accumulate more sugar. This will drive up the A1c test result – but it doesn’t mean that person had too much sugar in their blood. It just means their hemoglobin lived longer and thus accumulated more sugar. The result is that people with normal blood sugar often test with unexpectedly high A1c levels.

This confused me early in my practice. I was testing blood sugar in three different ways for all new patients: fasting blood glucose, post-meal blood sugar (with a glucometer) and A1c. And I was surprised to see people with completely normal fasting and post-meal blood sugars, and A1c levels of >5.4%.

In fact this is not abnormal, when we understand that people with normal blood sugar often have longer-lived red blood cells – which gives those cells time to accumulate more sugar.

On the other hand, if someone is diabetic, their red blood cells live shorter lives than non-diabetics. This means diabetics and those with high blood sugar will test with falsely low A1c levels. And we already know that fasting blood glucose is the least sensitive marker for predicting future diabetes and heart disease. This is a serious problem, because fasting blood glucose and hemoglobin A1c are almost always the only tests doctors run to screen for diabetes and blood sugar issues.

Another condition that affects hemoglobin A1c levels is anemia. People who are anemic have short-lived red blood cells, so like diabetics, they will test with falsely low A1c levels. In my practice, about 30-40% of my patients have some degree of anemia, so this is not an uncommon problem.

What blood sugar markers are reliable?

Testing accurately for blood sugar is like putting pieces of a puzzle together. Fasting blood glucose, A1c and post-meal blood sugar are all pieces of the puzzle. But post-meal blood glucose testing is by far the most reliable and accurate way to determine what’s happening with blood sugar, and the most sensitive way of predicting future diabetic complications and heart disease.

For more on why post-meal blood sugar is a superior marker, read my article When Your Normal Blood Sugar Isn’t Normal (Part 2). To learn how to test your post-meal blood sugars at home, and what healthy targets should be, read my article How to Prevent Diabetes and Heart Disease for $16.

Another useful – but underused – blood sugar marker is fructosamine. Fructosamine is a compound that results from a reaction between fructose and ammonia or an amine. Like A1c, it’s a measure of average blood sugar concentrations. But instead of measuring the previous 12 weeks like A1c, fructosamine measures the previous 2-3 weeks. And unlike A1c, fructosamine is not affected by the varying length of red blood cell lifespans in different individuals. Fructosamine is especially useful in people who are anemic, or during pregnancy, when hormonal changes cause greater short-term fluctuations in blood glucose levels.

To put the most accurate picture together, I like to have all four: fasting blood glucose, A1c, post-meal glucose and fructosamine. But if I only had to choose one, it would definitely be post-meal glucose.

256 Comments

Join the conversation

  1. Hi Chris,

    I’ve heard conflicting results about the effects of iron-deficiency anemia on A1c levels. I had an elevated A1c of 5.8, and my GP said that anemia falsely lowers A1c, while an endocrinologist said it can falsely raise it. My ferritin level at the time were very low (4, since increased to 14). I’m a runner with a low BMI and low blood pressure and no other indications of metabolic disorder. Can iron-deficiency cause a falsely high A1c?

    I’ve also struggled with amenorrhea for over a year (PCOS has been ruled out). Can anemia can affect menstruation? Again, I’ve gotten conflicting responses from my doctors.

    Thanks!

  2. Just got my first lab test back (life insurance required it). Since starting low-carb, high-protein 9 months ago, and regular CrossFitting, I figured I’d have stellar results.

    Glucose: 80
    Fructosamine: 1.73 (HIGH)
    Hemoglobin A1C: 4.8

    Because I was told not to eat/drink for 6hrs, I don’t have a post-meal glucose level. Anyway, the fructosamine level is freaking me out. I’m 5’9″, 155lbs, with very little body fat. Should I be concerned? I bet my life insurance company is doing to ding me.

    • hmph. I saw “June 22” and i thought the post was from YESTERDAY.. not yesterday three years ago LOL. oops.

