Study questions HbA1c threshold for type 2 diabetes diagnosis in young women

By Rebecca Jenkins

The glycated haemoglobin (HbA_1c) cut point for type 2 diabetes diagnosis may need to be re-evaluated in women aged under 50 years, a study suggests, but Australian experts have warned against overinterpreting the findings.

Using a dataset of more than one million people in England, researchers analysed the HbA_1c levels of 146,907 individuals who underwent a single test at one laboratory between 2012 and 2019 and had an HbA_1c of 50 mmol/mol or lower. They found women aged under 50 years old had an HbA_1c distribution markedly lower than that in men, by a mean of 1.6 mmol/mol.

‘The HbA_1c in these women lagged by up to 10 years compared to men aged under the age of 50,’ the researchers wrote in Diabetes Therapy.

The analysis was replicated in six laboratories with 938,678 individuals tested between 2019 and 2021 with similar findings.

‘We suggest that the threshold for diagnosis of diabetes mellitus may be too high by approximately 2 mmol/mol in women under the age of 50,’ they wrote.

‘We estimated an additional 17% (n=34,953) of undiagnosed women aged <50 years in England and Wales could be reclassified to have diabetes mellitus, which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years,’ they wrote.

Professor Jonathan Shaw, Deputy Director (Clinical and Population Health) at the Baker Heart and Diabetes Institute in Melbourne, said the researchers were arguing that HbA_1c levels were underestimating the true mean glucose in women, but did not have the data to fully support their conclusion.

‘There are other possible explanations including that women genuinely have a lower risk of diabetes than men. The lower prevalence of diabetes in women is also seen in studies that diagnose diabetes by blood glucose testing,’ he told Medicine Today.

‘To show that the HbA_1c threshold for diabetes is wrong for women, you need to show that the relationship of HbA_1c with either retinopathy or with some other measure of average glucose differs between men and women,’ he said.

Professor Anthony Russell, Director of Endocrinology and Diabetes at The Alfred in Melbourne, said HbA_1c cut offs have been determined based on when rates of diabetes complications increase.

‘This study would suggest in women under the age of 50, diabetes complications would be higher in women with a given HbA_1c compared with men – it would be interesting to see any data to support this,’ he told Medicine Today.

A review of databases comparing oral glucose tolerance test results (OGTT) and HbA_1c levels for women across a range of age ranges could provide further information, he added, particularly if it included data from different ethnic groups.

‘This would be more supportive and might provide further evidence to recommend a change in current practice,’ he said. 

Diabetes Ther 2023; https://doi.org/10.1007/s13300-023-01482-6.