Unveiling Critical Limitations of the HbA1c Test in Indian Populations

India stands as the global epicenter of diabetes, with over 101 million adults living with the condition and another 136 million grappling with prediabetes, according to recent estimates. This staggering burden underscores the urgency for accurate diagnostic tools. Yet, a groundbreaking review published on February 8, 2026, in The Lancet Regional Health - Southeast Asia reveals a troubling flaw in one of the most trusted tests: glycated hemoglobin, commonly known as HbA1c. Titled "The limitations and fallacies of relying on glycosylated hemoglobin for diagnosing and monitoring diabetes in Indian populations," the study warns that sole dependence on HbA1c could delay type 2 diabetes diagnosis by a median of 4.1 years in certain cases, heightening risks of severe complications like retinopathy, nephropathy, and cardiovascular disease.

Led by Professor Anoop Misra from Fortis C-DOC Centre for Excellence for Diabetes in New Delhi, alongside experts from AIIMS New Delhi, Joshi Clinic Mumbai, and other institutions, this comprehensive analysis draws on decades of Indian data to challenge the status quo. It highlights how biological and laboratory factors prevalent in South Asia undermine HbA1c's reliability, urging a shift toward multiparametric testing strategies.

Understanding the HbA1c Test: How It Works and Its Global Role

The HbA1c test, or glycated hemoglobin test, quantifies the percentage of hemoglobin—a protein in red blood cells (RBCs) that carries oxygen—that has become coated with sugar molecules (glycated) due to prolonged exposure to high blood glucose levels. Since RBCs live about 120 days, HbA1c provides an average blood sugar reading over the past 2-3 months, making it convenient for both diagnosis and monitoring without fasting.

Globally, the World Health Organization (WHO) and American Diabetes Association (ADA) endorse an HbA1c level of 6.5% or higher as diagnostic for diabetes, 5.7-6.4% for prediabetes, and below 5.7% as normal. Its non-fasting nature has popularized it worldwide, especially in busy clinics. However, the Lancet review emphasizes that this "gold standard" falters significantly in Indian contexts due to unique physiological realities.

High Prevalence of Anemia and Its Impact on HbA1c Accuracy

Iron deficiency anemia (IDA), affecting 53% of Indian adults aged 19-59 and up to 64% in northern regions, profoundly distorts HbA1c. In IDA, RBC production ramps up with younger cells that glycate more readily, potentially inflating HbA1c falsely. Conversely, severe cases may prolong RBC lifespan, suppressing readings. A study of 116 young Pune adults showed HbA1c overestimating prediabetes in anemic individuals (23.3% vs. 7.8% by OGTT).

Hemolytic anemias, where RBCs die prematurely (lifespan <74 days), limit glycation time, yielding falsely low HbA1c despite hyperglycemia. These issues compound in rural India, where nutritional deficiencies prevail.

Hemoglobinopathies and G6PD Deficiency: Genetic Culprits in Misdiagnosis

India harbors a high burden of hemoglobinopathies like sickle cell disease/trait and thalassemia (prevalence 1.17-5.9%), where variant hemoglobins alter glycation kinetics, causing erratic HbA1c. Assays may misread these variants, leading to spurious highs or lows.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked enzyme disorder prevalent in 7.7-8.5% of Indians (higher in tribal areas, up to 27% in some groups), triggers subclinical hemolysis, shortening RBC lifespan and dropping HbA1c by ~0.9%. In South Asian men, this delays diabetes diagnosis by 4.1 years on average, raising microvascular complications by 37%. One in 63 South Asian males carries risky variants, amplifying national impact.

Professor Misra notes, "Relying exclusively on HbA1c can result in misclassification... delaying diagnosis or leading to overtreatment."

Evidence from Indian Studies: Stark Discordance with Gold Standard Tests

Multiple cohort studies expose HbA1c's shortcomings. In a South Indian cohort of 1,120 individuals, the oral glucose tolerance test (OGTT)—involving fasting plasma glucose (FPG) followed by 75g glucose load and 2-hour reading—flagged 87.8% prediabetes cases, while HbA1c caught only 45.4% (kappa concordance 0.09). North India's Chandigarh Urban Diabetes Study (1,972 participants) saw HbA1c missing 38-64% prediabetes under ADA/WHO cutoffs.

In 237 Northeast Indians with HbA1c <7%, 44% mismatched glucose metrics, linked to high red cell distribution width (RDW >17%). Seasonal fluctuations further confound: HbA1c peaks during monsoons, dips in autumn among 8,138 tracked patients.

National surveys leaning on HbA1c risk underestimating prevalence in anemia hotspots.Read the full Lancet study

The Real-World Consequences: Delayed Diagnosis and Surging Complications

Underdiagnosis fuels India's diabetes crisis, where 44% remain undetected. Delayed intervention by years elevates risks: neuropathy, vision loss, kidney failure, and heart attacks. G6PD carriers face 37% higher microvascular issues due to unchecked hyperglycemia.

• Missed prediabetes leads to 10-20% annual progression to diabetes.
• Poor glycemic control (HbA1c >8% in >50% patients) amplifies macrovascular events.
• Resource misallocation from flawed prevalence data hampers programs like National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases & Stroke.

Dr. Shashank Joshi warns of greater rural discrepancies: "In tribal areas, anemia and G6PD prevalence magnify errors."

Expert Recommendations: Toward a Multiparametric Approach

RSSDI and ICMR guidelines acknowledge HbA1c caveats, advocating combination testing. The Lancet proposes risk-stratified protocols:

• Primary care/low-resource: OGTT (FPG ≥126 mg/dL or 2hPG ≥200 mg/dL) + SMBG (2-3x/week, ₹450-750/month).
• Tertiary/high-resource: HbA1c + OGTT/CGM (Time in Range >70%) + fructosamine/glycated albumin (GA, unaffected by hemoglobin issues; available ~₹500-1000).
• Screen with CBC, RDW, iron studies, G6PD/electrophoresis if discordance.

Only 70% Indian labs are NGSP-certified for standardized HPLC assays; prioritize these.NGSP Certification Info Institutions like AIIMS drive such innovations; aspiring researchers can explore openings via research jobs.

Alternatives to HbA1c: Practical Options for Indian Settings

OGTT remains gold standard despite inconvenience. FPG offers quick screening but misses postprandial spikes. Emerging markers like fructosamine (2-3 week glycemia, ~₹660 home collection) and GA suit short-term needs, especially in anemia.

CGM/flash monitors track real-time trends, vital for high-risk patients. Dr. Samajdar advocates: "OGTT + SMBG refines estimates for better allocation."

Photo by Brett Jordan on Unsplash

Path Forward: Policy, Research, and Patient Empowerment

India needs tailored algorithms incorporating hematology, standardized labs, and OGTT-centric surveys. University-led research at AIIMS and beyond is pivotal; for careers in diabetes research, visit higher-ed-jobs or professor jobs.

Patients: Request CBC alongside HbA1c, track SMBG, consult endocrinologists. Early detection slashes complication risks by 50%.

This study spotlights academia's role in public health. Stay ahead with higher ed career advice on emerging fields like endocrinology research.