Diabetes Mellitus (DM) is one of the most common chronic conditions among the population, especially DM type 2, which accounts for about 90 % of the recorded cases.1 According to the International Diabetes Federation, approximately 537 million people are estimated to live with this disease worldwide, and this number is expected to increase substantially over the years, reaching 643 million people by 2030.2

DM, excess body fat, and cognitive dysfunction seem to be able to coexist. The excess fat is directly associated with dysregulation of adipocyte activity, leading to increased fat accumulation and abnormal production of adipokines, causing an imbalance between pro-inflammatory factors, such as interleukins (IL) - 1β, IL-6, TNF-α, and leptin, and reduced levels of anti-inflammatory factors, such as adiponectin. These alterations promote systemic dysregulation, with metabolic disturbances and endocrine alterations.3,4

This systemic dysregulation leads to alterations in the functioning of the blood-brain barrier (BBB), by increasing its permeability and resulting in neurological disturbances due to glucose-induced neurotoxicity. The mechanisms of neurotoxicity can work by three pathways: impaired glucose transport, dysregulation of glucose transporter 1 (Glut-1), disruption of insulin movement from the endothelial cells to the brain, and elevated serum levels of leptin. Additionally, there is microglial function dysregulation, favoring the release of pro-inflammatory cytokines and the infiltration of multiple immune cells, particularly macrophages, and monocytes, leading to neuronal apoptosis, neuroinflammation, and, in the long term, cognitive impairment.1,3,5

Some epidemiological studies introduce the term obesity paradox, suggesting a bidirectional relationship between excess body fat and cognitive impairment, which is detrimental to middle-aged individuals.6, 7, 8 However, in older individuals, a higher BMI may be associated with better cognition, leading to the hypothesis that weight reduction could affect the development of neurological functions.9, 10, 11

However, evidence supporting the relationship between excess body fat and cognitive decline in individuals diagnosed with DM is scarce and inconclusive. Therefore, there is a need for further studies aiming to understand the mechanisms involved in the cognitive impairment of DM and the role of body fat in this relationship. Thus, we aimed to investigate the relationship between body fat and cognitive function in individuals with DM.