Men with type 2 diabetes and obesity exhibit higher levels of insulin resistance in their adipose tissue than women, according to researchers from the Karolinska Institutet in Stockholm, Sweden.

The study, led by Dr. Daniel Andersson, found that the increased insulin resistance in men is due to a less effective inhibition of fat cell lipolysis, the process by which fat is metabolized. This inefficiency results in higher levels of free fatty acids, which contribute to inflammation and insulin resistance. The research also identified a gene that may play a role in this disparity.

Published in the International Journal of Obesity in March 2024 and presented at the European Congress on Obesity in Venice, Italy, the study involved 3,131 participants from the Stockholm area, recruited between 1993 and 2020. The study included 2,344 women and 787 men who reported stable weight for three months. Participants attended a clinic after overnight fasting, where data on BMI, age, physical activity, cardiometabolic disease, and tobacco use was collected.

Blood tests revealed that men with obesity had higher levels of circulating fatty acids and insulin compared to women. These differences were independent of physical activity, cardiometabolic disease, or tobacco use. Furthermore, subcutaneous fat samples from a subset of participants showed that women with obesity had ten times higher insulin sensitivity than men, whose fat cells exhibited twice the rate of lipolysis.

The researchers also examined the genetic expression in fat cells and found that the gene encoding insulin receptor substrate 1 (IRS1) was less expressed in men than in women. Differences in the expression of certain genes, including testosterone receptors, were also noted.

Dr. Alexandra Kautzky-Willer from the Medical University of Vienna, who was not involved in the study, highlighted that women generally need to gain more weight to develop diabetes, resulting in a higher BMI at diagnosis and similar insulin resistance to men.

Previous research has shown that men are more likely to develop type 2 diabetes at lower BMIs and younger ages than women. Additionally, men face a higher risk of diabetes-related complications, such as cardiovascular disease, lower limb issues, kidney complications, and diabetic retinopathy.

Given these sex differences, there is a question of whether men and women should follow different treatment pathways for diabetes. Dr. Kautzky-Willer suggests that weight-reducing drugs are preferred for all patients but may be particularly effective for women. She noted that some GLP-1 agonists are more effective in women than men.

The study's authors propose that targeting insulin resistance in men with obesity through pharmaceutical and lifestyle interventions could help prevent type 2 diabetes. However, they stress the need for prospective studies to confirm their findings.

Dr. Kautzky-Willer emphasized the importance of investigating sex and gender differences in therapies and interventions, noting that most studies are underpowered to provide valuable insights, with women often comprising only 30% of study cohorts. However, in obesity studies, women often make up 70% of participants, offering a unique opportunity to explore these differences.

The findings highlight the need for a more personalized approach to diabetes treatment, taking into account the distinct physiological responses of men and women.