The role of menstruation in type 2 diabetes diagnosis

The diagnosis threshold for type 2 diabetes (T2D) should be lowered in women aged under 50 years, since natural blood loss through menstruation could be affecting their blood sugar management. This is according to the study by Dr Adrian Heald, Salford Royal Hospital, UK, and colleagues presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany (2–6 October) and published in the journal Diabetes Therapy.

Analysis of the national diabetes audit results has shown that women of younger age with T2D seem to have a higher mortality rate than men. The underlying mechanisms remain unclear. However, it is known that women are on average diagnosed with T2D at a later age than men.

In this new study, the authors investigated whether a contributing factor to this late diagnosis may be a sex difference in the levels of glycated haemoglobin (HbA1c - a standard measure of blood sugar control) due to haemoglobin replacement linked to menstrual blood loss.

The authors examined HbA1c testing across seven UK laboratory sites (representing 5% of UK population), conducting an exploratory analysis in two cohorts. Cohort 1 was from one laboratory tested between 2012 and 2019 (146,907 participants). Researchers assessed the sex and age differences of HbA1c in individuals who underwent single testing only, that had not been diagnosed with diabetes and had an HbA1c result of equal to or less than 48 mmol/mol (the cut-off for diagnosing diabetes). The process was replicated in cohort 2 results from six laboratories with individuals tested between 2019 and 2021 (total people included 938,678).

At 50 years, average HbA1c levels in women lag by approximately 5 years compared to men, according to the study. The data found women aged under 50 years old had an HbA1c distribution that was lower than that of men while the difference in the distribution of HbA1c for individuals aged 50 years and over was less pronounced.

Additional analysis showed that at HbA1c of 48 mmol/mol, 50% fewer women could be diagnosed with T2D than men under the age of 50, while only 20% fewer women could be diagnosed with T2D than men over or equal to the age of 50. These findings were consistent with those in cohort 2.

Based on these observations, the authors estimated the effects of lowering the threshold for diagnosis of diabetes from HbA1c (48 mmol/mol) by 4.2% to 46 mmol/mol for women under the age of 50. This analysis showed that an additional 35,345 currently undiagnosed women in England would be reclassified as being diagnosed with T2D (17% more than the current 208,000 recorded women with T2D aged under 50 years).

The authors also highlight that sex and gender difference in adverse cardiovascular risk factors are known to be present prior to the development of T2D. Once diagnosed, the prevalence of atherosclerotic cardiovascular disease is twice as high in patients with diabetes mellitus compared to those without diabetes mellitus. For women, diabetes mellitus is a stronger risk factor for cardiovascular disease than for men: women with diabetes aged 35–59 years have the highest relative cardiovascular death risk across all age and sex groups.

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