Standard Diabetes Test May Mislead Diagnosis and Monitoring in South Asian Populations, New Analysis Warns

▴ Fortis C-DOC
Lancet Regional Health – Southeast Asia study reveals HbA1c limitations in populations with prevalent anemia, hemoglobinopathies, and G6PD deficiency.

9th February, New Delhi, India: A new evidence-based Viewpoint published online in  Lancet Regional Health: Southeast Asia highlights that the widely used glycated hemoglobin (HbA1c) test, as available in India, may not accurately reflect blood glucose levels for millions of Indians, particularly in regions with high prevalence of anemia, hemoglobinopathies, and red blood cell enzyme (G6PD) deficiency. Led by Professor Anoop Misra and collaborators, the review questions reliance on HbA1c as a sole diagnostic or monitoring tool for type 2 diabetes in South Asia. HbA1c measurements primarily reflect the glycation of hemoglobin. Any condition that affects the quantity, structure, or lifespan of hemoglobin—such as anemia, 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,” said Professor Anoop Misra, corresponding author and Chairman of Fortis C-DOC Center of Excellence for Diabetes. “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.”

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

Dr. Shambho Samrat Samajdar, co-author from Kolkata, emphasized a comprehensive approach: “Combining oral glucose tolerance test, self-monitoring of blood glucose, and hematologic assessments provides a more accurate picture of diabetes risk. This approach can help refine public health estimates and guide resource allocation.”

 

Key findings from the review include:

·                     HbA1c may under- or overestimate blood glucose in populations with high rates of low blood counts (anemia), inherited blood disorders (abnormal hemoglobin), or enzyme problems like G6PD deficiency anemia, hemoglobinopathies.

·                     In some regions of India ( more than 50% population in some regions, data from 2025), people are nutritionally challenged with widespread have iron deficiency anemia, which can distort HbA1c readings.

·                     This would affect both diagnosis and monitoring thus misleading clinicians.

·                     Reliance on HbA1c alone could delay diagnosis by up to 4 years in men with undetected G6PD deficiency, potentially increasing risk of complications.

·                     In addition, inconsistent quality control across laboratories can further affect HbA1c accuracy, making interpretation challenging

·                     Public health surveys based solely on HbA1c may misrepresent India’s diabetes burden.

 

Recommended Approach to Glycemic Monitoring

1.                   The authors outline 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 (hemoglobin, blood smear) is recommended.

2.                   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.

3.                   When needed, comprehensive iron studies, hemoglobin electrophoresis, and quantitative G6PD testing are advised.

4.                   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 anemia, hemoglobinopathies, and G6PD deficiency are prevalent.

Summary: In regions where anemia from various causes is endemic (such as India), glycosylated hemoglobin (HbA1c), being derived from hemoglobin and widely regarded as the gold standard for monitoring diabetes, may yield spurious values; therefore, in many cases, it should be combined with other tests for the diagnosis and monitoring of diabetes.

About the Authors:

·                     Anoop Misra, MD – Chairman, Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi.

·                     Shashank R Joshi, MD DM (Endocrinology) – Department of Endocrinology, Joshi Clinic, Mumbai.

·                     Shambo Samrat Samajdar, MD DM (Clinical Pharmacology) – Department of Out-Patient Clinic, Diabetes and Allergy-Asthma Therapeutics Specialty Clinic, Kolkata

·                     Dr Naval K Vikram, MD, Professor of Medicine, All India Institute of Medical Sciences, New Delhi

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