Circulating miR-132-3p and Neuronal PI3K–Akt Signaling in Cognitive Dysfunction in Newly Diagnosed Type 2 Diabetes: Clinical and Experimental Evidence

Type 2 diabetes is a common chronic disease that affects millions of people worldwide. Importantly, it is often diagnosed only when complications have already begun to develop, highlighting the need for earlier detection and timely intervention in order to prevent or delay disease progression and associated comorbidities. Traditionally, type 2 diabetes has been primarily associated with cardiovascular and renal complications. However, in recent years, growing evidence has shown that diabetes can also affect the brain, increasing the risk of cognitive decline and dementia. The mechanisms underlying this association are complex and multifactorial. Chronic hyperglycaemia can induce cellular damage, promote inflammation, and impair insulin signalling not only in peripheral tissues but also in the central nervous system. Insulin plays a crucial role in brain function, particularly in processes such as learning, attention, memory, and executive function. Conversely, brain insulin resistance has been increasingly recognized as a contributing factor to cognitive impairment. Therefore, this thesis explores brain changes associated with diabetes by combining clinical research with experimental studies on neuronal cells. In the clinical component of this research, we analysed a wide range of hematochemical parameters in patients with newly diagnosed type 2 diabetes, who were drug-naïve at baseline and subsequently treated with standard oral antidiabetic therapy for one year, according to clinical practice. Particular attention was given to a small regulatory molecule known as microRNA-132. MicroRNAs are short, non-coding RNA molecules that act as fine tuners of gene expression and can circulate in the bloodstream, providing valuable insight into ongoing physiological and pathological processes. Our findings revealed that circulating levels of microRNA-132 are modulated following diabetes treatment, suggesting its potential role as a biomarker for monitoring both metabolic status and cognitive health.