Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.

Low-grade inflammation, characterized by increased pro-inflammatory cytokine levels, is present in patients with obesity-linked insulin resistance, hyperglycemia and hyperlipidemia and considered to play a leading role to progression into type 2 diabetes (T2D). In adipose tissue in obese patients an...

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Autores principales:	Helena Cucak, Dorte Vistisen, Daniel Witte, Annelotte Philipsen, Alexander Rosendahl
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/67101a05d48c47e3bd66a50e11bcadf0
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spelling	oai:doaj.org-article:67101a05d48c47e3bd66a50e11bcadf02021-11-25T05:59:20ZReduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.1932-620310.1371/journal.pone.0107140https://doaj.org/article/67101a05d48c47e3bd66a50e11bcadf02014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107140https://doaj.org/toc/1932-6203Low-grade inflammation, characterized by increased pro-inflammatory cytokine levels, is present in patients with obesity-linked insulin resistance, hyperglycemia and hyperlipidemia and considered to play a leading role to progression into type 2 diabetes (T2D). In adipose tissue in obese patients and in pancreatic islets in T2D patients cellular inflammation is present. However, the systemic leukocyte compartment and the circulating endothelial/precursor compartment in patients at risk to develop T2D has so far not been analyzed in detail. To address this, peripheral blood cells from a cohort of 20 subjects at risk to develop diabetes with normal to impaired glucose tolerance were analyzed by flow cytometry using a wide range of cellular markers and correlated to known metabolic risk factors for T2D i.e. fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG), HbA1c, body mass index (BMI), homeostasis model assessment of β-cell function (HOMA-B), homeostasis model assessment of insulin sensitivity (HOMA-IS) and fasting insulin (FI). The four highest ranked cell markers for each risk factor were identified by random forest analysis. In the cohort, a significant negative correlation between the number of TLR4(+) CD4 T cells and increased FPG was demonstrated. Similarly, with increased BMI the frequency of TLR4(+) B cells was significantly decreased, as was the frequency of IL-21R(+) CD4 T cells. Unlinked to metabolic risk factors, the frequency of regulatory T cells was reduced and TLR4(+) CD4 T cells were increased with age. Taken together, in this small cohort of subjects at risk to develop T2D, a modulation of the circulating immune cell pool was demonstrated to correlate with risk factors like FPG and BMI. This may provide novel insights into the inflammatory mechanisms involved in the progression to diabetes in subjects at risk.Helena CucakDorte VistisenDaniel WitteAnnelotte PhilipsenAlexander RosendahlPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107140 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Helena Cucak Dorte Vistisen Daniel Witte Annelotte Philipsen Alexander Rosendahl Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
description	Low-grade inflammation, characterized by increased pro-inflammatory cytokine levels, is present in patients with obesity-linked insulin resistance, hyperglycemia and hyperlipidemia and considered to play a leading role to progression into type 2 diabetes (T2D). In adipose tissue in obese patients and in pancreatic islets in T2D patients cellular inflammation is present. However, the systemic leukocyte compartment and the circulating endothelial/precursor compartment in patients at risk to develop T2D has so far not been analyzed in detail. To address this, peripheral blood cells from a cohort of 20 subjects at risk to develop diabetes with normal to impaired glucose tolerance were analyzed by flow cytometry using a wide range of cellular markers and correlated to known metabolic risk factors for T2D i.e. fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG), HbA1c, body mass index (BMI), homeostasis model assessment of β-cell function (HOMA-B), homeostasis model assessment of insulin sensitivity (HOMA-IS) and fasting insulin (FI). The four highest ranked cell markers for each risk factor were identified by random forest analysis. In the cohort, a significant negative correlation between the number of TLR4(+) CD4 T cells and increased FPG was demonstrated. Similarly, with increased BMI the frequency of TLR4(+) B cells was significantly decreased, as was the frequency of IL-21R(+) CD4 T cells. Unlinked to metabolic risk factors, the frequency of regulatory T cells was reduced and TLR4(+) CD4 T cells were increased with age. Taken together, in this small cohort of subjects at risk to develop T2D, a modulation of the circulating immune cell pool was demonstrated to correlate with risk factors like FPG and BMI. This may provide novel insights into the inflammatory mechanisms involved in the progression to diabetes in subjects at risk.
format	article
author	Helena Cucak Dorte Vistisen Daniel Witte Annelotte Philipsen Alexander Rosendahl
author_facet	Helena Cucak Dorte Vistisen Daniel Witte Annelotte Philipsen Alexander Rosendahl
author_sort	Helena Cucak
title	Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
title_short	Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
title_full	Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
title_fullStr	Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
title_full_unstemmed	Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
title_sort	reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/67101a05d48c47e3bd66a50e11bcadf0
work_keys_str_mv	AT helenacucak reductionofspecificcirculatinglymphocytepopulationswithmetabolicriskfactorsinpatientsatrisktodeveloptype2diabetes AT dortevistisen reductionofspecificcirculatinglymphocytepopulationswithmetabolicriskfactorsinpatientsatrisktodeveloptype2diabetes AT danielwitte reductionofspecificcirculatinglymphocytepopulationswithmetabolicriskfactorsinpatientsatrisktodeveloptype2diabetes AT annelottephilipsen reductionofspecificcirculatinglymphocytepopulationswithmetabolicriskfactorsinpatientsatrisktodeveloptype2diabetes AT alexanderrosendahl reductionofspecificcirculatinglymphocytepopulationswithmetabolicriskfactorsinpatientsatrisktodeveloptype2diabetes
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Reduction of specific circulating lymphocyte populations with metabolic risk factors in patients at risk to develop type 2 diabetes.

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