Öz
Amaç
Kognitif bozukluk tip 2 diyabetes mellitusun (T2DM) bir komplikasyonu olarak giderek daha fazla kabul görmekte ve literatürde antihiperglisemik tedavinin bilişsel işlevleri de iyileştirebileceği tartışılmaktadır. Bu konudaki özellikle sodyum-glukoz-kotransporter-2 (SGLT2) inhibitörleri ile ilgili klinik araştırmalar sınırlıdır. Beyin-kaynaklı nörotrofik faktör (BDNF), kognitif işlevler ve glukoz metabolizması için önemli bir proteindir. Araştırmamızın amacı SGLT2 inhibitörü kullananlarda kognitif performans ve BDNF düzeylerini incelemektir.
Yöntemler
Bu kesitsel çalışma, metformin kullanan 41 hasta ve SGLT2 inhibitörü kullanan 45 hasta olmak üzere toplam 86 T2DM hastası ile gerçekleştirilmiştir. Hastaların kognitif performansı Montreal bilişsel değerlendirme (MoCA) testi ile serum BDNF düzeyleri ELISA yöntemi kullanılarak ölçüldü.
Bulgular
SGLT2 inhibitörü kullananlar ile metformin kullananlar arasında MoCA toplam skorlarında ve Vizuospasyal/Yürütücü, İsimlendirme, Dikkat, Dil, Soyutlama, Hafıza ve Oryantasyon alt alanlarında anlamlı bir fark bulunmadı. SGLT2 inhibitörü grubunda BDNF seviyeleri nispeten daha yüksek olmasına rağmen, fark istatistiksel olarak anlamlı değildi. BDNF düzeyleri ile mikroalbümin, mikroalbümin/kreatinin, glomerüler filtrasyon hızı (eGFR), lenfosit düzeyleri arasında anlamlı korelasyonlar gözlenmiştir. Lineer regresyon analizine göre, eGFR düzeylerinin BDNF düzeylerini öngörmedeki etkisi anlamlıdır.
Sonuç
Sonuçlarımız, bilişsel performans BDNF düzeylerinin metformin ve SGLT2 inhibitörleri kullanıcıları arasında benzer olduğunu göstermiştir. SGLT2 inhibitörlerinin T2DM’de bilişsel işlevler üzerindeki etkisini araştıran klinik araştırmalar sınırlıdır. SGLT2 inhibitörleri ile gelecekte yapılacak prospektif takip çalışmaları daha kapsamlı bilgi sağlayabilir.
Anahtar Kelimeler: Sodyum glukoz ko-trasnporter 2 inhibitörleri, kognisyon, tip 2 diyabet, beyin kaynaklı nörotrofik faktör
Kaynakça
Singh DD, Shati AA, Alfaifi MY, Elbehairi SEI, Han I, Choi EH, et al. Development of dementia in type 2 diabetes patients: mechanisms of insulin resistance and antidiabetic drug development. Cells. 2022;11:3767.
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53:1937-42.
Yaffe K, Falvey C, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S, et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol. 2012;69:1170-5.
Stoeckel LE, Arvanitakis Z, Gandy S, Small D, Kahn CR, Pascual-Leone A, et al. Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction. F1000Res. 2016;5:353.
Kim JY, Ku YS, Kim HJ, Trinh NT, Kim W, Jeong B, et al. Oral diabetes medication and risk of dementia in elderly patients with type 2 diabetes. Diabetes Res Clin Pract. 2019;154:116-23.
Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects. J Pharmacol Sci. 2016;130:159-69.
Mui JV, Zhou J, Lee S, Leung KSK, Lee TTL, Chou OHI, et al. Sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP4) inhibitors for new-onset dementia: a propensity score-matched population-based study with competing risk analysis. Front Cardiovasc Med. 2021;8:747620.
Mone P, Lombardi A, Gambardella J, Pansini A, Macina G, Morgante M, et al. Empagliflozin improves cognitive impairment in frail older adults with type 2 diabetes and heart failure with preserved ejection fraction. Diabetes Care. 2022;45:1247-51.
Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, et al. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007;50:431-8.
Rozanska O, Uruska A, Zozulinska-Ziolkiewicz D. Brain-derived neurotrophic factor and diabetes. Int J Mol Sci. 2020;21:841.
Velioglu HA, Hanoglu L, Bayraktaroglu Z, Toprak G, Guler EM, Bektay MY, et al. Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer's disease: Possible role of BDNF and oxidative stress. Neurobiol Learn Mem. 2021;180:107410.
