0
0
New research presented at the European Congress on Obesity (ECO) 2024 suggests that differences in how adipose tissue responds to insulin may account for the higher prevalence of type 2 diabetes in men compared to women with obesity.
The study, led by Dr. Daniel P. Andersson, an endocrinologist at Karolinska University Hospital Huddinge, revealed that men exhibit greater adipose tissue insulin resistance. Specifically, fat cells from men with a body mass index (BMI) ≥ 30 required a tenfold higher concentration of insulin to block the breakdown of triglycerides into free fatty acids and glycerol. Additionally, this blocking mechanism was less effective in men than in women.
“We found that men living with obesity had increased adipose insulin resistance and higher levels of free fatty acids in the blood,” Dr. Andersson told Medscape Medical News. He emphasized that this was primarily due to the reduced efficacy of insulin in blocking triglyceride breakdown in men’s adipose tissue, rather than differences in storage capacity between the sexes. “These findings could be part of the explanation as to why type 2 diabetes is more common in men than in women,” he added.
Insulin’s Role in Fat Storage and Release
Insulin plays a crucial role in both storing and inhibiting the release of lipids. It stimulates the conversion of free fatty acids into triglycerides within adipocytes and inhibits their breakdown back into free fatty acids. Insulin resistance diminishes this inhibitory effect, leading to an increased release of free fatty acids into the bloodstream. This chronic exposure to excess fatty acids can decrease muscle glucose uptake, increase liver gluconeogenesis, and reduce insulin secretion by the pancreas, perpetuating hyperglycemia and further insulin resistance.
Key Differences Between Men and Women
The researchers measured the adipose insulin resistance index (AdipoIR) in the subcutaneous abdominal fat of 2344 women and 787 men, with a mean age of 44 years and mean BMI of 35. They found that men had higher AdipoIR values than women, but only in those with a BMI ≥ 30. This pattern was consistent regardless of physical activity levels, cardiometabolic disease, or nicotine use.
In a subgroup of 259 women and 54 men with obesity, isolated adipocytes were examined to compare insulin effects. The study found that a tenfold higher concentration of insulin was needed to block triglyceride breakdown in men compared to women, and the blockage was less effective in men.
Implications and Future Directions
Dr. Andersson highlighted that type 2 diabetes is linked to adipose tissue, though the exact mechanisms remain unclear. “Removing adipose tissue doesn’t improve insulin sensitivity, so it likely involves the health status of fat cells. Changing fat cell function through medication, diet, or bariatric surgery could improve glucose control by fine-tuning lipolysis and lipogenesis,” he explained.
Commenting on the study, Dr. Gijs Goossens, a professor of cardiometabolic physiology of obesity at Maastricht University Medical Center+, noted that premenopausal women with obesity are relatively protected against cardiometabolic complications compared to men of similar age and BMI. He attributed this to a more favorable body fat distribution and higher insulin sensitivity in women.
“The finding that insulin resistance in abdominal subcutaneous adipose tissue is more pronounced in men than women with obesity provides further evidence of significant sex differences in the etiology of obesity-related cardiometabolic complications,” Dr. Goossens said. He suggested that these insights support the development of sex-specific prevention and treatment strategies for obesity and its associated health risks.
The full findings have been published in the International Journal of Obesity.
