Why a ‘normal’ HbA1c may not mean you’re safe from diabetes

In the heart of New Delhi, at the bustling Fortis C-DOC Centre for Excellence, Dr. Anoop Misra—renowned endocrinologist and diabetologist, and executive chairman of Fortis C-DOC Hospital for Diabetes and Allied Sciences—stared at a patient’s chart that defied common medical logic. The patient, a 45-year-old man from a tribal community in Madhya Pradesh, had a glycated hemoglobin (HbA1c) reading of 5.8%. In most clinical guidelines, this would suggest a state of prediabetes: concerning, but not yet critical. However, the man’s Fasting Plasma Glucose (FPG) was consistently high, and he was already showing early signs of retinopathy.FPG is a blood test that measures blood sugar levels after a person has not eaten or consumed anything besides water for 8 to 12 hours. It is among the most common diagnostic tools used to screen for prediabetes and diabetes. Diabetic retinopathy, or damage to the retina, is also one of the leading causes of vision loss among diabetic patients.Something wasn’t adding up. More worrying was the fact that this discrepancy was not an isolated incident; it became the catalyst for a deep dive into what Dr. Misra and his colleagues—along with Shambo Samrat Samajdar (well-known clinical pharmacologist), Dr. Shashank R. Joshi (endocrinologist, diabetologist and medical researcher), and Dr. Naval K. Vikram (diabetologist and a professor at AIIMS)—described as 'The limitations and fallacies of relying on glycosylated hemoglobin for diagnosing and monitoring diabetes in Indian populations' in The Lancet Regional Health – Southeast Asia. Here is what they found.Though HbA1c is widely used across the world to diagnose and monitor type 2 diabetes, its accuracy in India and South Asia can be affected by common conditions such as anemia, blood disorders, and G6PD deficiency. Poor standardization of HbA1c testing across laboratories also adds to the problem. Because of this, experts say HbA1c alone should not be relied on for diabetes diagnosis and monitoring in India. Instead, doctors should use a combination of tests—including the Oral Glucose Tolerance Test (OGTT), regular blood sugar monitoring, and, where possible, Continuous Glucose Monitoring (CGM)—along with basic blood tests. This approach can help improve diagnosis, treatment, and patient care, especially in rural and resource-limited settings.For decades, HbA1c had been considered the “gold standard” for diagnosing and monitoring type 2 diabetes because it does not require fasting and reflects average glucose levels over three months. But as this Lancet study shows, in India, a massive “glycation gap” is emerging. Dr. Misra realised that for many South Asians, the HbA1c test could be like looking through a distorted lens.The reason lies in the very blood cells being measured. India carries a heavy burden of hematological abnormalities that silently alter how sugar attaches to hemoglobin. Iron deficiency anemia (IDA), which affects an estimated 53% of Indian adults, can falsely elevate HbA1c levels, leading to overdiagnosis. Conversely, conditions like G6PD deficiency—prevalent in nearly 8.5% of the population—shorten the lifespan of red blood cells. Because these cells do not live long enough to “collect” sugar, they can produce falsely low HbA1c readings.Says Dr. Misra, head of the Diabetes Foundation of India: “HbA1c is made from hemoglobin, and any condition that affects hemoglobin jeopardises the interpretation of HbA1c. In this context, the most widespread reason in India would be anemia. But hereditary hemoglobin disorders also exist in many parts of our country. In such cases, it is best to take the help of blood glucose levels using glucose meters. It is important to emphasize that oral glucose tolerance tests using blood glucose values should be used for diagnosis of diabetes and not HbA1c for Indians.”The research has reignited debate over the reliability of HbA1c in Indian populations, especially since conditions such as anemia, iron deficiency, thalassemia, and other blood disorders are far more common in South Asia than in many Western countries.“The issue is of major clinical importance because India is already carrying one of the world’s heaviest diabetes burdens,” says Dr. Nishant Raizada, HOD, endocrinology and diabetes, Amrita Hospital. “We use HbA1c extensively because it gives an average of blood sugar levels over nearly three months. But there are several biological and genetic factors in many Indian patients that can affect the accuracy of this reading,” he adds.HbA1c measures the amount of glucose attached to hemoglobin, the protein in red blood cells that carries oxygen. The problem, experts say, is that anything that changes the lifespan of red blood cells will also change the result. “For example, iron deficiency anemia can falsely elevate HbA1c levels even if glucose levels are not very high. Other conditions such as thalassemia, G6PD deficiency, kidney disease, liver disease, pregnancy, or rapid turnover of red blood cells can falsely lower HbA1c,” says Dr. Raizada.India has one of the world’s largest populations affected by anemia. According to the National Family Health Survey (NFHS-5), more than half of Indian women are anaemic. That makes the discussion especially relevant in routine diabetes screening. Some doctors believe this may explain why some people show symptoms of uncontrolled diabetes despite “normal” HbA1c reports, while others appear diabetic on paper but have relatively stable real-time glucose patterns.In the case of the patient from Madhya Pradesh, a later genetic test revealed that he was carrying a G6PD variant. This “silent” condition had masked his true glucose levels for years, causing a delay of more than four years in diagnosis and significantly increasing his risk of microvascular complications.As Dr. Misra collaborated with experts such as Dr. Shashank Joshi in Mumbai, Dr. Naval Vikram in New Delhi, and Dr. Shambo Samrat Samajdar in Kolkata, the scale of the problem became clearer. A study of more than 1,100 adults in South India found that the Oral Glucose Tolerance Test (OGTT) identified prediabetes in nearly 88% of participants, while HbA1c identified only 45%. The two tests were barely speaking the same language.In North India, researchers found that standard ADA cut-offs, or specific blood sugar thresholds, were missing a staggering number of cases. They suggested that for the Indian population, an HbA1c threshold of 6.3% might be more appropriate for diagnosis. Even then, however, it should not be used alone.The researchers identified several common “HbA1c disruptors” in India:The researchers knew that oversimplification—by both doctors and patients—could be dangerous. They therefore proposed a “multiparametric, risk-stratified approach.”For patients in resource-limited rural settings, they advocated a return to the basics: OGTT and regular self-monitoring of blood glucose (SMBG). In these regions, where IDA and G6PD deficiency often go undiagnosed, HbA1c was simply too unreliable to serve as the sole marker of health.In high-resource tertiary centres, they recommended advanced markers such as:Experts stress that this does not mean HbA1c should be discarded. Diabetes care is becoming more layered and personalised, not less.“The future of diabetes management is not about relying on one test alone. We are increasingly combining HbA1c with fasting sugar, post-meal sugar, Continuous Glucose Monitoring Systems (CGMS), and sometimes alternative markers such as fructosamine or glycated albumin,” says Dr. Raizada.Doctors also point out that Indians develop diabetes at younger ages, with more abdominal fat and greater metabolic risks at lower BMIs than many Western populations. This makes accurate diagnosis even more critical.“What we are saying is not that HbA1c is wrong. It is still one of the most valuable tools for diabetes care in the world. But Indian patients need to understand that medicine is moving towards precision care, where the patient matters more than a single number,” says Dr. Raizada.The implications of these findings are not just clinical; they also affect diabetes testing and healthcare policy at a national level. Surveillance programmes relying solely on HbA1c may be misestimating the true prevalence of diabetes in India, potentially leading to major misallocation of public health resources.Dr. Misra’s team has called for mandatory standardisation of HbA1c assays across India’s thousands of laboratories, many of which continue to use non-certified methods. They also argued that every diabetes workup should include a basic hematological screening—checking for red cell distribution width (RDW) and ferritin—to ensure that the HbA1c reading actually reflects what doctors think it does.The story of diabetes in India is no longer just about blood sugar. It is also about the complex interplay of genetics, nutrition, and hematology. By looking beyond a single number, the Lancet study is paving the way for a more precise and individualised form of medicine.“Precision medicine is an attractive concept for the future because it can yield greater health benefits. But the challenge is that it may not be easily applicable for people from middle- and low-income backgrounds because of the additional costs involved,” says Dr. Misra.This shift also reflects a larger transformation in Indian healthcare towards precision medicine, where treatment is tailored to a patient’s biology, genetics, lifestyle, nutrition, and risk profile rather than relying on a one-size-fits-all model. For diabetes patients in India, this could be especially important because Indians often develop diabetes younger, at lower BMIs, and with different metabolic risks than Western populations.As the sun set over the clinic in New Delhi, the doctor updated the tribal patient’s treatment plan—not based on a flawed percentage, but on a more comprehensive understanding of his biology. The “fallacy” of HbA1c had been exposed, replaced by a clearer and safer path toward managing a national epidemic.The challenge now is making precision medicine affordable and accessible to all.Medical experts consultedThis article includes expert inputs shared with TOI Health by: Dr Anoop Misra, executive chairman of Fortis C-DOC Hospital for Diabetes and Allied SciencesDr. Nishant Raizada, HOD, endocrinology and diabetes, Amrita Hospital