• New research has identified a genetic variant amongst people of South Asian heritage that affects the accuracy of a common diabetes test, the HbA1c, which measures average blood sugar levels. 

• The HbA1c test, crucial for diagnosing type 2 diabetes, monitoring prediabetes, and guiding diabetes treatment, may give falsely lower results in South Asian people who carry this genetic variant, leading to delayed diagnosis. 

• In England alone, an estimated 32,000 South Asian people with diabetes and 17,500 with prediabetes may have underestimated blood sugar levels due to this variant. 

New research, which will be presented tomorrow at the Diabetes UK Professional Conference 2024, London, has discovered a genetic variant almost exclusive to people with South Asian heritage that affects the accuracy of the diabetes haemoglobin A1c (HbA1c) test.  

This test measures average blood sugar levels over the previous 2-3 months. It is crucial for diagnosing type 2 diabetes, monitoring prediabetes, and guiding diabetes treatment. South Asian people carrying this genetic variant may receive falsely lower HbA1c results, leading to delays in the diagnosis of type 2 diabetes. 

Using genetic and health data from the Genes & Health study¹ (over 60,000 individuals of Bangladeshi or Pakistani ethnicity living in England) and the UK Biobank (500,000 people of varied ethnicity living in the UK), Dr Miriam Samuel at Queen Mary University London and colleagues in the Genes & Health Research Team identified a genetic variant that is found in 7.6% of people of South Asian heritage but is ultra rare in other ethnicities.  

Individuals with this variant were found to have falsely lower HbA1c levels and differences in their full blood count. HbA1c tests estimate average blood sugar levels by measuring how much sugar is attached to haemoglobin in red blood cells. The research suggests that the genetic variant is linked to changes in red blood cells, and that this affects HbA1c test results. For those with two copies of the genetic variant (homozygous), HbA1c test results could be falsely lower by around 6 mmol/mol².  

The research team analysed health records of South Asian people carrying this genetic variant and found that those with one copy (heterozygous) were diagnosed with type 2 diabetes on average one year later, while those with two copies (homozygous) were diagnosed on average 2 years later, than those without the genetic variant. Inaccurate HbA1c results might also mean that people with the variant do not receive timely and appropriate treatments needed to manage blood sugar levels and reduce risk of long-term complications, which could include heart attacks, strokes, amputations, and sight loss. 

In England, it’s estimated that there are over 420,000 people from a South Asian background living with diabetes³ and over 230,000 have a diagnosis of prediabetes and are therefore at high risk of developing type 2 diabetes⁴. With around 7.6% of South Asians carrying this variant, this suggests that the HbA1c test is underestimating blood sugar levels in around 32,000 South Asian people with diabetes and 17,500 with prediabetes in England alone.  Thousands of prediabetes cases in South Asian people might have also been missed.  

The findings indicate that additional blood sugar testing, such as fasting glucose and oral glucose tolerance tests, and alternative monitoring pathways might be needed in South Asian people who carry the variant.  The researchers emphasise the importance of ethnic diversity in genetic research and recommend that further research is needed to explore whether inaccurate HbA1c results are contributing to the diabetes inequalities experienced by South Asian people living in the UK, which include increased risk of type 2 diabetes and of developing serious diabetes complications.  

Dr Miriam Samuel at Queen Mary University London said: 

“Many genetic variants linked to red blood cell conditions are ultra-rare amongst the Northern Europeans who have historically dominated genetic studies. We demonstrate one such variant that is carried by 7.6% of South Asians which could affect the accuracy of HbA1c and cause delays in diabetes diagnosis. Studies such as Genes & Health, focussing on populations who are underserved in genetic research, are vital to understand the different pathways that may contribute to diabetes inequalities in these communities.”  

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said:  

"This evidence showing that the accuracy of a common test to diagnose and monitor type 2 diabetes is linked to a person's ethnicity should be urgently investigated further. It's incredibly important that healthcare professionals are armed with a precise way to evaluate average blood sugar levels over extended periods. Without this, they are navigating in the dark and potentially at risk of overlooking cases of type 2 diabetes. Every individual at risk or with diabetes, regardless of their background, deserves equal access to effective diabetes care to live a healthy life and mitigate long-term diabetes complications.”