By Dr. David Chandy, Director of Endocrinology and Diabetology at Sir H.N. Reliance Foundation Hospital.

In the past, the use of HbA1c levels to improve diabetes diagnosis and monitoring has dominated the diabetic landscape. It is convenient, requires no fasting, and provides a detailed history of how the body has been controlling its blood glucose levels. However, with the recent publication of a study in The Lancet, the uncomfortable truth about the use of HbA1c levels in some clinical environments in India has resurfaced.

India faces high rates of anemia, iron deficiency, abnormalities of hemoglobin itself, chronic kidney disease, as well as nutritional deficiencies. These are factors which directly challenge the biological assumptions used in the HbA1c test. Where the life cycle of the red blood cell or the composition of the hemoglobin is abnormal, the reading for blood glucose can be over- or underestimated. It is not an insignificant problem.

In practical application, HbA1c is frequently used as a standalone diagnostic tool to categorize patients as diabetic or non-diabetic. However, the Lancet study cautioned against the misdiagnosis of patients and the attendant disease delays, particularly in communities where anemia is prevalent amongst women, children, the elderly, and socioeconomically disadvantaged groups.

Clinically, the question is no longer whether HbA1c is of use, but what to do when HbA1c reliability is impaired.

Why HbA1c Alone is Not Sufficient in India

HbA1c is an estimate of average blood glucose levels over the past two to three months by measuring the amount of glucose present in combination with hemoglobin. However, this is based on the assumption of normal red blood cell turnover rates. But this often does not occur in India.

Iron deficiency anemia causes falsely increased HbA1c levels, and lower HbA1c levels are seen in patients with hemolytic anemia and chronic kidney disease. This presents as an increased risk for diabetic complications. For example, patients diagnosed with “well-controlled diabetes” and “non-diabetic anemia” clearly did not present that way clinically.

The reality being experienced is what matters; when diagnostic tests fail to measure up, doctors must rely on physiology, rather than convenience.Plasma glucose testing. Plasma glucose testing must regain its central importance. In

The Lancet study again underscores an important, though often overlooked, basic fact: plasma glucose measurements are by far the most direct and accurate method of assessing glycaemia, especially in cases of dubious HbA1c values.

Fasting Plasma Glucose (FPG): A Practical First Step

Fasting plasma glucose levels are simple, inexpensive, and widely available in any part of India. However, most importantly, FPG does not require any interference from abnormalities of red blood cells.
It is effective in routine screening and early detection.
It detects normal hyperglycemia that Hb1c may miss to detect in patients with anemia.
It is well suited for primary care use and population screening.

It should also be used to assess patients with recognized or suspected anemia, and verify FPG determinations made using HbA1c.

Oral Glucose Tolerance Test (OGTT): Still the Most Sensitive Tool

Though the OGTT, where 2 hours after glucose ingestion, is an understated diagnostic technique owing to time and other limitations, still, it remains the most accurate means for detecting diabetes and prediabetes in their early stages.

It is particularly relevant to India, since even the “thin-fat" metabolic profile carries with it a risk of developing insulin resistance without obesity being a factor.

OGTT is particularly useful when assessing:

Lean people with good family background
Women who have had gestational diabetes in the past
Patients with normal HbA1c but persisting symptoms
Younger adults, who disease progression can be modified through early intervention

Discordance between HbA1c and clinical suspicion justifies the OGTT to be considered as an essential diagnostic criterion and not optional.

Random Plasma Glucose: Clinical Symptoms Still Matter

Testing of random plasma glucose carries considerable diagnostic weight in the presence of classic symptoms, such as polyuria, polydipsia, unexplained weight loss, and fatigue.

A high random glucose value in the presence of symptoms should promptly lead to diagnosis and initiation of treatment without waiting for HbA1c values. This will avoid undue delay, particularly at the outpatient and acute care settings.

Moving Toward a Multi-Parameter, Physiology-Based Approach

The key takeaway from this Lancet study is: Don't stop using HbA1c, but stop believing that it's completely right.

Indian clinicians will need to accept a multi-parameter diagnostic system which will comprise:

Plasma glucose levels - FPG, OGTT, or random glucose
Clinical symptoms and patient history
Anemia status and nutritional assessment
Renal function and Comorbidities

The results of such an approach involve diagnosis in line with the physiological reality of the patient rather than some single biochemical marker.

Implications for Healthcare Delivery in India

From a systems perspective, this overreliance on HbA1c has wider implications for a health system, with potential misclassifications resulting in suboptimal pathways of care, delayed interventions, and increased risk of complications, furthering a burdened health care system.

Thus, there is no need to re-emphasize plasma glucose tests, but there is need to update thinking, reinforce guidelines, and raise physicians' awareness of specific population risks.

The Way Forward

To begin with, as the disease becomes even more prevalent in India, the precision in diagnosis may be as important as its treatment. The study in "The Lancet" serves as a timely reminder of the need to tailor tests so they suit the epidemiological context, rather than the tests being uniform in application.

For doctors, the solution calls for striking a balance between efficiency and accuracy, carefully utilizing HbA1c tests, and corroborating them with plasma glucose tests when treating anemia, and a comprehensive and patient-centered approach.

Thus, clinicians have the opportunity to address earlier detection, timely intervention, and the best outcomes for millions of people at risk.

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