Why are men more likely to develop diabetes and develop complications despite having a lower BMI?

Patients with type 2 diabetes from the Stockholm area were recruited between 1993 and 2020 for various metabolic studies.

For this part of the study, 2,344 women and 787 men who self-reported being weight stable for three months were recruited. They were invited to come to the clinic at 8 a.m. after fasting overnight.

Data was also collected on BMI, age, physical activity, cardiometabolic disease, and smoking. The researchers administered blood tests to measure circulating levels of fatty acids and insulin in male and female participants, adjusting for BMI, physical activity, cardiometabolic disease, and smoking.

Subcutaneous fat samples were also collected from the abdomen from 259 female participants and a subset of 54 male participants.

Blood tests AdipoIRshowed that men had higher circulating levels of fatty acids and insulin than women, but only if they were obese.

These sex differences occurred regardless of level of physical activity, presence or absence of cardiometabolic disease, or nicotine use.

The researchers found that there were differences in the levels of lipolysis and adipogenesis (fat production) and the cellular sensitivity to them between obese men and women, but not between non-obese men and women.

In fact, adipose tissue from obese women has been shown to be 10 times more insulin sensitive than men, and fat cells from obese men have twice the rate of lipolysis compared to women.

Gene expression in a second group was also investigated, and the study included a group of 115 obese men and 234 women.

The researchers looked at the mRNA expressed in fat cells to see which genes were being expressed. They found that the gene encoding insulin receptor substrate 1 was IRS1 Expression was lower in men than in women.

Further analysis revealed differences in the expression of certain genes, including testosterone receptors, when comparing male and female adipose tissue.

The study authors argue that the sex differences seen are due to differences in hormonal profiles between men and women that affect metabolic pathways in adipose tissue.

Alexandra Kautsky-Wheeler, MD“We're not going to be able to do anything,” said Dr. Gregory B. Schneider, an expert in endocrinology and gender medicine at the Medical University of Vienna, who was not involved in the study. MNT that “[w]”Women have to gain more weight to develop diabetes,” meaning that women often have a higher BMI than men at the time of diagnosis, and therefore have similar insulin resistance at that point.

Previous research Men have been shown to be more likely to develop type 2 diabetes at a lower BMI than women, and some experts believe this is due to differences in fat distribution. Men also tend to develop the disease at a younger age.

Another recently published study Journal of Epidemiology and Community Health Men are at higher risk of developing complications associated with type 1 and type 2 diabetes than women, regardless of the duration of diabetes.

An analysis of an Australian-based cohort of 25,713 men and women aged 45 years and over showed that men had a 51% higher risk of cardiovascular disease, a 47% higher risk of lower limb complications, a 55% higher risk of renal complications and a 14% higher risk of diabetic retinopathy compared to women.

Given gender differences in terms of insulin resistance and risk of serious diabetes-related complications, the question arises: “Should men and women follow different treatment pathways?”

“Weight loss medications are desirable for all people with type 2 diabetes, but especially for women,” Kautsky-Wiler said. MNT Several different GLP-1 agonists was More effective in women than men.

“During puberty, women are more insulin resistant but thereafter, until menopause, they have better insulin sensitivity, insulin responsiveness, lipid profile (lower LDL cholesterol), lower blood pressure and better fat stores (energy reserves for potential pregnancy) but after menopause, women lose their biological advantage and develop an androgenic phenotype,” she elaborated.

The authors of the first study say their findings suggest that insulin resistance in obese men may be specifically targeted with drug and lifestyle interventions to prevent type 2 diabetes, but argue that the findings need to be confirmed by future research.

The reasons for the differences in fat distribution and behavior require further investigation, Kautsky-Wiler said.

“Sex and gender differences in treatments and interventions need to be explored. Most studies are underpowered to provide valuable insights, with only 30% of studies being female. [of the cohort]” she pointed out.

“However, women are typically far more prevalent (70%) in obesity studies, and therefore around 50% of randomized controlled trials in obesity are female,” she further suggested, “so there is an opportunity to explore sex differences in pathophysiology and response to treatment.”

To improve diabetes research, Kautsky-Wiler argued:

“[I]As a result, it becomes necessary to measure more than just weight loss: changes in body fat distribution and lean mass (muscle!) need to be investigated, and changes in intra-organ fat deposition need to be studied. [fat deposits inside organs, such as the] “The pancreas, the heart, etc. Then we can discover new targets and begin to provide true precision medicine for men and women.”

About 95% of the original study cohort was white European, so the findings cannot be extrapolated to people of other ancestries, even though people of African and Asian descent are more likely to develop type 2 diabetes. Therefore, diversifying participant cohorts in diabetes studies would be another step forward.