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-9.
Ozdilek B, Kenangil G. Validation of the Turkish version of the Montreal Cognitive Assessment Scale (MoCA-TR) in patients with Parkinson's disease. Clin Neuropsychol. 2014;28:333-43.
Biessels GJ, Whitmer RA. Cognitive dysfunction in diabetes: how to implement emerging guidelines. Diabetologia. 2020;63:3-9.
Hierro-Bujalance C, Infante-Garcia C, Del Marco A, Herrera M, Carranza-Naval MJ, Suarez J, et al. Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes. Alzheimers Res Ther. 2020;12:40.
Khan T, Khan S, Akhtar M, Ali J, Najmi AK. Empagliflozin nanoparticles attenuates type2 diabetes induced cognitive impairment via oxidative stress and inflammatory pathway in high fructose diet induced hyperglycemic mice. Neurochem Int. 2021;150:105158.
Lin B, Koibuchi N, Hasegawa Y, Sueta D, Toyama K, Uekawa K, et al. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol. 2014;13:148.
Hayden MR, Grant DG, Aroor AR, DeMarco VG. Empagliflozin Ameliorates type 2 diabetes-induced ultrastructural remodeling of the neurovascular unit and neuroglia in the female db/db mouse. Brain Sci. 2019;9:57.
Sa-Nguanmoo P, Tanajak P, Kerdphoo S, Jaiwongkam T, Pratchayasakul W, Chattipakorn N, et al. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats. Toxicol Appl Pharmacol. 2017;333:43-50.
Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, et al. Enhancement of impaired olfactory neural activation and cognitive capacity by liraglutide, but not dapagliflozin or acarbose, in patients with type 2 diabetes: a 16-week randomized parallel comparative study. Diabetes Care. 2022;45:1201-10.
Perna S, Mainardi M, Astrone P, Gozzer C, Biava A, Bacchio R, et al. 12-month effects of incretins versus SGLT2-Inhibitors on cognitive performance and metabolic profile. A randomized clinical trial in the elderly with Type-2 diabetes mellitus. Clin Pharmacol. 2018;10:141-51.
Borzì AM, Condorelli G, Biondi A, Basile F, Vicari ESD, Buscemi C, et al. Effects of vildagliptin, a DPP-4 inhibitor, in elderly diabetic patients with mild cognitive impairment. Arch Gerontol Geriatr. 2019;84:103896.
Watson KT, Wroolie TE, Tong G, Foland-Ross LC, Frangou S, Singh M, et al. Neural correlates of liraglutide effects in persons at risk for Alzheimer's disease. Behav Brain Res. 2019;356:271-8.
Meng J, Yan R, Zhang C, Bai X, Yang X, Yang Y, et al. Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus. Lipids Health Dis. 2023;22:219.
Wu CY, Iskander C, Wang C, Xiong LY, Shah BR, Edwards JD, et al. Association of sulfonylureas with the risk of dementia: A population-based cohort study. J Am Geriatr Soc. 2023;71:3059-70.
Lin Y, Wang K, Ma C, Wang X, Gong Z, Zhang R, et al. Corrigendum: evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Front Aging Neurosci. 2018;10:322.
Scherrer JF, Salas J, Floyd JS, Farr SA, Morley JE, Dublin S. Metformin and sulfonylurea use and risk of incident dementia. Mayo Clin Proc. 2019;94:1444-56.
Shi Q, Liu S, Fonseca VA, Thethi TK, Shi L. Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus. BMJ Open. 2019;9:e024954.
Newby D, Linden AB, Fernandes M, Molero Y, Winchester L, Sproviero W, et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10:e003036.
Pomilio C, Pérez NG, Calandri I, Crivelli L, Allegri R; ADNI Alzheimer’s Disease Neuroimaging Initiative, et al. Diabetic patients treated with metformin during early stages of Alzheimer's disease show a better integral performance: data from ADNI study. Geroscience. 2022;44:1791-805.
Biessels GJ, Nobili F, Teunissen CE, Simó R, Scheltens P. Understanding multifactorial brain changes in type 2 diabetes: a biomarker perspective. Lancet Neurol. 2020;19:699-710.
Movassat J, Delangre E, Liu J, Gu Y, Janel N. Hypothesis and theory: circulating Alzheimer's-related biomarkers in type 2 diabetes. Insight from the Goto-Kakizaki rat. Front Neurol. 2019;10:649.
