{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:11:19Z","timestamp":1771488679296,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T00:00:00Z","timestamp":1608854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","award":["1701090120-P"],"award-info":[{"award-number":["1701090120-P"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012001","name":"Al Jalila Foundation","doi-asserted-by":"publisher","award":["AJF2018082"],"award-info":[{"award-number":["AJF2018082"]}],"id":[{"id":"10.13039\/100012001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The recurrence of hypoglycemic episodes leads to attenuation of the normal counter-regulatory mechanisms that are controlled by the hypothalamus, which results in hypoglycemia unawareness (HU). In this case report, we described for the first time the differential expression of TNF-\u03b1, IL-1\u03b2, IL-6, and IFN-\u03b3 in a blood sample that was taken from a 27-year-old patient with type 1 diabetes mellitus (T1DM) who was diagnosed with HU. The anti-diabetic regimen is currently based on insulin injection, but the patient is planning to start the use of an insulin pump to have better control of glucose levels. Our results showed a trend toward an increase in the expression of IL-1\u03b2, IL-6, and IFN-\u03b3 in T1DM patient with HU. However, the mRNA level of TNF-\u03b1 showed a significant decrease. These observations suggest that systemic inflammation could be an underlying cause of HU.<\/jats:p>","DOI":"10.3390\/brainsci11010017","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T09:30:19Z","timestamp":1608888619000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Expression of Inflammatory Markers in Hypoglycemia Unawareness Associated with Type 1 Diabetes: A Case Report"],"prefix":"10.3390","volume":"11","author":[{"given":"Yousef","family":"Al Zoubi","sequence":"first","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE"},{"name":"Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1554-6319","authenticated-orcid":false,"given":"Bashair M.","family":"Mussa","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0479-180X","authenticated-orcid":false,"given":"Ankita","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8774-0014","authenticated-orcid":false,"given":"Abdul Khader","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elamin","family":"Abdelgadir","sequence":"additional","affiliation":[{"name":"Dubai Health Authority, Dubai Hospital, Dubai 4545, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaaeldin","family":"Bashier","sequence":"additional","affiliation":[{"name":"Dubai Health Authority, Dubai Hospital, Dubai 4545, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatheya Al","family":"Awadi","sequence":"additional","affiliation":[{"name":"Dubai Health Authority, Dubai Hospital, Dubai 4545, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah","family":"Abusnana","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology Department, University Hospital Sharjah, Sharjah 72772, UAE"},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2337\/db08-1224","article-title":"Small decrements in systemic glucose provoke increases in hypothalamic blood flow prior to the release of counterregulatory hormones","volume":"58","author":"Page","year":"2008","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.bbadis.2008.10.013","article-title":"A look inside the diabetic brain: Contributors to diabetes-induced brain aging","volume":"1792","author":"Wrighten","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_3","first-page":"E1115","article-title":"Hypoglycemia-associated autonomic failure in diabetes","volume":"281","author":"Cryer","year":"2001","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kamenov, Z., and Traykov, L. (2012). Diabetic autonomic neuropathy. Advances in Experimental Medicine and Biology, Springer.","DOI":"10.1007\/978-1-4614-5441-0_15"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhou, C., Teegala, S.B., Khan, B.A., Gonzalez, C., and Routh, V.H. (2018). Hypoglycemia: Role of hypothalamic glucose-inhibited (GI) neurons in detection and correction. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00192"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cryer, P.E. (2011). The prevention and correction of hypoglycemia. Compr. Physiol., 1057\u20131092.","DOI":"10.1002\/cphy.cp070235"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.5114\/pedm.2018.80994","article-title":"Hypoglycaemia unawareness in patients with type 1 diabetes","volume":"2018","author":"Szadkowska","year":"2018","journal-title":"Pediatr. Endocrinol. Diabetes Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1172\/JCI97696","article-title":"Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia","volume":"128","author":"Hwang","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1464-5491.2008.02413.x","article-title":"Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes","volume":"25","author":"Geddes","year":"2008","journal-title":"Diabet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3592","DOI":"10.2337\/diabetes.54.12.3592","article-title":"Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes","volume":"54","author":"Cryer","year":"2005","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/9185272","article-title":"Low glucose concentrations induce a similar inflammatory response in monocytes from type 2 diabetic patients and healthy subjects","volume":"2017","author":"Piarulli","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00592-015-0713-4","article-title":"Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study","volume":"52","author":"Giorda","year":"2015","journal-title":"Acta Diabetol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.metabol.2008.10.018","article-title":"Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects","volume":"58","author":"Nematollahi","year":"2009","journal-title":"Metabolism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.atherosclerosis.2016.05.002","article-title":"Hypoglycemic episodes are associated with inflammatory status in patients with type 1 diabetes mellitus","volume":"251","author":"Matejko","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.nbd.2009.11.018","article-title":"Chronic expression of low levels of tumor necrosis factor-\u03b1 in the substantia nigra elicits progressive neurodegeneration, delayed motor symptoms and microglia\/macrophage activation","volume":"37","author":"Ezcurra","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.2337\/dc09-0354","article-title":"Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals","volume":"33","author":"Joy","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fphys.2018.00104","article-title":"Expression of proinflammatory cytokines is upregulated in the hypothalamic paraventricular nucleus of dahl salt-sensitive hypertensive rats","volume":"9","author":"Jiang","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.1523\/JNEUROSCI.0734-18.2018","article-title":"Suppressing interferon-\u03b3 stimulates microglial responses and repair of microbleeds in the diabetic brain","volume":"38","author":"Taylor","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4632","DOI":"10.1523\/JNEUROSCI.3046-18.2019","article-title":"Interferon-\u03b3 as a potential link between diabetes mellitus and dementia","volume":"39","author":"Cozachenco","year":"2019","journal-title":"J. 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