It’s possible that women’s HbA1c-based diabetes diagnosis thresholds are too high

Although women are more likely than men to develop diabetes mellitus later in life, the condition often results in a higher death rate in women. Because of this, scientists are now unsure if the cut-off values used to diagnose diabetes mellitus are accurate. If not, one reason for this discrepancy may be the delayed diagnosis of diabetes in women.

This theory is investigated in a recent study that was published in Diabetes Therapy by looking at the distribution of glycated hemoglobin (HbA1c) levels in men and women who are premenopausal and of similar age.

Introduction

Over 537 million adults worldwide suffer from diabetes mellitus, the majority of whom have type 2 diabetes, which can lead to illness and death from both direct and indirect complications. Compared to men of similar age, women have a higher risk of both diabetes mellitus and cardiovascular disease (CVD) in conjunction with diabetes.

When compared to other age groups or sexes, women with diabetes between the ages of 35 and 39 have the highest relative risk of cardiovascular death. Regardless of the existence of diabetes, women are also far less likely than men to receive treatment or secondary preventive measures. In addition, compared to men with the same level of risk factors, women use less medication.

When comparing diabetic women between the ages of 16 and 60 to diabetic men of the same age, the mortality risk for the former is approximately 27% higher than for the latter. Diabetes reduces a person’s lifespan by 5.3 years on average for women and 4.5 years on average for men.

Compared to men, women are typically diagnosed with diabetes mellitus later in life. Pre-diabetes, also known as non-diabetic hyperglycemia (NDH), is more prevalent in women and is linked to a higher incidence of CVD; nonetheless, the risk of death from all causes is similar for both sexes.

HbA1c levels, which have historically been used as a marker of long-term blood glucose control and the risk of diabetes, are usually used to screen for the disease. However, individual and age-specific variations result from HbA1c’s reliance on red blood cell longevity, including reduced levels in hemolytic conditions or iron deficiency anemia.

A small study with only about 200 participants who had type 1 diabetes mellitus has defined the range of normal values for HbA1c; the ratio of female to male participants was not disclosed. Nonetheless, past studies show that premenopausal women have lower HbA1c levels than men do at the same age. This could be because red blood cells have a shorter lifespan as a result of the erythrocytes lost during menstruation.

Therefore, in order to prevent the possibility of overlooking a diabetes diagnosis in premenopausal women, a particular cut-off and reference range for HbA1c are required. In an attempt to develop a new reference range and cut-off for premenopausal women, the current study looked at variations in the distribution of HbA1c in men and women. The number of new diabetes diagnoses in this category that would occur if the resulting new reference range were to be used was also estimated by the researchers.

What did the study show?

There were two cohorts in the study. In the first, more than 146,000 people were included who had a single HbA1c value between 2012 and 2019 that was at or below 50 mmol/mol. Readings from a second cohort of roughly 940,000 individuals, whose samples were examined in six labs between 2019 and 2021, were used to duplicate the distribution.

For the lack of more precise information, women 50 years of age or younger were classified as premenopausal. According to the first cohort’s results, premenopausal women’s HbA1c levels were considerably lower than those of men in the same age range. More precisely, compared to men, premenopausal women maintain an average HbA1c level of 1.6 mmol/mol.

The difference was less at 0.9 mmol/mol at or after 50 years of age, with only about 30 percent of women being diagnosed with diabetes. Compared to men under 50 years of age, only approximately 50% of women were diagnosed with diabetes at each HbA1c level.

At any given age, the mean HbA1c level in women matched that in men up to a decade prior. The data gathered from the second cohort supported these conclusions.

An undermeasurement of approximately 1.6 mmol/mol HbA1c in women may delay their diabetes mellitus diagnosis by up to 10 years.”

0.26% of women between the ages of 16 and 50 would have been diagnosed with diabetes mellitus if the new HbA1c cut-off for premenopausal women had been applied instead of the previous 48 mmol/mol.

If one were to extrapolate this to the population of England and Wales, premenopausal women would have roughly 35,000 missed diagnoses. This would cause the prevalence of diabetes in this age group to rise by an estimated 17%.

What are the implications?

The results of the HbA1c analysis of more than a million men and women in England revealed that women had significantly lower mean HbA1c levels than men under the age of 50.

Using an appropriately lower cut-off in women, the researchers estimated that over 17% of women living in England or Wales who are 50 years of age or younger would receive a new diagnosis of diabetes mellitus based on this disparity. Almost two thirds of the difference in mortality rates between men and women with diabetes mellitus in adults 50 years of age or younger could be attributed to this high percentage of missed diagnoses.

According to the study’s findings, a large number of women probably have diabetes, but they will likely receive a diagnosis later than men, which could negatively impact their CVD profile when they do. Diabetes doubles the risk of atherosclerosis and the consequent cardiovascular disease (CVD).

It might be necessary to reevaluate the HbA1c cut point for the diagnosis of diabetes mellitus in women under 50. Thus, by enabling the early detection of diabetes mellitus, a new cut-off value for HbA1c values could considerably improve the long-term health outcomes for women.