Endocrine Abstracts

Introduction: Diabetes mellitus is known as a factor of cognitive impairment. The risk of dementia in patients with type 2 diabetes mellitus (T2DM) increases almost twice. The results of epidemiological, visualization and autopsy studies showed the presence of both cerebrovascular and neurodegenerative mechanisms of brain lesions. Cell death of key substrates – neurons and endothelial cells lays in the basis of the formation of cerebral disorders. Granzyme B (GrB) is a serine protease, which exerts both intracellular apoptotic and extracellular functions, leading to tissue injury, inflammation and repair.

The aim of the study was to find out role of the granzyme-induced mechanisms of programmed cell death in the development of cognitive impairment in patients with type 2 diabetes.

Material and Methods: 70 patients with cognitive impairmentin T2DM and 26 healthy individuals who formedthe control group were examined. Patients were classified using neuropsychological assessment tests. The Mini-mental State Examination test (MMSE), Montreal Cognitive Assessment (MoCA) test and the determination of cognitive-induced potentials were used to evaluate cognitive functions. Serum Granzyme B (GrB) was measured by Human Granzyme B Elisa kit (Bender MedSystems).

Results: Mild cognitive impairment was diagnosed in 47 patients with T2DM, dementia in 23 subjects. T2DM patients had 56% higher serum level of GrB than the control group (P = 0.03). The changes were statistically insignificant in the group of patients with mild cognitive impairment, while in subjects with dementia the level of GrB was almost twice higher compared to the control group (P = 0.04). Positive correlations were established between the MMSE and MoCA tests results of patients with T2DM and levels of GrB, direct correlation – the latent period P300 and levels of GrB (P < 0.05). Thus, serine protease GrB can play a role in the mechanisms of brain damage in T2DM by converting procaspase 3 to active caspase 3. Activation of cytotoxic T- cells leads to the release of perforine and granzymes from their granules. Perforine forms in the plasma membrane of target cells the pores through which granzymes penetrate. Also, recent studies have shown that GrB plays an significant role in the processes of destabilization of atherosclerotic plaques, that important in the aspect of vascular dementia in DM.

Conclusion: Cognitive impairment in patients with type 2 diabetes is accompanied by an increase in granzyme-induced apoptotic processes.