Strengths and shortcomings of HbA1c
The HbA1c has strengths and shortcomings. One strength is that it's more informative than a fasting blood glucose. Fasting glucose can be elevated for a number of reasons even on a low-carb or keto diet, such a bad night's sleep, and as noted, it's only a one-time snapshot. HbA1c is a better approximation of your blood glucose levels over the course of many weeks.
A major shortcoming, however, is that the HbA1c provides no information about insulin levels. It's possible - common in fact - to have a normal HbA1c but very high insulin. Elevated insulin levels mean your pancreas is working hard to keep your blood glucose at normal levels. Chronically high insulin is a major driver of metabolic disease even when fasting glucose and HbA1c are normal.
Another shortcoming of HbA1c is that it's based on the assumption that red blood cells (RBCs) live approximately 120 days. However, for reasons we'll explore shortly, this is not always the case. HBA1c therefore may not be a completely accurate reflection of average blood glucose in people whose RBCs have a shorter or longer lifespan.
However, while the absolute number may be open to interpretation, the trend in the results of your HbA1c can be very helpful. For instance, if your red blood cells have a longer half life, your absolute A1c will tend to be higher. However, if that number goes down over time as you lose weight or embark on other lifestyle changes, then that trend information is very useful feedback that your blood sugar control is improving. And if your HbA1c is trending up, that means you need to pay attention to bringing your blood sugar back under control.
Reasons why your HbA1c might be higher or lower than expected
In some cases, the HbA1c may not be a completely accurate proxy for estimated average blood glucose. In fact, some people with very poor blood glucose control may have a lower-than-expected HbA1c, while those with excellent blood glucose control may have an HbA1c that's slightly higher than expected. That may be because of any of these factors:
- Shorter RBC lifespan: Chronically elevated blood glucose is damaging to RBCs, so their lifespan may be shorter than 120 days in someone with poorly-controlled type 2 diabetes. A shorter lifespan means these cells have less time for blood sugar to stick to them (to become glycated). In such a situation, it's unlikely that someone would have an HbA1c in the non-diabetic range, but it might be lower than would be expected, leading individuals and their physicians to believe their diabetes is better controlled than it actually is. Studies show the higher the HbA1c, the shorter the RBC lifespan - as short as 81 days - and the greater the underestimation of the actual blood glucose level.
- Longer RBC lifespan: While no research has yet confirmed this assumption, many low carb researchers hypothesis that healthy people - or people who have recently adopted a low carb diet - may have longer RBC lifespans. At this stage, however, this is conjecture. However one study did show that in people who don't have diabetes, RBCs can live as long as 145 days - nearly three weeks longer than the typically cited 120-day average. This longer life span could give the cells more time to become glycated, which could result in an artificially high HbA1c. In these individuals fasting glucose would likely be normal and glucose after meals be normal as well. People in this scenario would likely not have an HbA1c in the diabetic or pre-diabetic range, but it might be higher than they would otherwise expect - for example, 5.4% rather than 5.0%.
- Anemia: Another factor affecting RBC lifespan and, therefore HbA1c, is anemia. Some types of anemia result in a shortened lifespan for RBCs, contributing to an artificially low HbA1c. However, iron deficiency anemia may be associated with higher HbA1c in both people with diabetes and without.In fact untreated iron deficiency anemia can misclassify people as having diabetes. One study's authors note: "Iron deficiency must be corrected before any diagnostic or therapeutic decision is made based on HbA1c."
- Genetic factors: Ethnic and genetic factors influence RBC lifespan and HbA1c. People of African, Mediterranean, or Southeast Asian descent may have hemoglobin variants that influence the accuracy of HbA1c. Other variants are found in individuals from other parts of the world. Some laboratories take hemoglobin variants into account in their tests, but others don't. These variants include genes for sickle cell anemia and beta thalassemia. Dr. Peter Attia has written about his personal experience with this. Of Mediterranean ancestry, he carries a gene for beta thalassemia, a type of anemia that affects hemoglobin production and RBC size. His continuous glucose monitor showed that he had excellent average blood glucose control (92 mg/dl (5.1 mmol/L), which would correlate to an HbA1c of 4.6 to 4.9 %. However, his HbA1c lab tests were typically 5.5 to 6.0% - not just substantially higher, but in the pre-diabetes range.
