Unraveling the Mystery: Why Type 2 Diabetes Diagnosis Differs Between Women and Men

Statistically, type 2 diabetes appears more prevalent in men, with global figures indicating approximately 18 million more men living with the condition worldwide. However, this statistic presents only a partial view of the complex landscape of diabetes. A deeper examination reveals a significant disparity in how the disease manifests, is diagnosed, and progresses in women compared to men. When women receive a type 2 diabetes diagnosis, it is often at a later age, frequently accompanied by a higher body fat mass. More concerningly, women diagnosed with type 2 diabetes face a higher likelihood of mortality from diabetes-related complications, particularly cardiovascular disease. This raises critical questions about potential underdiagnosis in women, suggesting that a substantial number of cases might be missed or delayed, contributing to the observed disparities in outcomes.

Addressing this critical health disparity requires a comprehensive understanding of the underlying factors. Researchers are actively investigating the intricate biological and social differences that contribute to these later diagnoses and poorer health trajectories in women. Their findings suggest that current diagnostic approaches may need re-evaluation to identify at-risk women earlier, a crucial step that could significantly enhance the effectiveness of treatments and lifestyle interventions.

Biological Factors Influencing Diabetes in Women

Several potential reasons contribute to the observed differences in type 2 diabetes diagnosis patterns between men and women. While many risk factors for the condition are universal, their timing and presentation can vary significantly based on sex. The disease itself may manifest differently in women, potentially leading existing diagnostic tools to overlook early signs. According to Michael Leutner, a professor in endocrinology and metabolism at the Medical University of Vienna, the selective use of certain diagnostic tests over others is a "major reason for underdiagnosis of diabetes in women."

Fundamental biological differences between the sexes, particularly the influence of hormones, play a crucial role in type 2 diabetes development and progression. Major hormonal shifts throughout a woman's life, such as those occurring during pregnancy and menopause, can profoundly impact how her body regulates blood sugar levels.

The Impact of Hormonal Shifts Across a Woman's Lifespan

Life events marked by significant hormonal changes are particularly relevant to a woman's type 2 diabetes risk:

• Gestational Diabetes: Pregnancy-related gestational diabetes is a powerful predictor of future type 2 diabetes. Judith Regensteiner, director of the Ludeman Family Center for Women’s Health Research at the University of Colorado Anschutz Medical Campus, describes it as "one of the most powerful harbingers of things to come." Indeed, a diagnosis of gestational diabetes is recognized as the single biggest risk factor for type 2 diabetes in women. Some studies indicate that women who experience gestational diabetes are up to eight times more likely to develop type 2 diabetes later in life compared to those who do not. This highlights the importance of post-pregnancy screening and early intervention for women with a history of gestational diabetes.
• Menopause: The transition through menopause brings about significant hormonal changes, most notably a decline in estrogen levels. Estrogen is believed to play a protective role in blood sugar regulation. It helps cells respond more effectively to insulin and protects the pancreatic beta cells responsible for producing insulin from damage. As estrogen levels fall during menopause, the body's ability to manage blood sugar declines, contributing to an increased risk of developing type 2 diabetes during midlife.

Fat Distribution and Insulin Resistance

How and where fat is stored in the body is a critical risk factor for type 2 diabetes, but the metabolic impact varies depending on the type of fat and its location. Peter Goulden, associate professor at the Icahn School of Medicine at Mount Sinai, explains that visceral fat, the deep belly fat surrounding internal organs, is particularly harmful. Visceral fat releases free fatty acids that increase insulin resistance. Insulin acts like a key, unlocking cells to allow glucose to enter and be used for energy. With insulin resistance, cells become less responsive to this key, causing glucose to accumulate in the bloodstream.

Before menopause, women tend to store fat subcutaneously around the hips and thighs, which is considered metabolically less harmful than visceral fat. However, the hormonal shifts during menopause, particularly the decrease in estrogen, lead to a redistribution of fat, with more fat being stored viscerally. This post-menopausal accumulation of deep belly fat poses a greater risk for women than for men. A 2019 study found that each kilogram of visceral fat increases a woman's risk of developing type 2 diabetes by approximately seven times, a risk roughly triple that observed in men. This difference in fat storage patterns, influenced by hormonal status, helps explain why women are often diagnosed at an older age, after menopause.