  3. Thanks for this information. My A1c generally varies between 6.3 to 7.3 and my fasting sugar remains around 75 to 90 but my PPsugar, two hrs after meal is always between 250 to 270. It never goes down to 200 level. I am on insulin and any higher dose leads to hypoglycemia. Interestingly the ppsugar drops very fast after 3hrs. Is it a delayed action? So how ppsugar can be taken as an yardstick?

    • it nosedives because your insulin has kicked in. MOST peoples blood sugar starts dropping around the 2 hour mark, it takes us longer because we have to wait for the second wave of the insulin to clean up what the first wave left behind. What kind of insulin are you on? Lantis type? Humalin? Humalog? one of the ultra fast acting ones? (im not on that one so i cant remember the names, starts with an A i think lol. ) minute adjustments can usually be made to Regular or fast acting insulin types to avoid blood sugar that is that high, and a low carb diet helps tremendously. My sugar used to be like yours, type 1 insulin dependant diabetic, i figured there was nothing i could do… then i went low carb. Seriously, it is a big change, but blood sugars above 140 are what cause major organ damage and lead to ALL the bad stuff diabetes is known for, and it killed BOTH my parents, who were basically middle aged, certainly not elderly. (dad was 56, mom was 61 when they died…) Dont be like them. The bread, sugar, and pasta are soooo not worth it, neither is the fruit. And there is sugar free chocolate that tastes pretty good these days LOL.

  4. I love how your posts bring enough science to the forefront so that practitioners (like myself) can make us of it but so that the everyday person can read it and make some sense of it as well. This is a very thorough overview of a marker a lot of us are watching with our clients, so thanks!

  5. Thank you for the clear explanation. My fasting blood sugar has always been quite low. I participated in a “Community Health Fair Screening” and they sent me a letter telling me I had an A1C of 5.7 and was pre-diabetic. I was a little freaked out! Then they sent a letter saying there had been irregularities that day, and everyone needed to be re-tested. I was reluctant to go to them again, given that I was just a little annoyed. I went to my doctor who again checked my fasting blood sugar. It is low, as usual. She said she would not recommend A1C unless fasting blood sugar was elevated. She also said that getting that test done would indicate that I was suspected diabetic, and that would not be good to have on my medical records. I was still a bit concerned, but your explanation has made me less concerned. I can see how both the numbers could be accurate, and not in conflict. Thank you.

  6. Thanks so much! That explains why my A1c is always around 5.6 when checked every 6 months but my glucose readings were great on the nasty 3 hour glucose tolerance test, despite eating lowish carb until a few days before the test and definitely not accustomed to such a large bolus of sugar.

  7. THANK YOU! I’ve been trying to figure out why my A1C was higher than it should be (close to 6) after a three months of very strict paleo. Now – 9 months into paleo – I rely on a glucometer. Those numbers are great. Fasted is usually in the mid 80s. Virtually every meal I consume keeps me under 110. I’m pretty confident saying that my BG has not been above 120 in the past 6 months and is actually rarely even over 100.

    One weird thing though: My waking BG is one of my higher readings of the day – mid to upper 90s. I actually rises during the night. Sleep is solid, chow is great, exercise is good. Not complaining too much. 9 months in and I’m down 60-70 lbs, BP is down about 30 pts sys and dys, and bloodwork is great. I have plateaued pretty hard the last 2 months. Gotta figure that one out.

    Thanks again! This explanation of A1C is super helpful!

  8. @Barbara and Susan.

    All health measurements are contextual. If you are eating a diet that has some carbs in it, and your A1c and fasting BG are both high – they are concordant and telling you the same thing – you have poor glucoregulatory control. No need to confirm with fructosamine when fasting BG is high also – over 100 is high.

    Eat VLC with enough low GI carbs to stay out of ketosis – split between lunch and dinner.

    Magnesium 400 mg/ day as citrate (cheaper) or malate.

    Resistance exercise 1-2 x per week.

