Men are at higher risk for diabetes-related complications than women. Studies have shown that men with diabetes have a higher risk of cardiovascular disease, lower extremity and kidney complications, and diabetic retinopathy. There was no significant effect of diabetes duration on gender differences. Over a 10-year period, 44% of men experienced cardiovascular complications compared to 31% of women. These findings underscore the need for targeted monitoring and prevention strategies from the time of diabetes diagnosis.
A study published in the Journal of Epidemiology & Community Health analyzed gender differences in the incidence of microvascular and macrovascular complications of diabetes. The study included 25,713 people with diabetes, aged 45 and older. Men were found to have a higher risk of cardiovascular disease, lower extremity and kidney complications, and diabetic retinopathy compared to women. The results underscore the need for monitoring and strategies to prevent complications from the time of diabetes diagnosis.
Men and women have different patterns of body fat distribution, which significantly affects their risk profile for cardiovascular disease and type 2 diabetes. In general, men tend to develop type 2 diabetes earlier and at a lower BMI compared to women.
Researchers at the Karolinska Institute in Stockholm, Sweden, have found that abdominal fat in obese men with type 2 diabetes exhibits higher insulin resistance and other levels of gene expression compared to women. This increased insulin resistance is attributed to less effective inhibition of fat cell lipolysis, the process by which fat cells break down stored fat.
In addition, research from Australia indicates that men are at higher risk for complications associated with both type 1 and type 2 diabetes compared to women.
In conclusion, men with type 2 diabetes and obesity show higher levels of insulin resistance in adipose tissue than women. This gender difference is associated with inefficiencies in inhibiting fat cell lipolysis, underscoring the importance of incorporating gender-specific approaches in the management and treatment of diabetes.
Sex differences in fat production and metabolism
The study recruited people with type 2 diabetes from the Stockholm area between 1993 and 2020 to conduct a series of metabolic studies.
This part of the study recruited 2,344 women and 787 men who self-reported stable weight for 3 months. They were invited to the clinic at 8:00 am, after an overnight fast.
Data were also collected on their BMI, age, physical activity, cardiometabolic diseases and tobacco use. The researchers conducted a blood test that measured circulating levels of fatty acids and insulin in men and women, adjusting the results for BMI, physical activity, cardiometabolic diseases and tobacco use.
A subgroup of 259 women and 54 men also had subcutaneous fat samples taken from the abdominal area.
The blood test, called Adipo-IR, showed that men had higher circulating fatty acid levels and insulin values than women, but only if they were obese.
These gender differences occurred regardless of physical activity level, the presence of cardiometabolic diseases or nicotine use.
The researchers found differences in the levels of lipolysis and lipogenesis (fat production) and the sensitivity of cells to them between men and women with obesity, but not in people without obesity.
In fact, the adipose tissue of women with obesity showed 10 times greater insulin sensitivity than that of men. Fat cells taken from men with obesity showed twice the rate of lipolysis than in women.
A second group gene expression study was also conducted, which included 115 men and 234 women with obesity.
The researchers examined mRNA expressed in fat cells to determine which genes are expressed. They found that the gene encoding insulin receptor substrate 1 (IRS1) was less expressed in men than in women.
Further analysis showed that there are differences in the expression of certain genes, including testosterone receptors in male adipose tissue compared to adipose tissue taken from women.
The study authors suggest that the observed gender differences are due to different hormonal profiles of men and women, which affect metabolic pathways in adipose tissue.
Dr. Alexandra Kautzky-Willer of the Medical University of Vienna, a specialist in endocrinology and gender medicine who was not involved in the study, said that “we know that women need to gain more weight to develop diabetes,” meaning that they often have a higher BMI than men at the time of diagnosis, and therefore show similar insulin resistance to men at that point.
Men are at higher risk of diabetes-related complications
Previous studies have shown that men are more likely to develop type 2 diabetes at a lower BMI than women, and some experts believe this is related to different fat distribution. Men are also more likely to develop the disease at a younger age.
Another study, recently published in the Journal of Epidemiological Community Health, showed that men are more likely to develop complications associated with type 1 and type 2 diabetes than women, regardless of the duration of the disease.
An analysis of a cohort of 25,713 men and women over the age of 45 from Australia found that men were 51% more likely to have cardiovascular disease compared to women, 47% more likely to have lower extremity complications, 55% more likely to have kidney complications and 14% more likely to have diabetic retinopathy.
Should men and women use different diabetes treatments?
If there are gender differences in insulin resistance and the risk of serious diabetes-related complications, the question arises: should men and women also follow different treatment pathways?
“Weight-reduction drugs are preferred for all patients with type 2 diabetes, but especially for women,” Kautzky-Willer said. She explained that some different GLP-1s were more effective in women than in men.
“During puberty, women are more insulin resistant, but later they are more insulin sensitive than men until menopause; they have a better insulin response, a better lipid profile (lower LDL cholesterol) and lower blood pressure. They have better fat storage (energy reserve for possible pregnancies); however, after menopause, women lose their biological advantages and develop an androgen phenotype,” she detailed.
The authors of the first study suggest that their results indicate that insulin resistance in obese men could be specifically targeted with pharmaceutical and lifestyle interventions to prevent type 2 diabetes, but their findings need to be supported by prospective studies.
Studying sex differences in diabetes: Directions for future research
Kautzky-Willer said the reasons for the differences in fat distribution and behavior should be further investigated.
“We need to study gender and sex differences in therapies and interventions. Most studies are not powerful enough to give worthwhile conclusions, and in most studies women make up only 30% [kohorty],” she noted.
“However, obesity studies tend to have significantly more women (70%), and thus even in some randomized controlled obesity studies we have about 50% women,” she further suggested. “So we have an opportunity to study gender differences in pathophysiology and response to treatment.”
About 95% of the cohort of the first study was from the white European population, so it is not possible to extrapolate the results to people of different backgrounds, even though people of African and Asian descent are more likely to develop type 2 diabetes. The next step forward should therefore also be to diversify the cohorts of participants in diabetes studies.
The article can be read here.
