My HbA1c is normal. Then why is my blood glucose 205 mg/dL?

A 35-year-old school teacher recently walked into my clinic with a question that many people with diabetes, or at risk of diabetes, may find familiar. A few weeks earlier, she had undergone a routine health check-up. Like many health-conscious individuals, she was particularly interested in her HbA1c, an average blood sugar count of three months and a test widely used to diagnose and monitor diabetes. Her HbA1c was 5.6%. The laboratory had marked it as normal. Reassured by the report, she assumed that diabetes was not something she needed to worry about.

Life moved on. But over the next few weeks, she began noticing subtle changes. She felt unusually tired by the end of the day. She was drinking more water than usual and making frequent trips to the bathroom. She occasionally woke up at night to pass urine. Initially, she blamed these symptoms on stress, summer heat, a demanding work schedule, and the challenges of managing both a career and a young family. When the symptoms persisted, she visited her family physician. A random blood glucose test was performed. The result was 205 mg/dL. She stared at the report in disbelief. “How can my blood glucose be high when my HbA1c is normal?” It is a situation that many people encounter.

HbA1c is valuable, but it is not perfect

Most regard HbA1c as the gold standard test for diabetes. In most situations, that belief is justified. HbA1c reflects the amount of glucose attached to haemoglobin, the oxygen-carrying protein inside red blood cells. Since red blood cells survive for roughly three months, the test provides an estimate of average blood glucose exposure during the preceding three months. This makes it an excellent tool for assessing long-term glucose control.

However, there is one important fact that often gets overlooked. HbA1c is an average. And averages can sometimes be misleading. Imagine a city that enjoys pleasant weather for most of a season but experiences an intense heatwave during the final two weeks. The average temperature may still appear normal despite a recent period of extreme heat. Blood glucose behaves in much the same way.

When glucose rises faster than HbA1c

One explanation for the apparent contradiction is that blood glucose levels have increased relatively recently. A person may have had normal glucose values for most of the previous three months and developed significant hyperglycaemia only in the last few weeks. In such a situation, the HbA1c may still appear normal because it continues to reflect the earlier period of normal glucose levels. The blood glucose measurement reflects what is happening now. The HbA1c reflects what has happened over several weeks. The two tests are therefore looking at different time periods.

This phenomenon is not uncommon. Some individuals develop diabetes quite rapidly. Others experience a sudden deterioration in glucose control because of illness, medications, pancreatic disorders, significant weight gain or increasing insulin resistance. In these situations, blood glucose often rises before HbA1c has had sufficient time to catch up.

A lesson we learnt during COVID-19

Doctors around the world encountered this exact scenario during the COVID-19 pandemic. Patients who had never previously been diagnosed with diabetes suddenly presented with blood glucose levels of 200, 300, or even 400 mg/dL. Yet some had HbA1c values that appeared only mildly elevated or even close to normal. Acute infections trigger the release of stress hormones such as cortisol and adrenaline. These hormones increase glucose production by the liver and reduce the effectiveness of insulin. Many patients also received steroids, which can substantially raise blood glucose levels. As a result, glucose levels often increased rapidly over days or weeks. The HbA1c simply did not have enough time to reflect these changes.

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Sometimes the HbA1c itself is misleading

In other situations, the issue is not recent hyperglycaemia. The issue is that HbA1c may not accurately reflect true glucose exposure. HbA1c depends on two assumptions. First, that haemoglobin has a normal structure. Second, that red blood cells survive for a normal length of time. When either of these assumptions is violated, the test can become unreliable. Conditions such as thalassaemia, HbE trait, HbD trait, sickle cell disease, and other haemoglobin variants alter the structure of haemoglobin. Depending on the laboratory method used, these conditions may produce falsely low or falsely high HbA1c values. This is particularly relevant in India, where haemoglobin variants are relatively common and often remain undiagnosed.

HbA1c is also influenced by how long red blood cells remain in circulation. If red blood cells are destroyed prematurely, they have less time to accumulate glucose. The HbA1c may, therefore, appear lower than expected. This can occur in certain forms of anaemia, haemolytic disorders, chronic liver disease, and following significant blood loss. Conversely, some conditions prolong red blood cell survival and can lead to higher HbA1c values. The result is that HbA1c becomes a reflection not only of glucose levels but also of red blood cell biology.

What about pregnancy?

During pregnancy, red blood cell turnover changes, iron deficiency is common, and glucose levels can evolve rapidly as pregnancy progresses. A woman may therefore have a normal HbA1c yet still develop significant glucose intolerance or gestational diabetes. This is one reason why HbA1c is not the primary test used for diagnosing gestational diabetes.

Looking beyond one number

Today, several tools are available for evaluating glucose control. Fasting glucose measurements provide information about baseline glucose regulation. Post-meal glucose testing helps identify abnormalities that may be missed by fasting measurements alone. Continuous glucose monitoring offers a detailed picture of glucose patterns throughout the day and night. HbA1c remains a powerful and valuable test, but it is only one piece of the puzzle. When symptoms and test results do not agree, further evaluation is often necessary.

(Dr Bhattacharya is senior consultant, Endocrinology, Apollo Hospitals, Delhi)