The accumulation of visceral fat can occur even without a person being classified as obese based on traditional measures like body mass index (BMI). This limitation of BMI means that it can sometimes miss early diabetes risks, particularly in women. One study indicated that while BMI was a stronger predictor of type 2 diabetes in men, measurements related to waist size were more strongly associated with risk in women. Recognizing this, the American Diabetes Association (ADA) updated its guidelines on diabetes management last year to recommend that measurements such as waist circumference be considered alongside BMI when assessing obesity and metabolic risk. This shift acknowledges the importance of fat distribution, not just overall weight, particularly for women.

Challenges in Diagnosis: Are Current Tools Missing Women?

Beyond the biological differences in disease progression, there are growing concerns that standard diagnostic tools may not be as effective at identifying the early signs of type 2 diabetes in women, especially younger women, compared to men.

The HbA1c Test: A Potential Blind Spot?

The hemoglobin A1c (HbA1c) blood test is a widely used diagnostic tool due to its convenience, as it does not require fasting. It provides an estimate of average blood glucose levels over the preceding two to three months by measuring the percentage of hemoglobin in red blood cells that is coated with sugar. However, recent research suggests that this test might not be as sensitive in detecting diabetes risk in some younger women.

Studies have shown that women typically have lower levels of HbA1c than men of the same age before menopause. Researchers in Taiwan have therefore suggested that "the HbA1c cut-off point for the diagnosis of diabetes should vary by age and gender." A 2023 study from the UK, which analyzed data from over a million individuals, similarly found that women had slightly lower average HbA1c levels than men. The study estimated that if the diagnostic threshold for HbA1c were slightly reduced for women, an additional 35,000 women in England and Wales could potentially be diagnosed with diabetes or prediabetes.

Despite this evidence, current diagnostic cutoffs for HbA1c remain the same for both men and women in many regions, including the UK, as highlighted by Diabetes UK guidelines. Experts like Peter Goulden argue that there isn't yet sufficient data to support changing these cutoffs. Michael Leutner agrees, stating, "We need more prospective clinical studies to investigate it."

Advocating for the Oral Glucose Tolerance Test (OGTT)

Instead of solely relying on adjusting HbA1c thresholds, some experts, including Leutner, advocate for greater utilization of the oral glucose tolerance test (OGTT). The OGTT is considered a more sensitive tool for detecting impaired glucose tolerance, a precursor to type 2 diabetes, particularly in its early stages. This test involves fasting, followed by measuring blood glucose levels before and at intervals after consuming a standardized sugary drink.

Leutner points out that men are more likely to have elevated fasting glucose levels or high random glucose levels caught during routine blood work, which the HbA1c test is effective at identifying. However, "Females on the other hand more often have impaired glucose tolerance, which can only be measured with the more complex OGTT," he explains. This suggests that a diagnostic strategy that relies heavily on HbA1c might systematically miss cases of impaired glucose tolerance in women, leading to delayed diagnoses.

Social Factors and Healthcare Disparities

Beyond the biological and diagnostic challenges, social factors and systemic issues within healthcare also contribute to the different outcomes observed between women and men with type 2 diabetes.

Patient Perception and Dismissal of Symptoms

Judith Regensteiner notes that, in her experience, some women may not fully appreciate the seriousness of a diabetes diagnosis. She recounts hearing patients say things like, "I've got a little bit of diabetes." This casual attitude can lead to a delay in seeking care or adhering to treatment plans. "It's not a little bit. It's a serious disease," Regensteiner emphasizes. This potential tendency to downplay symptoms or the diagnosis itself could contribute to later engagement with healthcare and management strategies.

