Endocrine Abstracts

Background and Aim: Type 2 diabetes mellitus (DM) treatment guidelines give preference to drugs with proven cardioprotective effect, which include sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). GLP-1RA are known to reduce the stroke risk. Data on SGLT-2i effect on the brain, in conditions of both acute and chronic cerebrovascular disorders, are less complete. The aim of our study was to evaluate the effect of high-selective SGLT-2i empagliflozin (EMPA) and low-selective SGLT-2i canagliflozin (CANA) on the central nervous system biochemical and functional parameters in type 2 diabetic patients.

Materials and Methods: The study included type 2 DM patients aged 45-75 on metformin monotherapy. The following groups were formed: group 1 (n=12) - patients with target glycated hemoglobin (HbA1c) level who did not undergo therapy correction, groups 2 and 3 (n=14 and n=12, respectively) - patients with HbA1c exceeding target no more than 2.5%. In group 2 EMPA therapy was initiated, in group 3 CANA therapy. Control group (n=18) of healthy volunteers was also created. In all groups, the levels of HbA1c, neuron-specific enolase (NSE), neurofilament light chains (NLC) were determined initially, cognitive assessment scales (MOCA, MMSE) were used. In groups 2 and 3 these parameters were also evaluated after 3 and 6 months.

Results: Baseline NSE level in DM patients was higher than in healthy volunteers, regardless of glycemic control (2.76 (2.47; 3.92) ng/ml in the control group, 3.22 (2.61; 4.16) ng/ml in DM with target HbA1c, 3.58 (3.11; 3.73) ng/ml in DM with non-target HbA1c). EMPA addition did not cause changes in NSE, while CANA administration significantly reduced NSE (after 6 months it was 2.73 (2.00; 2.92) ng/ml). The NLC in DM patients with target HbA1c initially did not differ from that in control group (4.5 (3.31; 5.56) and 4.13 (3.31; 5.31) ng/ml, respectively), but was elevated in patients with non-targeted HbA1c (5.25 (3.75; 6.25) ng/ml). Both EMPA and CANA caused this parameter decrease, while CANA effect was more pronounced - NLC after 6 months of EMPA therapy was 4.50 (3.45; 4.50) ng/ml, CANA - 2.00 (1.95; 2.20) ng/ml. DM, even with target HbA1c, led to cognitive deficits when assessed by MOCA and MMSE. EMPA and CANA significantly improved these parameters over time. Negative correlation was found between NLC level and the points in MOCA and MMSE.

Conclusions: DM, even with satisfactory glycemic control, has a negative impact on the brain, which is manifested by neuronal damage markers increase and cognitive dysfunction. High- and low-selective SGLT-2i have a neuroprotective effect, which is probably more pronounced in low-selective CANA.