Researchers have suggested lowering HbA1c cut-offs for premenopausal women, but Australian GPs say more investigation is needed.
The threshold for diagnosis of type 2 diabetes should be lowered for women under 50 because menstruation may be affecting their blood sugar.
That is according to fresh research out of the UK, suggesting differences in HbA1c levels due to haemoglobin replacement linked to menstrual blood loss could result in missed diabetes diagnoses, with the authors proposing that a lower diagnosis point may be appropriate.
To reach their findings, the researchers examined HbA1c testing across seven laboratory sites representing 5% of the UK’s population, finding that women younger than 50 years had an HbA1c distribution ‘markedly lower’ than in men, by a mean of 1.6 mmol/mol. In these women, average HbA1c levels fell behind by around five years compared to men in the same age group.
‘Early identification of diabetes in women has the potential to improve health outcomes in the longer term,’ they concluded.
But in Australia, two experts are not convinced by the study’s findings.
Dr Gary Deed is Chair of RACGP Specific Interests Diabetes. He told newsGP while the outcomes are interesting, the study is observational and has inherent limitations.
‘Making broad population health conclusions is difficult to justify at this stage,’ he said. ‘It needs to be replicated across different populations and different countries to truly get an accurate insight.
‘The difference in HbA1c in women aged under 50 may not have any long term-health implications.
‘Suggesting changing the thresholds for diagnosis have huge economic and health impacts, let alone impacts for the person thus diagnosed through any such change.’
With diagnosis of type 2 diabetes ‘primarily’ based on HbA1c regardless of age or sex, the researchers analysed whether menstruation-related differences in blood sugar control could be contributing to women being diagnosed at a later age and having higher mortality.
But Dr Deed believes this is one of the study’s limitations.
‘The authors focus on HbA1c, but we know that diabetes can be diagnosed by different methods, including fasting BGL [blood glucose level] and an oral glucose tolerance test,’ he said.
‘It would have been best if these authors had combined different methods to confirm the accuracy – sensitivity and specificity – of any single diagnostic pathway.
‘It reminds me of the change in the thresholds and methods to diagnose gestational diabetes some years ago and the ongoing debate about the significant rise in diagnosis and management for women with gestational diabetes who previously would have not required any such health impositions.’
GP and women’s health expert, Associate Professor Magda Simonis, sides with Dr Deed’s hesitancy regarding the study’s outcomes, emphasising there are other factors to consider.
‘Making the association between menstruation and blood glucose levels seems like a long stretch,’ she told newsGP.
‘Of interest is that women under 50 with type 2 diabetes tend to receive a diagnosis later in life than men. It is important to acknowledge that polycystic ovarian syndrome [PCOS] is the commonest endocrine disease affecting up to one in eight women during their reproductive lifetime, it takes an average of up to 12 years to diagnose and if diagnosed, is associated with a 50% risk of developing type 2 diabetes.
‘There is evidence that throughout women’s lifetime, there is increased insulin resistance and therefore this might have implications for their health, rather than menstruation itself.’
The study, an exploratory analysis comprising a total of 938,678 people, was conducted in two cohorts:
- One laboratory tested between 2012 and 2019 to assess the sex and age differences of HbA1c in individuals who underwent single testing only, had not been diagnosed with diabetes, and had an HbA1c result of <48 mmol/mol, the cut off for diagnosing diabetes
- The process was replicated in the second cohort, with results taken from six laboratories in which individuals were tested between 2019 and 2021
‘We estimated an additional 17% of undiagnosed women aged under 50 years could be reclassified to have diabetes,’ the authors state.
‘Our findings provide evidence that the HbA1c cut point for diagnosis of type 2 diabetes need to be re-evaluated in women under the age of 50.’
However, Associate Professor Simonis, who is also a member of the RACGP Expert Committee – Quality Care, argues that instead, women’s health should be managed better.
‘It starts by applying a gender and intersectional lens to health, educating the public and the health sector around menstrual patterns and taking a thorough menstrual history,’ she said.
‘Irregular and sparse periods might point to, for example, a higher risk for PCOS in women, and therefore early intervention can prevent the long-term sequelae and address the disparity in cardiovascular risk factor management between men and women.’
Associate Professor Simonis recommends following existing RACGP Red Book guidelines related to diabetes screening before and during perimenopause, which include the 40–43-year-old fasting blood glucose screen and the 45–49 fasting lipids and health screen.
‘Undertaking these screens routinely at these stages in life will help capture women under 50 with type 2 diabetes who may not be being diagnosed early enough,’ she said.
But for now, both Dr Deed and Associate Professor Simonis believe it would be premature to adjust diabetes diagnosis thresholds based on a link between menstruation and blood glucose levels.
‘[This is] certainly an interesting observational analysis,’ Dr Deed said.
‘But needing more effort from researchers to confirm concerns before drawing conclusions.’
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