Clinician Bias and Treatment Disparities

Clinicians may also underestimate the risks associated with type 2 diabetes in women. Research indicates that women with type 2 diabetes are less likely to be prescribed certain cardioprotective medications compared to men, even though diabetes significantly increases their risk of fatal heart disease. While men have a higher baseline risk of heart disease, type 2 diabetes disproportionately increases this risk for women, tipping the balance such that fatal heart disease associated with diabetes is 50 percent more common in women than men, according to a study published in the BMJ. This disparity in prescribing patterns suggests a potential bias or lack of awareness regarding the heightened cardiovascular risk faced by women with diabetes.

Historical Exclusion from Research

A significant historical factor contributing to our incomplete understanding of sex differences in diseases like type 2 diabetes is the past exclusion or underrepresentation of women in clinical research studies. For decades, many early clinical trials that established risk guidelines and treatment protocols for various conditions, including diabetes, primarily included male participants. When women were included, it was often in smaller numbers, and their data were frequently pooled with that of men rather than being analyzed separately.

Regensteiner highlights that this historical practice has detrimental effects on both sexes because "the results are muddied." Without analyzing data based on sex, researchers miss crucial differences in disease presentation, progression, and response to treatment. "There are sex differences, and ignoring them will not help," she states. This lack of sex-specific data has likely contributed to diagnostic criteria and treatment guidelines that are less optimized for women, potentially leading to delayed diagnoses and less effective management strategies.

Consequences of Delayed Diagnosis and Worse Outcomes

A delayed diagnosis of type 2 diabetes in women has significant health consequences. The longer the condition goes undetected and untreated, the more time high blood sugar levels have to damage organs and tissues throughout the body. This damage contributes to the higher rates of complications seen in women, particularly cardiovascular disease.

As mentioned, while men are generally more prone to heart disease, diabetes erases this advantage, making heart disease a particularly deadly complication for women with the condition. The fact that heart disease may also go undetected for longer in women, as noted by Regensteiner, further exacerbates this risk. Delayed diagnosis means delayed initiation of critical interventions, including lifestyle modifications, glucose-lowering medications, and cardioprotective therapies, allowing complications to advance further before they are addressed.

Other potential complications of uncontrolled type 2 diabetes, such as kidney disease, nerve damage (neuropathy), eye damage (retinopathy), and foot problems, can also become more severe when diagnosis and management are delayed. The cumulative effect of these complications can significantly reduce a woman's quality of life and lifespan.

Moving Towards More Equitable Diabetes Care

Recognizing and addressing the disparities in type 2 diabetes diagnosis and outcomes for women is crucial for achieving more equitable healthcare. The research discussed points towards several areas for improvement:

1. Enhanced Awareness: Both patients and healthcare providers need increased awareness of how type 2 diabetes can present differently in women and the specific risk factors they face, such as a history of gestational diabetes and the impact of menopause. Women should be encouraged to take potential symptoms seriously and discuss their risk factors openly with their doctors.
2. Improved Diagnostic Strategies: Relying solely on HbA1c may not be sufficient for all women, particularly younger ones. Increased use of the oral glucose tolerance test (OGTT) could help identify impaired glucose tolerance earlier. Furthermore, incorporating measurements like waist circumference alongside BMI provides a more complete picture of metabolic risk related to fat distribution.
3. Tailored Screening Recommendations: Given the hormonal influences and later onset often seen in women, a case can be made for considering sex-specific screening guidelines or adjusting screening frequency based on life stages like menopause. As Goulden suggests, "really there should be lifelong screening," but perhaps with different emphases at different ages.
4. Addressing Treatment Disparities: Healthcare providers must be mindful of the heightened cardiovascular risk in women with type 2 diabetes and ensure they receive appropriate cardioprotective medications and management strategies at the same rates as men.
5. Promoting Sex-Specific Research: Future clinical studies must actively recruit diverse populations, including sufficient numbers of women, and analyze data separately by sex to identify and understand sex-specific differences in diabetes development, progression, and treatment response. This will lead to more accurate diagnostic criteria and more effective, personalized treatment plans.

The journey towards understanding and mitigating the disparities in type 2 diabetes care for women is ongoing. By acknowledging the complex interplay of biological vulnerabilities, diagnostic limitations, and social factors, the medical community can work towards earlier detection, more effective interventions, and ultimately, better health outcomes for all women living with or at risk of type 2 diabetes.