How to Measure the level of glycation in the body
1. HbA1c, glycated hemoglobin, hemoglobin A1C test
It is the most popular and widely used test method to determine the level of glycation in the body. It can be obtained as an additional test during regular health check-ups. This test measures the proportion of glycated hemoglobin, which is the hemoglobin that has been bound to glucose. Higher values indicate higher average blood glucose concentrations.
When hemoglobin becomes glycated, it remains in that state until the red blood cells carrying hemoglobin reach the end of their lifespan and are removed from circulation. Typically, red blood cells have a lifespan of about 120 days. During this period, the measurement of glycated hemoglobin (HbA1c) reflects the estimated average blood glucose levels over that time frame. HbA1c measurement reflects the cumulative glycation that has occurred over the lifespan of a given red blood cell. As new red blood cells are continually produced and old ones are removed from circulation, the HbA1c level reflects recent average changes in glycemic control over approximately 2-3 months. It will reflect.
For reference, it is known that an HbA1c value below 5.7% is considered within the normal range, while a value between 5.7% and 6.4% is considered prediabetes. An HbA1c value of 6.5% or higher is indicative of diabetes [1].
Mayo Clinic has provided the percentage of glycated hemoglobin test results and generally corresponding blood sugar levels as shown in the table below. [2]
HbA1c level and corresponding blood sugar level
2. Glycated albumin
In situations where the metabolism of hemoglobin can be affected, such as hemolytic anemia, secondary anemia or iron deficiency anemia, hemoglobinopathies, pregnancy, and uremia, there is a possibility of misinterpreting HbA1c test results [3]. In such cases, glycated albumin can be used as an alternative test because it is not influenced by these conditions. While HbA1c reflects average blood glucose levels over 2-3 months, glycated albumin evaluates blood glucose levels over a shorter duration of 2-4 weeks, potentially providing more reliable data. However, this test can also be unreliable in conditions that affect albumin metabolism, such as chronic hepatitis or liver cirrhosis, as the liver synthesizes albumin.
3. Skin fluorescence measurement technology
Among AGEs, there are those that can emit fluorescence on their own due to certain chemical changes during their creation. Skin fluorescence measurement technology utilizes this property by exposing the skin to light of a specific wavelength that interacts with AGEs and then measuring the fluorescence response. This method quantifies the skin fluorescence of AGEs. The technique involves illuminating the skin with light in the range of 300-400nm, penetrating into the skin to activate AGEs, and then measuring the fluorescence values. Two devices that have been developed for this purpose, AGE Reader (Netherlands) and the SCOUT DS SF Spectrometer (United States). Both devices measure the accumulation of AGEs in the skin, but they differ in their measurement techniques [4].
Some research results using HbA1c levels
1. Relationship between HbA1c level and mortality
There is a study that tracked the relationship between glycated hemoglobin (HbA1c) and mortality in 4,662 adult men aged 45 to 79 years. [5] According to this study, men with diabetes had an increased risk of cardiovascular disease, ischemic disease, and all-cause death compared to men without diabetes. This can be mainly explained by glycated hemoglobin, and people with a glycated hemoglobin concentration of less than 5% had the lowest mortality rate. The finding that for a 1% increase in HbA1c concentration the risk of death increased by 28%, independent of age, blood pressure, serum cholesterol, body mass index, and smoking habits, is quite surprising. As a result, this study highlights that efforts to lower HbA1c levels through lifestyle changes may help reduce the risk of death in the general population.
Additionally, a meta-analysis study based on 46 published papers found that both individuals with diabetes and those without diabetes had an increased risk of all-cause mortality when HbA1c levels exceeded 8.0% and 6.0%, respectively.[6] HbA1c is considered to be the most relevant risk factor for all-cause mortality and cardiovascular mortality in both diabetic and non-diabetic individuals. The study determined the optimal HbA1c levels for reducing mortality rates to be between 6.0% and 8.0% for individuals with diabetes and between 5.0% and 6.0% for individuals without diabetes.
