The hemoglobin A1C test is usually done to diagnose type II diabetes and monitor type I and II diabetics for proper blood sugar control, but HbA1C values indicate much more than glycemic control. Even non-diabetics can benefit from paying attention to their HbA1C values.
The HbA1C test and how it works:
Hemoglobin is a crucial protein within red blood cells that binds oxygen and carries the vital molecule around the body. There are different types of Hemoglobin, but hemoglobin A (HbA) makes up over 90%.
Red blood cells are simple cells, kind of like bags of hemoglobin, and they freely take up glucose without the help of insulin. Sugars like glucose have reactive portions that form linkages with the amino groups of amino acids, the constituents of proteins.
When a sugar reacts with and binds to a protein without the catalytic help of an enzyme it’s called glycation or non-enzymatic glycosylation. The glycated form of HbA is denoted HbA1C. By conventional standards if the percentage of glycated hemoglobin makes up more than 5.6% of total HbA that’s indicative of abnormal glucose metabolism.
Generally a direct relationship exists between average blood glucose levels and A1C values. The higher blood sugar levels get after meals and stay elevated, i.e. the less efficiently glucose is metabolized by the body, the more glycation occurs. For example, an A1C of 5% indicates an average blood sugar of about 90 mg/dL for the last few months; an A1C of 6% indicates an average blood sugar of 135 mg/dL.
The strength of the test is in the lifetime of the red blood cell – about 120 days. The percentage of glycated hemoglobin gives an estimate of average blood sugar level for the last three to four months. Other blood sugar tests like fasting glucose only give snapshots of what blood sugar levels look like at a given moment in time. Another strength is that the test can be drawn at any time, there’s no fasting required, and it’s inexpensive.
The glycation of proteins throughout the body is a frequent occurrence that is not specific to hemoglobin.
The A1C test is a great barometer of systemic glycation of proteins because hemoglobin is a protein like any other in the body. The more glucose there is floating around the bloodstream, the more opportunity it has to link itself to hemoglobin and proteins in all tissues.
The binding of glucose to proteins may sound harmless, and though it’s a natural process, glycation can be destructive. Proteins maintain the body’s structural integrity and perform various physiological functions, but when proteins are glycated they suffer structural changes that often translate to functional changes.
High levels of glycation play a role in the development of cardiovascular disease, neurodegenerative diseases, accelerated aging of the body inside and out, and in many of the complications seen in diabetes: damage to the nerves and blood vessels resulting in blindness, kidney failure, poor wound healing, amputations, and the progression of cardiovascular disease leading to strokes, heart attacks, and heart failure.
Glycation of proteins at first forms unstable structures that over time settle to become what are known as advanced glycation end products (AGEs).
AGEs are a major instigator in the process of inflammation throughout the body. They are in a large part responsible for irritating the cells (endothelium) lining arteries and have been detected in lesions of the coronary arteries of diabetic patients. They also cause the production of reactive oxygen species, known as free radicals, that go on to cause more damage.
AGEs are in large part responsible for neurodegenerative diseases like dementia.They damage vessels of all sizes around the body, including vessels of the brain, compromising the delivery of oxygen and nutrition to neurons. In the progression of Alzheimer’s AGEs build up in the brain leading to amyloidosis causing neuronal destruction and brain shrinkage.
An above normal level of glycation in the body exceeds the rate of brain shrinkage caused by carrying the Alzheimer’s gene. In other words, the effects of having the gene and having high blood sugar levels are additive. If one carries the Alzheimer’s gene the best thing to do is strictly control blood sugar levels to limit the production of AGEs.
Diabetics are two times more likely to develop Alzheimer’s disease. Many studies have shown that diabetics have a higher concentration of plasma AGEs because they suffer from higher average blood sugar levels, but in a longitudinal study published in the New England Journal of Medicine, researchers took things a step further. For about seven years they tracked blood sugar levels and glycated hemoglobin of 2,067 subjects to understand the link between blood sugar levels and dementia. None of the participants had dementia, but some had diabetes at the beginning of the study.
524 of the 2,067 subjects — about 25% — developed dementia by the end of the study. That included 450 out of 1,724 subjects who did not have diabetes by the end of the study. In short, they found that there was no threshold where risk went up or down. Incremental increases in blood sugar concentrations were associated with increased risk of dementia.
AGEs also cause accelerated aging, and not just increased wrinkle formation the skin. AGEs damage collagen, one of the most abundant proteins in the body. Among its many roles in the body, collagen gives tissues of internal organs and the skin structural support, protection, and resilience. AGEs cause the cross linking of collagen, destroying its form and ability to properly maintain the structural integrity of the body. This is especially bad for blood vessels that harden as a result of the cross linkage.
AGEs don’t only go around damaging cells and proteins. They can get inside cells and alter enzymes, proteins, DNA, and signaling pathways that direct day to day cellular activities. Changes in cellular machinery can mean serious cellular malfunction and in the worst cases of cellular derangement — cancer.
Limitations of the HbA1C test:
The accuracy of the A1C test has been improved by the National Glycohemoglobin Standardization Program (NGSP). However, when it is used for diagnosis of diabetes, the blood sample must be sent to a laboratory that uses an NGSP certified analysis to ensure standard results.
Sometimes blood samples analyzed in a healthcare provider’s office are not standardized for diagnosing diabetes. The test results can vary by 0.5% on either side of the actual percentage. This means that an A1C measured as 8.0% could indicate a true A1C anywhere in the range from 7.5 to 8.5%. Still it is useful to do in the doctor’s office to get an idea of where one’s glycemic health stands and to make any dietary modifications if necessary from there.
False A1C results may also occur in people for several reasons. For example, a falsely low A1C result can occur in people with anemia and heavy bleeding, and in patients whose RBC lifespan is shorter than normal. Family members of those with Sickle Cell Disease and other hemoglobin disorders may have a less common type of hemoglobin can interfere with the test.
Also, the actual amount of AGEs formed in the body might be even higher than indicated by the A1C test. Fructose from sources like high fructose corn syrup, a substance the American diet is littered with, is even more reactive than glucose and also forms AGEs. Insulin resistance, the condition underlying type II diabetes, causes impaired lipid and glucose metabolism resulting in the excess production of sugar derivatives called aldehydes that react with proteins and amino acids to form AGEs as well.
The American Diabetes Association recommends keeping glycated hemoglobin under 7% for diabetics and under 5.7% for people who do not have diabetes but emerging research suggests that for optimal health, we should strive for 5% and lower in order to counteract the onset of diabetes, dementia, heart disease, and other chronic conditions.
Moran, Chris et al. 2015. Type 2 Diabetes, Skin Autofluorescence, and Brain Atrophy. Diabetes: 64(1):279-283.
Münch G. et al. 2010. Advanced glycation endproducts and their pathogenic roles in neurological disorders. Amino Acids: 42(4):1221-36.
Vasdev S. et al. 2007. Role of Advanced Glycation End Products in Hypertension and Atherosclerosis: Therapeutic Implications. Cell Biochem Biophys: 49, 48–63.