Type 2 diabetes is being misdiagnosed in African Americans, genetic study suggests

Around 650,000 African Americans in the US have a unique genetic variant that significantly reduces the accuracy of the HbA1c blood test, meaning they could have undiagnosed type 2 diabetes

Type 2 diabetes is being misdiagnosed in African Americans, genetic study suggests


One of the tests used to diagnose type 2 diabetes and monitor blood sugar control is influenced by 60 genetic variants, an international team of scientists, including those from the Wellcome Trust Sanger Institute, has found. One genetic variant in particular, found only in African Americans, significantly reduces the accuracy of the HbA1c blood test used to diagnose and monitor the condition. This means around 650,000 African Americans in the US could have undiagnosed type 2 diabetes if tested with the HbA1c test alone.

The results, published today (12 September 2017) in PLOS Medicine suggest screening for the particular genetic variant alongside the diagnostic test, or using other diagnostic tests in populations with African ancestry in order to improve diagnoses of type 2 diabetes.

There are over 4 million* people living with diabetes in the UK, and this number is estimated to rise to 5 million by 2025. 90 per cent of these cases are type 2 diabetes, which is associated with increasing rates of obesity. In the US, the number of people with diabetes is more than 29 million**.

In the largest study of its kind, an international team of more than 200 scientists investigated genetic variants which are thought to affect the blood test used to diagnose and monitor type 2 diabetes, known as the glycated haemoglobin, or HbA1c test.

The team studied genetic variants in almost 160,000 people from European, African, East Asian and South Asian ancestries who were not known to have type 2 diabetes. Researchers discovered 60 genetic variants that influence the outcome of HbA1c tests, of which 42 variants were new.

One genetic variant in particular, in the G6PD gene, was found to significantly impact the results of the HbA1c test. The G6PD genetic variant is almost unique to people of African ancestry; around 11 per cent of African Americans carry at least one copy of this variant.

“The issue with the G6PD genetic variant is it artificially lowers the value of blood sugar in the HbA1c test, and can lead to under-diagnosis of people with type 2 diabetes. We estimate that if we tested all Americans for diabetes using the HbA1c test, we would miss type 2 diabetes in around 650,000 African Americans. However, the HbA1c test remains a suitable test for diagnosing and monitoring diabetes for the majority of people.”

Dr Inês Barroso, joint lead author from the Wellcome Trust Sanger Institute

The HbA1c test measures the amount of glucose, or sugar that is carried by the red blood cells in the body, for the previous two to three months.

“The G6PD genetic variant shortens the three-month lifecycle of red blood cells. So in African Americans who have this variant, their red blood cells don’t live long enough to bind to the glucose in the blood. Therefore these people will have a lower level of HbA1c, which won’t show as a positive result for type 2 diabetes.”

Dr Eleanor Wheeler, joint first author from the Wellcome Trust Sanger Institute

“We now need further studies involving people of diverse ancestries to assess how diagnostic tests for diabetes should be altered to account for genetic variation. In the meantime, an option would be to genetically screen African Americans for the G6PD variant alongside the HbA1c test in order to accurately diagnose type 2 diabetes, or use other diagnostic tests such as fasting glucose measurements. We suggest moving towards precision medicine to take people’s genetics into account and improve diagnosis and monitoring for diabetes.”

Dr James Meigs, joint lead author from Massachusetts General Hospital and Harvard Medical School

Notes to Editors
  • Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

    Wheeler E, Leong A, Liu CT, Hivert MF, Strawbridge RJ et al.

    PLoS medicine 2017;14;9;e1002383


* Taking into account the number of people likely to be living with undiagnosed diabetes http://www.diabetes.co.uk/diabetes-prevalence.html

** https://www.cdc.gov/features/diabetesfactsheet/

Patient enquiries:

Contact the Diabetes UK Helpline for specialist information and advice on all aspects of living with diabetes.
Call: 0345 123 2399*, Monday to Friday, 9am–6pm, Email: helpline@diabetes.org.uk

If you're in Scotland:
Call: 0141 212 8710*, Monday to Friday, 9am–6pm, Email: helpline.scotland@diabetes.org.uk


This work was supported by the American Diabetes Association, the National Institutes of Health, Wellcome and many others. For full funding information, please see the publication.

Selected Websites
Genome-wide association studiesStoriesGenome-wide association studies
Genome-wide association studies have led to the discovery of hundreds of genes with a role in common diseases.

What is a complex disease?FactsWhat is a complex disease?
Many common diseases are influenced by a combination of multiple genes and environmental factors. These diseases are referred to as complex diseases.

Contact the Press Office

Emily Mobley, Media Manager

Tel +44 (0)1223 496 851

Dr Samantha Wynne, Media Officer

Tel +44 (0)1223 492 368

Dr Matthew Midgley, Media Officer

Tel +44 (0)1223 494 856

Wellcome Sanger Institute,
CB10 1SA,

Mobile +44 (0) 7748 379849

Recent News

Appointments and changes to the Genome Research Limited Board
At the GRL Board meeting on 2 December 2019, David Willetts announced his intention to step down as Chair because of his extensive commitments across the academic and science sectors. Wellcome's Director, Jeremy Farrar, will take over the Chair of GRL Board from 1 January 2020.
Researchers identify new possibilities for the treatment of inflammatory bowel disease
Two molecular pathways found to be integral to maintaining balance in the digestive system
Root of childhood kidney cancer discovered
Pre-cancerous signatures found in healthy tissue point the way towards new treatment options