Other ways to assess glycemic control beyond HbA1c
HbA1c can be helpful when assessing metabolic health, but is best when used as part of a larger picture. Here's a quick look at some additional ways to evaluate your blood sugar control and metabolic health:
- Fasting insulin test or HOMA-IR: As mentioned earlier, many people have high insulin levels even when their HbA1c and fasting glucose are normal. A fasting insulin test can tell you whether your fasting insulin level is high, and combining fasting insulin with fasting glucose gives your homeostatic model assessment of insulin resistance (HOMA-IR). This test tells you how hard your pancreas is working by pumping out insulin to keep your blood glucose in the normal range. The HOMA-IR may be a more informative measurement than either fasting insulin or glucose by themselves because it helps you see the relationship between insulin levels and blood glucose levels, and tells you how insulin sensitive or insulin resistant you are.
- Fructosamine: Similar to HbA1c, fructosamine levels indicates your glycemic control but during the previous two to three weeks rather than months. Fructosamine is a compound formed when glucose sticks to other proteins in the blood that only exist for 14 to 21 days. The percentage of glycated proteins in the fructosamine test reflect average glucose levels during this shorter timeframe. It is not believed to be affected by red blood cell lifespan. In addition to being an indicator of glycemic control, fructosamine can be useful for gauging the recent impact of changes in diet, medication, and lifestyle. (However, fructosamine is not a routine test and may not be available everywhere.)
- Glycated albumin: One of the most abundant proteins in blood, albumin also has sugar in the blood stick to it over time. Its percentage of glycation reflects mean glucose levels over the prior two to three weeks. This test is relatively new and is not widely available.
- Continuous glucose monitor (CGM): Measuring blood glucose in real-time with a CGM provides very accurate data about your blood sugar levels. If you've been surprised by an HbA1c that's higher than you expected, a CGM will show you more reliably what your blood glucose is doing after meals and throughout the day. A CGM is available with a prescription from your doctor, but insurance companies usually only pay for it for people with type 1 diabetes. Others will need to pay out of pocket.
- HbA1C plus an oral glucose tolerance test (OGTT): Drinking a 75g glucose solution and measuring your immediate blood sugar response, called an OGTT, can assess your blood sugar control when combined with the results of your HbA1C. In fact, a recent study found that, based solely on HbA1c, 73 % of subjects appeared to have normal blood glucose levels, but the OGTT showed that their blood glucose rose into the diabetic range. Do note, if you've been following a low-carb or ketogenic diet, the OGTT may give a false result. Most keto-friendly physicians recommend that you "carb up" by consuming 100-150 grams of carbs daily for about a week prior to taking the test in order to prepare your body to once again burn carbs - otherwise it may falsely indicate that you have diabetes.
- Triglyceride to HDL ratio: A fasting blood test that looks at the relationship between your triglycerides and your high-density lipoprotein (HDL) provides information about your metabolic health without measuring blood glucose at all. In general you want your triglycerides to be low and your HDL to be high. To get the ratio divide your triglyceride number by your HDL number. The closer the ratio is to 1 the better, with the cut off for a "low" ratio being 1.7 - as long as the HDL is above 40 mg/dL. The higher the triglycerides and the lower the HDL, the higher the ratio, with a hazardous ratio being anything above 3.0.A high TG-HDL ratio is part of the diagnostic criteria for metabolic syndrome and insulin resistance and predicts increased risk for type 2 diabetes as well as cardiovascular disease and heart attacks.
- Waist to height ratio or waist to hip ratio: The size of your waist in relation to your height, or in relation to your hips, are both indicators of metabolic health and insulin sensitivity. Greater abdominal circumference is related to a greater risk of diabetes, hypertension, cardiovascular disease and overall mortality even in people of normal weight. To get your ratios just divide your waist measurement by either your height or hip measurement to get a number. Or you can use an online calculator. A waist to height ratio less than 0.5 indicates good insulin sensitivity, while a higher number indicates insulin resistance. Likewise, a waist to hip ratio of less than .9 for men and .85 for women is healthy.
Summary
HbA1c is a very important measurement of your metabolic health that should ideally be taken regularly - perhaps once a year - by your doctor. If you have received a diabetes diagnosis it should be taken more often, perhaps once every three months.
The trend of your HbA1c results over time gives you a good indication about your blood sugar control. If you start eating a low-carb, ketogenic diet, you should see that HbA1c result trend down, often quite dramatically. If HbA1c starts increasing, more carbohydrates may be creeping into your diet or other factors, such as stress or sleep, may be impacting your blood sugar control.
Like any other health marker, however, a single HbA1c result does not give a complete picture of your health. It helps to work with a qualified medical professional to understand the total picture of your health, using different clinical measurements as well as your own assessment of how you feel.