    Try that, and if numbers don’t come down in a few months, talk to your doctor about metformin

    • Wait, why keep OUT of ketosis? You know, of course that benign dietary ketosis and ketoACIDosis are very different things and have nothing to do with one another except the word “keto” lol. There is nothing wrong with a diabetic being in ketosis, i strive for that, and it is always accompanied by LOW blood sugar, while ketoACIDosis, is always accompanied by very HIGH blood sugar and is very very bad heh.

  9. I’ve been warning about this for some time, but not had time to post on it. This is another example of using a statistic that is useful for populations for individual evaluation – and it can be very inaccurate for the individual. One reason that I stress avoiding lots of measurements.

    I think it’s possible that with reduced oxidative stress red cells could live even longer than normal, as I see perfectly healthy people on PaNU/ Paleo 2.0 diets all the time that have this pattern – low pp BG, no history of DM, good body comp, etc. They have an A1c of around 5.8 or so, then they read Jenny Ruhl or Bernstein and think they are going to die. In my experience, the diabetics or those with history of metsyn seem to achieve lower A1cs than the formerly healthy. There is just no logical reason to think a type I diabetic on Bernstein’s diet is with A1c of 4.8 is actually healthier than a non- diabetic would be on it with A1c of 5.6. I favor red cell survival as accounting for the difference, but it may have to do with de-glycosylation enzyme activity as well – we have such enzymes trying to undo the damage and their activity may depend on how much oxidative damage is going on – pure speculation on that.

    As far as recommendations, I recommend getting A1c and if it is below 5.5 you are done. If it is 5.5 to say, low 6s, do 24 hr and pp bg with fingersticks. If it is much above 6, then confirm it is high with fructosamine.

    PS – for reference, my A1C is 5.6, Stephan Guyenet’s is 5.8. Peter’s is 4.8. Peter is the only one who was ever overweight or had signs of metabolic syndrome among the three of us. Purely anecdotal but interesting. I did a 24 hr BG when I ate VLC and when my A1c was 5.6. The actual BG values correlated with an A1c that should have been about 5.0.

    @Robb

    I was planning to discuss this on your podcast, but it hasn’t happened yet 😉

    • Thank you, thank you. I know this is old, but I must say I have learned a lot from both CK and Kurt Harris. Thank you for this comment. That is me, 5.8; and now I can stop thinking about it.

  10. i have similar numbers to barbara above, and also wonder how worried to be. i am about 35 lbs overweight so i know that’s part of it but i remember being surprised when i attended a pre-diabetes class at kaiser that at least half of the folks there were normal weight or even quite thin. my fasting BG has ranged in the upper 90’s to low 100’s for several years now.

    • Yes Susan! You have to start taking care of yourself! You should visit doctor and see if he suggests you some medication! I had sugar of 126 but HbA1c of 5.7, but still my doctor suggested me medications, exercise and controlled diet… by Exercise I mean brisk walk is also fine but on regular basis. Also I followed 5 things he had to tell me to pay attention to… No Potato, No Sugar, No Fine Wheat Flour.. thats Cake and white bread and stuff.. brown bread is alright in small amounts.. say 4 slices in breakfast is alright.. Drink Lot of Water… and Exercise regularly… and I was able to reduce 20 Kilos in 6 months…. and I am in a healthy range now… things are fine.. and I am off medication… I had to take 6 tablets a day before… Hope this helps.

  11. Last week my doctor told me I had an A1C level of 6.8 and my doctor told me to lose 20 lbs. My glucose level was 105. Do you agree with my doctor

    • Yes Barbara! You have to start taking care of yourself! You should visit doctor and see if he suggests you some medication! I had sugar of 126 but HbA1c of 5.7, but still my doctor suggested me medications, exercise and controlled diet… by Exercise I mean brisk walk is also fine but on regular basis. Also I followed 5 things he had to tell me to pay attention to… No Potato, No Sugar, No Fine Wheat Flour.. thats Cake and white bread and stuff.. brown bread is alright in small amounts.. say 4 slices in breakfast is alright.. Drink Lot of Water… and Exercise regularly… and I was able to reduce 20 Kilos in 6 months…. and I am in a healthy range now… things are fine.. and I am off medication… I had to take 6 tablets a day… Hope this helps.

