HbA1c Alone Not Reliable for Diabetes Diagnosis in Indian Population: Study

A new research published in in Lancet Regional Health: Southeast Asia has warned that the glycated haemoglobin (HbA1c) test which is used a sole diagnostic or monitoring tool for type 2 diabetes may not accurately reflect blood glucose levels for millions of Indians, particularly in regions with high prevalence of anaemia, hemoglobinopathies, and red blood cell enzyme (G6PD) deficiency. The study led by professor Anoop Misra questions the reliance on HbA1c test as a standalone tool for diagnosing and monitoring diabetes in Indian and South Asian populations.

The study mentions that any condition that affects the quantity, structure, or lifespan of haemoglobin—such as anaemia, hemoglobinopathies, or other red blood cell disorders—can distort HbA1c values and lead to misleading estimates of average blood glucose.

“Relying exclusively on HbA1c can result in misclassification of diabetes status. Some individuals may be diagnosed later than appropriate, while others could be misdiagnosed, which may affect timely diagnosis and management. Similarly, monitoring of blood sugar status may be compromised”. said Professor Anoop Misra, corresponding author and Chairman of Fortis C-DOC Center of Excellence for Diabetes.

The study highlights that the widespread use of this test and the tendency toward oversimplification by both physicians and patients can lead to misinterpretation, particularly in populations with altered erythrocyte dynamics, such as those with anaemia or hemoglobinopathies.

According to the study the assumption that HbA1c uniformly reflects glycaemic control across all individuals, regardless of genetic, hematologic, or metabolic variation, is increasingly difficult to justify in some populations, such as Asian Indians.

 “Even in well-resourced urban hospitals, HbA1c readings can be influenced by red blood cell variations and inherited haemoglobin disorders. In rural and tribal areas, where anaemia and red cell abnormalities are common, the discrepancies may be greater,” Shashank Joshi, co-author from Joshi Clinic, Mumbai stated.

The study highlighted that HbA1c may under- or overestimate blood glucose in populations with high rates of low blood counts (anaemia), inherited blood disorders (abnormal haemoglobin), or enzyme problems like G6PD deficiency anaemia, hemoglobinopathies. In some regions of India people are nutritionally challenged which can distort HbA1c readings. This would affect both diagnosis and monitoring thus misleading clinicians.

The study revealed that reliance on HbA1c alone could delay diagnosis by up to four years in men with undetected G6PD deficiency, which can increase the risk of complications. In addition, inconsistent quality control across laboratories can further affect HbA1c accuracy, making interpretation challenging. It further disclosed that public health surveys based solely on HbA1c may misrepresent India’s diabetes burden.

The authors of the study have recommended an approach to glycaemic monitoring.  They have outlined a resource-adapted framework for India: in low-resource settings, oral glucose tolerance test (2 glucose values, one fasting and another 2 hours after ingesting 75 gm glucose) for diagnosis, and for monitoring self-monitoring of blood glucose (SMBG, using glucose meters) 2-3 times weekly combined with basic hematologic screening (haemoglobin, blood smear) is recommended.

In tertiary care settings, combination of HbA1C (done with standard equipment) with OGTT for diagnosis and for monitoring, continuous glucose monitoring (CGM) with alternative markers like fructosamine.

When needed, comprehensive iron studies, haemoglobin electrophoresis, and quantitative G6PD testing are advised.  The framework emphasizes that monitoring intensity and biomarker selection should be tailored to healthcare resources and patient risk factors, with particular attention to populations where anaemia, hemoglobinopathies, and G6PD deficiency are prevalent.

The study stressed that in regions where anaemia from various causes is endemic (such as India), glycosylated haemoglobin (HbA1c), being derived from haemoglobin and widely regarded as the gold standard for monitoring diabetes, may give spurious values. Therefore in many cases, it should be combined with other tests for the diagnosis and monitoring of diabetes.