Depression, type 2 diabetes mellitus, and omega-3 polyunsaturated fatty acids

The risk of depression in patients with type 2 diabetes mellitus (T2DM) is 1.5–2 times higher than in people without carbohydrate metabolism disorders. In addition, adults with prediabetes are more likely to have strokes and dementia, which indicates the onset of pathophysiological changes in the central nervous system even before clinical manifestation of T2DM. Se­veral epidemiological studies have shown that adequate intake of ω-3 polyunsaturated fatty acids (PUFAs) or their increased serum levels correlate with a reduced risk of depression. In addition, a significant number of studies also indicate that the ratio of ω-3 PUFA to ω-6 PUFA intake is inversely related to the risk of developing depressive symptoms. The results of a meta-analysis of studies have demonstrated that ω-3 PUFAs contribute to the improvement of glycemic control and reduction of insulin resistance in patients with T2DM. Ω-3 PUFAs affect lipid composition, regulate membrane fluidity and membrane processes in cells, promote the formation of protein complexes in membranes and lipid domains, influence neurotransmitters and neuroendocrine exocytosis, and support microglia activity during phagocytosis. They can enhance antioxidant potential, generate anti-inflammatory metabolites, and regulate inflammatory signaling pathways. ω-3 PUFAs regulate signaling pathways, affect neurotransmitter systems, modulate gene expression, and are involved in the processes of proliferation, differentiation, growth, development, aging, and apoptosis. Thanks to these mechanisms, ω-3 PUFAs have a significant impact on neurobiological processes associated with mood regulation in the central nervous system. In addition, they improve the status in neuroinflammation, oxidative stress, insulin resistance, neurodegenerative processes, neuroplasticity disorders, and influence neurotransmitter system functioning. The combination of these effects may play an important role in the prevention and treatment of depression in patients with T2DM. The main purpose of this review is to analyze the importance of ω-3 PUFAs in the prevention and treatment of comorbid conditions, including depression and T2DM. In addition, current trends are discussed, and promising areas for future research in this field are outlined. The search was conducted in Scopus, ScienceDirect (from Elsevier), and PubMed, including MEDLINE databases. The keywords used were “depression”, “type 2 diabetes mellitus”, and “ω-3 polyunsaturated fatty acids”. A manual search of the bibliography of publications was used to identify research results that could not be found during the online search.