Men and women exhibit differences in fat distribution, affecting their risk of cardiovascular disease and type 2 diabetes. Men tend to develop type 2 diabetes at lower BMIs and earlier ages than women, with abdominal fat in obese men showing higher insulin resistance than women. Evidence suggests that raised levels of free fatty acids from the breakdown of fat cells through lipolysis can contribute to inflammation and insulin resistance, with a gene playing a role in higher insulin resistance in men. Researchers have identified different levels of lipolysis, lipogenesis, and insulin sensitivity in men and women with obesity, proposing that sex hormones affect metabolic pathways in adipose tissue.

A study from the Karolinska Institutet in Sweden found that men exhibited higher levels of circulating fatty acids and insulin values than women with obesity, despite similar levels of physical activity, cardiometabolic disease, or nicotine use. Insulin sensitivity in women with obesity was found to be ten times higher compared to men, with men showing increased lipolysis rates. Differences in gene expression, including the gene encoding insulin receptor substrate 1, were also observed between men and women with obesity. These findings suggest that hormonal profiles in men and women play a role in the metabolic pathways in adipose tissue, influencing insulin resistance.

Men are known to develop type 2 diabetes at lower BMIs and younger ages than women, with a study from Australia showing that men have a higher risk of developing diabetes-related complications. These complications include cardiovascular disease, lower limb complications, kidney complications, and diabetic retinopathy, leading to the question of whether men and women should follow different treatment pathways for diabetes. Women may benefit more from weight-reducing drugs and specific GLP-1 agonists, especially considering hormonal differences in insulin sensitivity between men and women.

Researchers highlight the need for further investigation into the differences in fat distribution and behavior between men and women to develop targeted interventions for insulin resistance in men with obesity. Gender-specific considerations in therapies and interventions for type 2 diabetes are necessary, given the biological differences in fat storage, insulin sensitivity, and lipid profiles between men and women over their lifespans. To improve diabetes research, studies addressing weight reduction outcomes may need to include measurements of body fat distribution, lean mass, and intraorgan fat deposits to develop precision therapies for both men and women based on individualized responses.

The first study’s findings were drawn from a cohort predominantly of white European origin, limiting the generalizability of the results to other ethnicities and populations with a higher risk of type 2 diabetes. Diversifying participant cohorts in diabetes studies is essential to capture the unique characteristics of different ancestries and improve understanding of the disease’s impact across diverse populations. Precision therapies and interventions for type 2 diabetes should consider sex and gender differences in pathophysiology and response to treatment, focusing on factors such as body fat distribution, lean mass, and organ-specific fat deposits to target metabolic pathways in men and women effectively.

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