Diabetes is not a gender-neutral disease and should no longer be managed as though it were, according to Susanne Reger-Tan, MD, a professor and director of the Department of Diabetology and Endocrinology at the Heart and Diabetes Center North Rhine-Westphalia in Bad Oeynhausen, Germany.

During an online press conference organized by the Association of Diabetes Counseling and Education Professionals in Germany, Reger-Tan said that hormonal changes across a woman’s life substantially influence glucose metabolism, insulin requirements, and cardiovascular (CV) risk. However, these differences remain underrecognized in clinical practice.

“Diabetes is not a gender-neutral disease and therefore should no longer be treated as such,” said Reger-Tan.

“Medicine understands women less well than men and treats them differently,” said Reger-Tan.

She attributed this disparity, in part, to the gender data gap, noting that women remain underrepresented in clinical research. Hormones directly influence insulin action, beta cell function, fat distribution, and CV risk, whereas glucose metabolism changes throughout a woman’s life. However, the roles of estrogen and progesterone in glucose regulation remain unclear.

According to Reger-Tan, this knowledge gap contributes to a broader gender-health gap in which women receive different and, in some areas, less effective care.

“Both gaps can now be demonstrated with data, and both are preventable,” said Reger-Tan.

Early Warning Signs

Using polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), as an example, Reger-Tan illustrated the close relationship between endocrine function, metabolism, and CV risk.

PMOS affects approximately 1 in 8 women. Insulin resistance accompanied by compensatory hyperinsulinemia occurs in about three quarters of women with normal weight and nearly all women with overweight who have the condition.

The syndrome contributes to androgen excess and ovulatory dysfunction, while substantially increasing cardiometabolic risk. Compared with women without PMOS, affected women are 10 times more likely to develop obstructive sleep apnea, type 2 diabetes is four times more common, gestational diabetes is twice as common, and women with PMOS are more likely to have metabolic dysfunction-associated steatotic liver disease, regardless of BMI and CV disease, with CV events occurring even before menopause. Despite these risks, up to 70% of affected women remain undiagnosed.

Gestational diabetes is another important sex-specific warning sign. It increases the subsequent risk for type 2 diabetes sevenfold to tenfold and doubles the CV risk. According to Reger-Tan, gestational diabetes and PMOS share common pathophysiologic mechanisms and genetic susceptibility, making both conditions important opportunities for early prevention.

Hormonal Fluctuations Across the Menstrual Cycle

Even a normal menstrual cycle produces predictable changes in insulin sensitivity.

During the follicular phase, estrogen improves insulin sensitivity. During the luteal phase, progesterone increases insulin resistance, resulting in insulin requirements that may increase by as much as 15%.

These changes can be readily detected using continuous glucose monitoring. However, current automated insulin delivery systems do not account for hormonal fluctuations throughout the menstrual cycle. Consequently, many women must adjust their insulin doses manually, often without adequate clinical guidance.

To address this gap, the TIMES study was launched by the Diabetes Center Berne. The multinational study investigated 350 women with type 1 diabetes (T1D) in Switzerland, Denmark, the UK, the US, and Germany tracking over six menstrual cycles to identify changes in insulin sensitivity and insulin requirements. The goal is to develop menstrual cycle-adapted insulin dosing algorithms.

Menopause Brings New Challenges

These predictable hormonal patterns disappear during menopause.

Declining estrogen levels increase insulin resistance, visceral adiposity, and CV risk. However, unlike the menstrual cycle, fluctuations in estrogen and progesterone levels become unpredictable, resulting in greater glycemic variability.

In a recent Dutch study of 159 women with T1D, approximately two-thirds reported greater glucose instability after menopause. Participants had a mean age of 55 years, had lived with diabetes for approximately 30 years, and had experienced menopause at a mean age of approximately 50 years.

Overall, 67.4% of the participants reported moderate-to-severe changes in glucose regulation after menopause. Elevated glucose levels were reported to be 41.9%, lower glucose levels by 19.6%, and 38.5% reported no change in blood glucose levels. More than half (approximately 55 %) reported greater glucose variability, 61.6% experienced more hyperglycemic episodes, and 38.5% experienced more hypoglycemic episodes. An increase in the severity of menopausal symptoms was associated with a greater likelihood of changes in blood glucose levels.

Reger-Tan also cautioned that hot flashes, sweating, and palpitations may mimic hypoglycemia.

“Anyone who mistakes hypoglycemia for a hot flash will not treat it, and that can be dangerous. When in doubt, check the blood glucose level first and always treat hypoglycemia first,” said Reger-Tan.

Although research is beginning to address the effects of the menstrual cycle and pregnancy in women with T1D, menopause remains largely understudied. Reger-Tan noted that few studies are available, menopause specific guideline recommendations are lacking, and evidence supporting menopausal hormone therapy remains limited.

Persistent Gender Gaps in Diabetes Care

Reger-Tan and colleagues also examined whether treatment differences contribute to disparities in clinical outcomes.

Analyzing data from nearly 20,000 individuals with T2D and established CV or kidney disease, the researchers found that women were approximately one-third less likely than men to receive organ-protective treatment with SGLT2 inhibitors or GLP-1 receptor agonists.

The researchers also evaluated a predictive treatment model derived from more than 200,000 treatment courses. Selecting therapy according to the model, which incorporates sex among other patient characteristics, reduced the risk for treatment failure by 38% and lowered the risk for cardiorenal complications.

Reger-Tan concluded that gender sensitive diabetology is precision medicine, emphasizing that treatment should account for gender, life stage, and individual risk factors rather than applying a uniform approach to all patients.

“Gender sensitive diabetes care is not a special case. It is precision medicine,” Reger-Tan concluded.

To achieve this, she emphasized that women must be better represented in clinical research, gender-specific risk markers such as PMOS and gestational diabetes should be recognized earlier, and organ-protective therapies should be prescribed equitably whenever indicated.

This story was translated from Medscape’s German edition.