Why do obese men have higher insulin resistance?

VENICE, Italy — New data suggests that the reason type 2 diabetes is more common in obese men than in women may be due to differences in how adipose tissue responds to insulin. Ta.

A research team led by endocrinologist Daniel P. Anderson, MD, of Karolinska University Hospital Haddinge in Stockholm, Sweden, found that men have higher levels of insulin resistance in adipose tissue. They also found that adipocytes isolated from men with a body mass index (BMI) ≥30 require 10 times higher concentrations of insulin to block the breakdown of triglycerides into free fatty acids and glycerol, and that this blocking mechanism is also effective. It was also revealed that the more men than women.

“We believe that men [compared with women] “People living with obesity had increased fat insulin resistance and higher levels of free fatty acids in their blood,” Anderson said. Medscape Medical Newsadded that this is primarily related to insulin's lower ability to block the breakdown of triglycerides in adipose tissue in men, rather than sex differences in storage capacity.

“These findings may be part of the explanation for why type 2 diabetes is more common in men than women,” he added.

Anderson presented the findings at this year's conference. European Congress on Obesity (ECO) 2024.The survey results have also been revealed published inside International Journal of Obesity.

Role of insulin in storage and release of abdominal subcutaneous fat

Insulin plays an important role in both stimulating lipid storage (conversion of circulating free fatty acids to triglycerides within adipocytes) and inhibiting lipid release (degradation of circulating triglycerides to free fatty acids) will be fulfilled.

“With insulin resistance, there is less inhibition of breakdown and more free fatty acids are released into the circulation,” Anderson explained. “At the same time, storage activity is reduced, so more free fatty acids remain in circulation.”

The body's organs then become chronically exposed to excess fat cell-derived fatty acids, leading to decreased muscle glucose uptake, increased liver production of sugar, and decreased insulin secretion by the pancreas. This causes further hyperglycemia, further reduction in glucose uptake, and increased triglyceride breakdown in fat cells, which Anderson described as a “vicious cycle.”

The main differences between men and women revealed

To clarify the functional differences between men and women, researchers measured the adipose insulin resistance index (AdipolR) in the abdominal subcutaneous fat of 2,344 women and 787 men (mean age 44 years, mean BMI 35). did.

We found that men have higher AdipoIR values ​​than women (P < .0001), but only for people with a BMI ≥ 30 (i.e. obese). This pattern remained the same regardless of whether participants were physically active, had a cardiometabolic disease, or used nicotine.

Andersson and colleagues then isolated adipocytes from biopsies of subgroups of 259 obese women and 54 men and compared the effects of insulin on adipocytes in these different groups.

“We found that 10 times higher concentrations of insulin were needed to block the breakdown of triglycerides into fatty acids compared to women, and that the inhibition was less effective in men,” he said. said.

Weigh the possible impacts

“While we know that type 2 diabetes is associated with adipose tissue, it is not entirely clear how the disease develops,” Anderson explained. “Removing adipose tissue alone does not improve insulin sensitivity. Therefore, this is related to the health of the fat cells, and improving blood sugar control through medication, diet, and other methods can only improve insulin sensitivity.” We think we need to change their function,” or bariatric surgery to fine-tune lipolysis and adipogenesis in these cells. ”

Dr. Gijs Goossens, Professor of Obesity Cardiometabolic Physiology at Maastricht University Medical Center+ in Maastricht, Netherlands, commented on the study results and reflected on the role of body fat on insulin.

“It is well established that premenopausal obese women are relatively protected from cardiometabolic complications compared to men of the same age and BMI, and this is at least partially due to body fat “This is due to a more favorable body fat distribution pattern in both the skeletal muscles and the liver,” he said. Medscape Medical News.

“The finding that insulin resistance in abdominal subcutaneous adipose tissue is more pronounced in obese men than in women provides further evidence that there are significant sex differences in the pathogenesis of obesity-related cardiometabolic complications. To do.”

Dr. Goossens also said that, coupled with known differences between men and women in lifestyle and response to pharmacological interventions, “this means that gender-specific prevention and treatment strategies may be more effective in both men and women across the gender spectrum.” “This further supports the idea that it may have many health benefits.” obesity. “

Mr. Anderson has received non-financial support (investigational drug donation) from COVIS Pharma in other studies and is the institutional principal investigator for Ionis 678354 at Ionis Pharmaceuticals, Inc. He is also a shareholder and is employed by Werlabs AB. These studies or his employment are not related to his current job. Goossens declared that he had no conflicts of interest.