      • Amit,
        Let your Dr. eat 4 slices of toast for breakfast.
        For the rest of us, I would not go over 1 or 2.

        Think gluten as well as blood sugar

        • Yeah, im going FOUR SLICES??? hehehe. Especially at breakfast! Btw, white vs wheat, if we are talking grocery store bread…=no difference, and with diabetics, its all poison, hehe. Thats ok though, after a while you realize bread has no flavor, especially sandwich bread, so who needs it? Just put the butter RIGHT on the eggs, much better lol. And i got my blood sugar down over 300 points. Yes, that is two zeros.. 300 points lower than it was. Yay low carb high fat diet!!

  12. Glad it was helpful, Robb. A1c was my nemesis for quite a while. Couldn’t explain strange blood sugar patterns I was seeing.

    Alex: CRP is a good measure of systemic inflammation, and has some correlation with CHD, but lowering CRP doesn’t necessarily lower CHD risk. So there’s some murky water there.

  13. last time my A1c was 5.2% – which is 4.8nmol according to my lab report – which is 86mg – which is pretty much my usual fasting level. so why would all the labs and docs still use A1c if it really was THAT unreliable (especially in pre-diabetics)? what would keep them from switching to fructosamines a long time ago, or at least routinely measure both (they’re both rather cheap)? i mean, 3 weeks of average sugar is still plenty to get an overview, or not?

  14. Hi Kris,

    Great article, I think this really clears up what has been going on with me.

    You might recall a couple months back- I was asking about why my A1c was 5.7 when I am full ancestral/paleo nutrition for over a year, lowish carb, 10% body fat, and a competitive athlete. HDL was over 100, triglycerides about 40, CRP less than .1 . My blood sugar levels never went over 120 even after meals and were usually around 86 fasting, but because of the 5.7 A1c my doctor said that I was close to prediabetic levels!

    It freaked me out to be honest, so I did a bunch of research and decided that I must just have long-lived RBCs. It’s good to hear that this is a fairly common occurrence, and this makes a lot more sense.

    Now I’m going to go listen to the Robb Wolf Podcast, I’m excited to hear it.

    Tyler

    • Thank you. Similar readings, Paleo and exercise a bit…but not too much. Employer is making me attend a per diabetic meeting but reading this makes me feel a whole lot better. Will test glucose after a meal now.

    • There must be something about a paleo diet that can have this effect (longer living blood cells). I’ve been on one for four months and tested a little high for blood sugar for the first time every (and I’m extremely healthy – test well on all other health measures). So this article is very helpful! I’ll stop stressing about it 🙂

      • Timely for me to read this. In the same paleo, low carb lifestyle as those in this thread, with my test results of 74 fasting, but 5.7 A1C, just received today. I never hit much above 100 even post-meal due to my lack of carbs ingested. Now I can understand why, and have some peace of mind!

    • Thanks for this, very timely for me!

      I just had my blood tested, fasting blood glucose came back at high normal (89) and A1C just outside of the normal range (5.7) on the high side. I got the standard advice to eat healthier and exercise more. I am a 30 year old male, guessing 15% body fat. Healthy.

      These results puzzled me. I can certainly be stricter about my diet, but I’ve been paleo-ish for 5 years, but I basically consume no sugar except a fruit a day or so and no processed food at all. I exercise an hour a day (BJJ) + walk 10k+ steps daily on average. Hard to improve on without neglecting other parts of my life (work, family).

      I’m not going to freak about this, but are there other factors I could change that could move this?

      My main vice I would say is overeating, especially at night (I usually work evenings and need something after a 4-midnight shift). All literature on overeating seems geared towards overweight people though. There’s also a fair amount of alcohol consumed, although I rarely “get drunk”.

      • did you get an answer for this? I am also in the same boat. Young, healthy, not over weight. Just curious if I should be super strict because I have bad genes, or if it is a fluky test.