A brand new study has suggested that A1C measurements could also be inaccurate in young women, because of increased red blood cell turnover triggered by blood loss during menstruation. If true, it could mean that many ladies with diabetes have been diagnosed late and systematically undertreated. The lead researcher believes that this may occasionally explain why women with diabetes, especially young women, appear to have higher relative macrovascular risks than men.
The study, which has been published within the medical journal Diabetes Therapy, is the work of a team led by Adrian Heald, MD, an endocrinologist at the UK’s Salford Royal Hospital. Dr. Heald believes that diabetes authorities should consider changing the A1C cutoffs used to assist diagnose diabetes to account for this factor.
Though Heald’s study only considers type 2 diabetes, it is feasible that girls with type 1 diabetes are similarly affected.
The Problem: Women with Diabetes Have Higher Relative Rates of Mortality and Complications
Heald’s theory begins with the statement that girls with type 2 diabetes usually tend to suffer severe negative outcomes attributable to diabetes. In a paper published earlier this 12 months (PDF), Heald and collaborators found that girls within the Salford area, especially young women, had the next relative mortality rate, due mostly to an enhanced risk of heart problems.
It is a global pattern. A 2007 meta-analysis considered 37 studies from internationally, and concluded that “the relative risk for fatal coronary heart disease related to diabetes is 50 percent higher in women than it’s in men.” And a 2017 editorial in The Lancet noted that girls with type 2 diabetes “have as much as 27 percent higher excess risk of stroke and 44 percent higher excess risk of coronary heart disease.” There may be, the editorial states, “ever-increasing evidence that diabetes adversely affects women greater than men.”
Despite the differences in outcomes, women within the Salford area had higher glycemic control, as measured by A1C, and were diagnosed with diabetes at later ages. Their risk aspects seemed superficially lower, and so they were less regularly prescribed cardioprotective drugs similar to beta-blockers, SGLT2 inhibitors, or statins.
This end result disparity could have multiple possible causes. Women could have a biological tendency to experience worse outcomes from diabetes than men. However it is arguably more probable that the gap is said to the quality of care that girls receive. The Lancet editorial concludes that “sex differences in psychosocial aspects, health-seeking behavior, and provision of health care are probably more essential.”
The Possible Cause: Menstruation and A1C
The relative risks to women with type 2 diabetes appear to peak before the top of the menopausal transition. Heald writes that “women with diabetes aged 35–59 years have the very best relative cardiovascular death risk across all age and sex groups.”
A 2021 study found that girls under the age of fifty have much lower A1C measurements than men of the identical age — but that after the age of fifty, the ladies’s A1Cs escalate rapidly. All adults are inclined to have rising A1Cs as they age, but after the age of fifty, women within the sample experienced a way more dramatic rise.
In his recent paper, Heald offers a possible explanation. It is feasible that premenopausal women could also be receiving lesser care because their A1Cs have been systematically misinterpreted, a consequence of blood loss throughout the menstrual cycle:
“This may increasingly be because of menstruation and hence shorter erythrocyte [red blood cell] survival which leads to shorter exposure of haemoglobin to glucose compared with individuals who don’t menstruate.”
Here’s how it really works: The A1C test is an indirect approach to measure average blood sugar levels over the previous couple of months. Sugar within the bloodstream binds to hemoglobin molecules in red blood cells after they’re created. Red blood cells are inclined to live for about three or 4 months, and so measuring the sugar sure to hemoglobin gives an estimate of recent blood sugar history. Nevertheless, any lack of blood requires the body to create more recent red blood cells. The more red blood cell turnover, the less time recent cells are exposed to sugar, which leads to misleadingly low A1C measurements.
For now, this is just a hypothesis. Chatting with Diabetes Each day, Heald stated that the phenomenon has “not been checked out intimately before.” He’s hopeful that his speculation will spur more research: “It definitely must be checked out!”
There may be also some corroborating evidence: we all know that donating blood may end up in a falsely lowered A1C. A 2017 study found that barely greater than half of adults, each with and without diabetes, had a major reduction in A1C following blood donation. Amongst participants with type 2 diabetes, the most important A1C drop was about -12.0 percent. On the American A1C scale, that would represent a fall from an A1C of 8.0 percent all the best way right down to 7.0 percent. That’s a striking result, though it’s essential to notice that blood donation often removes much more liquid (500 mL) abruptly than a typical menstrual cycle does (60 mL) over a period of days.
The Negative Impact of Misleading A1C Results
If menstruation truly does have this misleading effect, it implies that the medical system is systematically underestimating the size of hyperglycemia in an enormous percentage of individuals.
A1C will not be the one measurement used to diagnose diabetes, and a few experts imagine that A1C results should at all times be confirmed with alternative criteria. Women with polycystic ovary syndrome (PCOS), which is extremely common in type 2 diabetes, are advisable to make use of an oral glucose tolerance test (OGTT) fairly than A1C. But A1C stays popular amongst clinicians, partially because it could actually be administered quickly and with none special preparations.
When the diagnosis of diabetes is delayed, it implies that patients are slower to receive medication and lifestyle counseling. It means they’re slower to be prescribed statins, anti-hypertensive drugs, or other therapies commonly advisable to individuals with diabetes. And consequently, it could explain among the end result gap between men and women.
To place it simply, men under the age of fifty is perhaps receiving appropriate medical care more quickly than women of the identical age.
Imprecise A1C results, in fact, may only be one piece of the puzzle. Heald believes that diabetes authorities should consider lowering the diagnostic threshold for type 2 diabetes for premenopausal women with a view to speed up their treatment:
“Timely diagnosis of type 2 diabetes and initiation of preventative treatment has the potential to enhance cardiovascular risk profile over the lifetime and facilitate longer life quality and expectancy in women. Our findings provide evidence that the A1C threshold for this group needs to be re-evaluated.”
A1C isn’t only used for the diagnosis of diabetes, but additionally for its management. If Heald is correct, it could eventually result in different glycemic targets for young women with established diabetes:
“Should there be a real difference in A1C between men and ladies as much as the age of fifty … that might mean barely lower A1C targets for monitoring in addition to diagnosis.”
Could A1C Be Misleading for Women with Type 1 Diabetes, Too?
Heald’s article focuses on type 2 diabetes, but he speculates that “the identical principle applies” to women with type 1 diabetes.
There may be also an identical pattern of end result inequities in type 1 diabetes. Diagnosis often occurs later for girls and girls, and the disease is more dangerous, too:
This gap can’t be entirely the results of menstruation, because a few of these differences exist before puberty. And we all know that hormonal changes bring their very own serious management challenges which proceed through the menopausal transition.
More Study Needed
Heald stressed that his work is just preliminary — “there must be validation of our findings in other population samples, ideally with detailed phenotype data in addition to biochemistry data.” In the intervening time, he doesn’t advise women with diabetes to vary anything about their management. He’s hopeful that his work will spur other researchers and diabetes authorities to contemplate these issues seriously.