HbA1c Unreliability in India and Pakistan: What Patients and Clinicians Should Know

Introduction

HbA1c is widely used to diagnose and monitor diabetes. It reflects the average blood glucose level over the previous two to three months. Many guidelines recommend it because it does not require fasting and is convenient for patients. In India and Pakistan, HbA1c has become common in both private and public healthcare settings.

However, growing evidence shows that HbA1c may not always provide an accurate picture of blood glucose control in South Asian populations. Several biological, nutritional, and laboratory factors can affect its reliability. Understanding these limitations is important for both patients and healthcare providers in the region.

This article explains why HbA1c may sometimes be unreliable in India and Pakistan and discusses practical steps that can improve diabetes assessment.



What HbA1c Measures

HbA1c, or glycated hemoglobin, forms when glucose in the blood attaches to hemoglobin in red blood cells. Because red blood cells live for about 120 days, HbA1c reflects average blood sugar levels over that period.

An HbA1c level of 6.5% or higher is often used to diagnose diabetes. Levels between 5.7% and 6.4% are considered prediabetes. Doctors also use HbA1c to assess how well a patient’s diabetes is controlled over time.

The test is simple and does not require fasting. This makes it attractive in busy clinics. But the test assumes that red blood cells have a normal lifespan and normal hemoglobin structure. In many people in India and Pakistan, this assumption may not hold true.



High Prevalence of Anemia

Anemia is common in South Asia, especially among women and children. Iron deficiency anemia is widespread due to nutritional factors, frequent pregnancies, and limited access to balanced diets.

Iron deficiency can falsely raise HbA1c levels even when blood glucose is not high. The exact mechanism is not fully understood, but it appears that iron deficiency changes red blood cell turnover and glycation rates. As a result, a person without diabetes may show a higher HbA1c value.

When anemia is treated with iron supplements, HbA1c levels may decrease without any change in glucose levels. This can lead to confusion in diagnosis and treatment decisions.

In regions where anemia is common, relying only on HbA1c may result in overdiagnosis of diabetes.

Hemoglobin Variants and Thalassemia

India and Pakistan have a significant number of people with hemoglobin variants such as thalassemia traits and hemoglobin E. These inherited conditions alter the structure of hemoglobin.

Some HbA1c testing methods may give inaccurate results when hemoglobin variants are present. Depending on the laboratory method used, HbA1c values can be falsely high or falsely low.

Thalassemia trait, which is common in certain communities in both countries, often shortens the lifespan of red blood cells. If red blood cells live for a shorter period, they have less time to accumulate glucose. This can lead to falsely low HbA1c values even if blood sugar is elevated.

Without awareness of these factors, patients may be told their diabetes is under control when it is not.



Differences in Red Blood Cell Lifespan

HbA1c assumes that red blood cells survive for about 120 days. In reality, red blood cell lifespan can vary between individuals due to genetics, infections, chronic inflammation, and nutritional status.

Infections such as malaria and chronic conditions such as kidney disease can shorten red blood cell lifespan. In many rural and low-income settings in South Asia, such conditions are more common.

Shorter red blood cell survival reduces the time available for glycation. This may lower HbA1c values despite high glucose levels. On the other hand, reduced red blood cell turnover can increase HbA1c.

These variations mean that HbA1c does not always reflect true average glucose in these populations.



Impact of Chronic Kidney Disease

Chronic kidney disease is increasing in India and Pakistan, partly due to rising diabetes and hypertension rates. Kidney disease can influence HbA1c results.

Patients with kidney disease often have anemia and altered red blood cell turnover. Some may receive erythropoietin therapy, which stimulates the production of new red blood cells. A higher proportion of young red blood cells can lower HbA1c levels.

In such cases, HbA1c may underestimate actual blood glucose levels. Doctors managing patients with both diabetes and kidney disease should interpret HbA1c carefully.



