{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:53:07Z","timestamp":1790009587606,"version":"4.0.1"},"reference-count":163,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of the blood\u2013brain barrier (BBB), seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin-independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response, which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote A\u03b2 aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.<\/jats:p>","DOI":"10.3390\/ijms241210069","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T01:32:15Z","timestamp":1686706335000},"page":"10069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Effects of Diabetes Mellitus-Related Dysglycemia on the Functions of Blood\u2013Brain Barrier and the Risk of Dementia"],"prefix":"10.3390","volume":"24","author":[{"given":"Mateusz","family":"W\u0105troba","sequence":"first","affiliation":[{"name":"Laboratory of the Blood\u2013Brain Barrier, Department of Biophysics, Physiology & Pathophysiology, Medical University of Warsaw, Cha\u0142ubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna D.","family":"Grabowska","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood\u2013Brain Barrier, Department of Biophysics, Physiology & Pathophysiology, Medical University of Warsaw, Cha\u0142ubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-060X","authenticated-orcid":false,"given":"Dariusz","family":"Szukiewicz","sequence":"additional","affiliation":[{"name":"Laboratory of the Blood\u2013Brain Barrier, Department of Biophysics, Physiology & Pathophysiology, Medical University of Warsaw, Cha\u0142ubinskiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrendo.2016.105","article-title":"Diabetes mellitus statistics on prevalence and mortality: Facts and fallacies","volume":"12","author":"Zimmet","year":"2016","journal-title":"Nat. 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