Different monitoring techniques for blood glucose control can give different results

Type 1 diabetes is an immunological disease that destroys the insulin-producing cells of the pancreas. The disease therefore requires continuous treatment with insulin. Keeping blood glucose at a good level reduces the risk of both acute problems and longer-term complications, such as organ damage.

The goal is to keep blood glucose levels in the range of 3.9-10 mmol/l for most of the day. Traditionally, blood glucose levels are checked using the HbA1c (Hemoglobin A1c) blood test, which can be taken with a finger-prick test during a healthcare visit. The HbA1c test measures how much glucose has accumulated on the hemoglobin in the red blood cells and can reveal blood glucose levels over the past two to three months. The sample is therefore often also called long-term glucose.

Sensor under the skin

Currently in Sweden, the vast majority of people with type 1 diabetes have a sensor under the skin that continuously monitors glucose levels (CGM). In the current study, the researchers compared mean glucose measured with this technology, as well as other CGM measurements with HbA1c measured over the same period.

Image

“Some studies have suggested that HbA1c and mean glucose over the same time period do not always appear to be as well matched as previously thought. It is therefore important for both patients and caregivers to understand how these measurements are related in order to optimize diabetes treatment,” says Sofia Sterner Isaksson, who is a PhD student at Sahlgrenska Academy at the University of Gothenburg and a dietitian in the NU healthcare system.

Individual differences

The results of the study are published in the journal Diabetologia. The study involves blood glucose monitoring using both methods in 144 people followed for two and a half years in 15 hospitals and measured using the same methods and the same type of CGM. For 10% of the individuals in the study, there was a noticeable difference. Although the continuous glucose monitoring with CGM showed the same mean glucose, the monitoring with HbA1c differed by 8 mmol/mol or more.

“We see that HbA1c shows strong correlations with mean glucose values and also with percent time in target range measured with CGM. At the same time, we also see that there are major differences between individuals that also persist over time,” says Sofia Sterner Isaksson.

Image

Implications for treatment

These differences have implications for the treatment of patients with type 1 diabetes. For a patient at the target level for most adults (52 mmol/mol), the mean glucose level may actually be much higher, corresponding to an HbA1c of 60 mmol/mol.

“If this is not observed during clinical visits, the patient risks being undertreated and receiving suboptimal treatment with elevated blood glucose levels,” says Sofia Sterner Isaksson.

Similarly, there are risks of overtreatment if patients who have high HbA1c values relative to corresponding low mean glucose levels are not identified.

“In worst case scenarios, it can increase the risk of hypoglycemia, i.e., excessively low blood glucose levels, which is often unpleasant. It affects cognition and, in the worst case, can lead to unconsciousness. Patients may also feel misunderstood if they have a high HbA1c, but a glucose level that is actually good, if they are not given explanations for these correlations,” says Sofia Sterner Isaksson.

Probable genetic cause

The exact cause of the difference between HbA1c and mean glucose is not known, but researchers believe that the root cause is largely genetic. It is likely that there are genetic variations that affect the transport of glucose into the red blood cells, and different biological variations that affect the storage of glucose on the hemoglobin.

Both monitoring methods have advantages and disadvantages. Although CGM is becoming increasingly influential in diabetes care, many people do not have CGM, including most people with type 2 diabetes. HbA1c also remains an important measurement as studies looking at long-term complications are still based on HbA1c.

Deeper understanding with CGM

The researcher responsible for the study is Marcus Lind, Professor of Diabetology at the University of Gothenburg and Senior Physician at Sahlgrenska University Hospital/Östra and within the NU-Hospital Group. He thinks it is an advantage for diabetes care that there are different methods of monitoring blood glucose, but he also understands that it can be challenging to explain the differences between the measurement results to patients.

Image

“With CGM, we can gain a deeper understanding of a patient's blood glucose control. CGMs are becoming increasingly influential, and it would be valuable to have an independent international quality assurance system. Today, the systems have differences that can complicate the interpretation of CGM data in clinical practice,” he says. Good knowledge to interpret both CGM and HbA1c data is important in healthcare and how different measurements relate to each other.

The study is based on the so-called GOLD and SILVER studies. Of the patients included, the vast majority had healthy kidneys and low levels of comorbidity. In addition, the people were predominantly of the same ethnicity, which can also affect the HbA1c level.