Laboratory Variability and Standardization

Another concern is laboratory quality. While many urban laboratories follow international standards, smaller laboratories may not always use standardized methods.

Different HbA1c testing techniques can produce slightly different results. Inconsistent calibration and lack of quality control may increase variability.

In regions with limited resources, these technical factors can reduce reliability. Patients may receive different HbA1c values from different laboratories, leading to confusion.

Improving laboratory standardization and quality control is important for accurate diagnosis and monitoring.



Ethnic Differences in Glycation

Research suggests that different ethnic groups may have different glycation rates even at similar glucose levels. Some studies indicate that South Asians may have higher HbA1c levels compared to other populations at the same blood glucose concentration.

The reasons are not fully understood. Genetic factors and differences in red blood cell properties may play a role.

If this is confirmed, using the same HbA1c cutoffs for all populations may not be ideal. More region-specific research is needed to determine appropriate diagnostic thresholds for India and Pakistan.



Implications for Diagnosis

If HbA1c is falsely high, a person may be diagnosed with diabetes when they do not have it. This can cause stress, unnecessary medication use, and financial burden.

If HbA1c is falsely low, diabetes may go undetected. Delayed diagnosis increases the risk of complications such as nerve damage, kidney disease, and heart problems.

For these reasons, many experts recommend confirming diabetes diagnosis with fasting plasma glucose or an oral glucose tolerance test when results are borderline or inconsistent with symptoms.

In areas with high anemia or hemoglobin disorders, using multiple tests may improve accuracy.



Alternatives and Complementary Tests

Fasting plasma glucose and postprandial glucose tests remain useful tools. They measure blood sugar directly at a specific time.

The oral glucose tolerance test measures the body’s response to a glucose load. Although less convenient, it can provide valuable information when HbA1c results are uncertain.

Fructosamine is another test that reflects average glucose over two to three weeks. It is less affected by red blood cell lifespan but can be influenced by protein levels.

Continuous glucose monitoring is becoming more available in urban centers. It provides detailed glucose patterns and can help assess control more accurately.

Using a combination of tests may be the most practical approach in complex cases.



Practical Recommendations for Clinicians

Clinicians in India and Pakistan should consider the following steps:

1. Screen for anemia when interpreting HbA1c, especially in women and young adults.


2. Ask about family history of thalassemia or known hemoglobin disorders.


3. Confirm diagnosis with fasting or postprandial glucose if HbA1c does not match clinical findings.


4. Use the same laboratory for follow-up tests when possible to reduce variability.


5. Educate patients about the limitations of HbA1c.



These steps can improve patient care without adding excessive cost.



Guidance for Patients

Patients should understand that HbA1c is a helpful tool but not perfect. If test results seem unusual, they can discuss further evaluation with their doctor.

Maintaining a record of fasting and post-meal glucose readings can help provide a clearer picture. Addressing anemia and maintaining balanced nutrition can also support more accurate testing.

Patients with known hemoglobin disorders should inform their healthcare provider before testing.

Open communication between patient and doctor is important for effective diabetes management.



Need for Regional Research

There is a need for large, well-designed studies in South Asian populations to better understand how anemia, hemoglobin variants, and genetic factors affect HbA1c.

National guidelines may need to consider regional variations rather than relying entirely on data from Western populations.

Public health policies should also address anemia prevention, which will improve overall health and potentially enhance the reliability of diabetes testing.



Conclusion

HbA1c remains an important tool for diagnosing and monitoring diabetes. However, in India and Pakistan, several factors can reduce its reliability. High rates of anemia, hemoglobin variants, kidney disease, and laboratory variability all influence results.

Relying solely on HbA1c may lead to misdiagnosis or inaccurate assessment of glucose control. Combining HbA1c with other blood glucose tests and considering individual patient factors can improve accuracy.

A balanced approach that recognizes both the strengths and limitations of HbA1c is essential for effective diabetes care in South Asia.