Is the Current Cut Point for Glycated Haemoglobin (HbA1c) Correct for Diagnosing Diabetes Mellitus in Premenopausal Women? Evidence to Inform Discussion

Holland, David; Fryer, Anthony A.; Stedman, Mike; Hanna, Fahmy W. F.; Duff, Christopher J.; Green, Lewis; Scargill, Jonathan; Halsall, Ian; Gaskell, Neil; Howe, Jonathon D.; Heald, Adrian H.; Wu, Pensee

Abstract

Women are on average diagnosed with diabetes mellitus at later age than men but have higher mortality. As the diagnosis of diabetes mellitus is primarily based on HbA1c, the use of a non-specific reference range and cut point for diabetes mellitus that does not account for gender differences in diabetes could potentially lead to underdiagnosis of diabetes mellitus in women and missed opportunities for intervention. We investigated whether a contributing factor to the later diagnosis in women may be a difference in distribution of HbA1c in premenopausal women versus men of the same age by comparing HbA1c values in men and women across multiple sites in the UK. We analysed the HbA1c levels of 146,907 individuals who underwent single testing only and had HbA1c ≤ 50mmol/mol between 2012 and 2019 in one laboratory (cohort1). This was replicated in six laboratories with 938,678 individuals tested between 2019 and 2021 (cohort2). In cohort1, women < 50years old had an HbA1c distribution markedly lower than that in men by a mean of 1.6mmol/mol (p < 0.0001), while the difference in the distribution of HbA1c for individuals aged ≥ 50years was less pronounced (mean difference 0.9mmol/mol, p < 0.0001). For individuals under the age of 50, HbA1c in women lagged by up to 10years compared to men. Similar findings were found in cohort2. We estimated an additional 17% (n = 34,953) of undiagnosed women aged < 50years 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 16-50years. The HbA1c cut point for diagnosis of diabetes mellitus may need to be re-evaluated in women under the age of 50years. Early identification of diabetes mellitus in women has the potential to improve women's health outcomes in the longer term. [Abstract copyright: © 2023. The Author(s).]

• Journal Article Type: Article
• Acceptance Date: Sep 26, 2023
• Online Publication Date: Sep 30, 2023
• Publication Date: Sep 30, 2023
• Deposit Date: Oct 2, 2023
• Journal: Diabetes Therapy
• Print ISSN: 1869-6953
• Electronic ISSN: 1869-6961
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1007/s13300-023-01482-6
• Keywords: Epidemiology, Haemoglobin A1c, Diabetes mellitus, Diagnostic controversies, Sex difference
• Additional Information: Received: 28 August 2023; Accepted: 26 September 2023; First Online: 30 September 2023; : ; : All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.; : The study was in accordance with the Declaration of Helsinki. This study is part of an audit and quality improvement programme to increase the quality of laboratory test requesting. Hence, it includes a service evaluation and audit of local practice against the guidelines outlined by NICE with a view to increasing implementing quality improvements to enhance the clinical laboratory service. Accordingly, this study was not considered to be research using the decision tool provided by the UK Health Research Authority and did not require NHS Research Ethics Committee review.