2. Relationship between HbA1c level and Alzheimer’s disease
According to a study analyzing the relationship between HbA1c levels and dementia in 1,342 elderly individuals, including Alzheimer's disease dementia, it was found that the risk of developing dementia increased by 2.8 times when the HbA1c level was below 6.5%. [7] Furthermore, dementia was found to increase by 5 times and Alzheimer's disease dementia by 4.7 times when the HbA1c level was 7% or higher. These results indicate that the risk of various types of dementia in the elderly population increases as HbA1c levels rise.
Another study conducted a meta-analysis using five studies that included a total of 577,592 diabetes patients (99% type 2 diabetes patients) and had an average follow-up period of over 6 years [8]. This study also concluded that higher variability of HbA1c is associated with a higher incidence of dementia in patients with diabetes. During this period, 31,963 patients were newly diagnosed with dementia.
3. Relationship between HbA1c and renal failure
A study evaluated the association between HbA1c and chronic renal failure and cardiovascular disease in a random sample of 2,270 adults in southern Spain. Patients with diabetes are twice as likely to develop chronic renal failure or cardiovascular disease, and a 1% increase in HbA1c levels increases the incidence of both by 30% to 40%, regardless of whether the patient has diabetes. [9]
4. Relationship between HbA1c and skin
Accumulation of AGEs can have negative effects, especially in long-lived proteins and peptides, and is associated with oxidative stress and inflammation caused by AGEs interacting with receptors on the cell surface, altering the structure and function of proteins.
Long-lived proteins refer to those that persist in the body for a longer duration or have a longer half-life compared to other proteins. These proteins play a structural and functional role in maintaining the integrity of cells and performing essential functions over an extended period. Collagen, for example, provides strength and structure to tissues such as the skin, tendons, and bones, and can last for years. Similarly, enzymes involved in metabolic processes and structural proteins such as keratin in hair and nails can persist for months or years.
When AGEs accumulate in these proteins, their structure and function change, which can lead to AGEs-related pathologies. Long-lived proteins, such as the skin matrix, are also highly susceptible to these modifications, which can make skin tissue stiffer, reduce elasticity, and increase reactive oxygen species (ROS) caused by ultraviolet rays (UVR). [10]
Furthermore, many studies have shown that chronic exposure to ultraviolet rays promotes the formation of AGEs. However, it's worth noting that the impact of AGEs on the skin differs between the dermis and the epidermis. Unlike the dermis, which contains long-lived proteins that are vulnerable to deformation, the protein circulation in the epidermis is much faster and is continuously regenerated, so the modified proteins are lost as cells are replaced.
Let’s look at research reports related to skin aging. One of the mechanisms implicated in aging is the glycation process, and the emergence of AGEs has been identified as one of the causes of skin aging. Although AGEs accumulate during the natural aging process and in healthy skin, many studies have shown that the accumulation of AGEs is much more severe in skin exposed to ultraviolet rays. [11]
We have explored methods to measure the accumulation of AGEs in our bodies, and researches utilizing HbA1c as an easily accessible measure of average glycation levels have been examined to estimate the relationship between glycation and major diseases.
[References]
[1] Hemoglobin A1Chttps://www.ncbi.nlm.nih.gov/books/NBK549816/
[2] Mayo Clinic A1C test
https://www.mayoclinic.org/tests-procedures/a1c-test/about/pac-20384643
[3] Glycated albumin: a potential biomarker in diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118799/
[4] Skin fluorescence as a clinical tool for non-invasive assessment of advanced glycation and long-term complications of diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975757/
[5] Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk)
[6] Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis
[7] Elevated HbA1c is associated with increased risk of incident dementia in primary care patients
[8] HbA1c Variability and the Risk of Dementia in Patients with Diabetes: A Meta-Analysis
https://pubmed.ncbi.nlm.nih.gov/35685543/
[9] Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population
https://bmcnephrol.biomedcentral.com/articles/10.1186/1471-2369-14-151
[10] Advanced glycation end products in skin ageing and photoageing: what are the implications for epidermal function?
[11] Expression of Advanced Glycation End-Products on SunExposed and Non-Exposed Cutaneous Sites during the Ageing Process in Humans
