Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes

Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion...

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Autores principales:	Abu Saleh Md Moin, Manjula Nandakumar, Ahmed Al-Qaissi, Thozhukat Sathyapalan, Stephen L. Atkin, Alexandra E. Butler
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	type 2 diabetes endothelial proteins biomarkers ischemic stroke predictive biomarkers Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e95c31b9554649eaaaa91e1455efafca
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spelling	oai:doaj.org-article:e95c31b9554649eaaaa91e1455efafca2021-12-01T23:40:56ZPotential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes2296-889X10.3389/fmolb.2021.744459https://doaj.org/article/e95c31b9554649eaaaa91e1455efafca2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.744459/fullhttps://doaj.org/toc/2296-889XBackground and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS.Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose <2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1).Results: At baseline (BL), PPBP (p < 0.05), THBS1 (p < 0.05), and CDH1 (p < 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p < 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels.Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk.Clinical trial reg. no: NCT03102801.Abu Saleh Md MoinManjula NandakumarAhmed Al-QaissiAhmed Al-QaissiThozhukat SathyapalanStephen L. AtkinAlexandra E. ButlerFrontiers Media S.A.articletype 2 diabetesendothelial proteinsbiomarkersischemic strokepredictive biomarkersBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes endothelial proteins biomarkers ischemic stroke predictive biomarkers Biology (General) QH301-705.5
spellingShingle	type 2 diabetes endothelial proteins biomarkers ischemic stroke predictive biomarkers Biology (General) QH301-705.5 Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
description	Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS.Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose <2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1).Results: At baseline (BL), PPBP (p < 0.05), THBS1 (p < 0.05), and CDH1 (p < 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p < 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels.Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk.Clinical trial reg. no: NCT03102801.
format	article
author	Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler
author_facet	Abu Saleh Md Moin Manjula Nandakumar Ahmed Al-Qaissi Ahmed Al-Qaissi Thozhukat Sathyapalan Stephen L. Atkin Alexandra E. Butler
author_sort	Abu Saleh Md Moin
title	Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
title_short	Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
title_full	Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
title_fullStr	Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
title_full_unstemmed	Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
title_sort	potential biomarkers to predict acute ischemic stroke in type 2 diabetes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e95c31b9554649eaaaa91e1455efafca
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Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes

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