title: Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls.
abstract: BACKGROUND
  Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on leukocyte activation in patients with a wide range of insulin sensitivity.
  
  
  METHODS
  Leukocyte activation was determined after ingestion of 75 gram glucose in subjects with T2DM, familial combined hyperlipidemia (FCH) and healthy controls. Leukocyte activation markers were measured by flow cytometry. Postprandial changes were calculated as the area under the curve (AUC), and the incremental area under the curve corrected for baseline values (dAUC).
  
  
  RESULTS
  51 Subjects (20 T2DM, 17 FCH and 14 controls) were included. Fasting neutrophil CD66b expression and CD66b-AUC were respectively 36% and 39% higher in T2DM patients than in controls (p=0.004 and p=0.003). Fasting neutrophil CD66b expression correlated positively with glucose-AUC (Spearman's rho 0.481, p<0.001) and HbA1c (rho 0.433, p=0.002). Although fasting monocyte CD11b expression was not significantly different between subjects, monocyte CD11b-AUC was 26% higher in T2DM than in controls (p=0.006). Similar trends were observed for FCH patients. Monocyte CD11b-dAUC correlated positively with glucose-AUC (rho 0.322, p=0.022) and HbA1c (rho 0.319, p=0.023).
  
  
  CONCLUSIONS
  These data suggest that both acute and chronic hyperglycemia, associated with insulin resistance as seen in T2DM and FCH, are involved in the increased fasting and postprandial leukocyte activation observed in these conditions.
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands. Electronic address: m.devries@sfg.nl.
authors.forename: Marijke A
authors.initials: MA
authors.lastname: de Vries
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Arash
authors.initials: A
authors.lastname: Alipour
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Klop
authors.affiliation: Department of Clinical Chemistry, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Gert-Jan M
authors.initials: GJ
authors.lastname: van de Geijn
authors.affiliation: Department of Clinical Chemistry, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Janssen
authors.affiliation: Department of Clinical Chemistry, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Tjin L
authors.initials: TL
authors.lastname: Njo
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Noëlle
authors.initials: N
authors.lastname: van der Meulen
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Arie P
authors.initials: AP
authors.lastname: Rietveld
authors.affiliation: Department of Cardiology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Anho H
authors.initials: AH
authors.lastname: Liem
authors.affiliation: Department of Clinical Pharmacy, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Elsbeth M
authors.initials: EM
authors.lastname: Westerman
authors.affiliation: Department of Endocrinology, Erasmus Medical Center Rotterdam, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Cardiovascular Risk Management, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Manuel Castro
authors.initials: MC
authors.lastname: Cabezas
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D039481:CD11b Antigen / Q000097:blood / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology*; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D001786:Blood Glucose; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006442:Glycated Hemoglobin; C504120:CEACAM8 protein, human; C509295:ITGAM protein, human; C517652:hemoglobin A1c protein, human
keywords: Atherosclerosis; Diabetic complications; Inflammation; Integrin