title: Reduced arterial stiffness after weight loss in obese type 2 diabetes and impaired glucose tolerance: the role of immune cell activation and insulin resistance.
abstract: Weight loss after bariatric surgery reduces cardiac risk and morbidity. We examined weight loss effects on arterial stiffness in morbidly obese subjects, in relation to cytokines, circulating and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)-based immune cells and gene expression. Obese subjects with type 2 diabetes mellitus (T2D) or impaired glucose tolerance (n = 14, mean ± SEM body mass index 42.9 kg/m(2)) underwent 24 weeks' caloric restriction, with gastric banding at 12 weeks. Measures were: arterial augmentation index (AIx), insulin resistance, circulating cytokines, immune cell activation markers, and SAT and VAT cytokine gene expression. Weight loss reduced AIx by 20% (p = 0.007), with falls in s-selectin (p = 0.001) and inter-cellular adhesion molecule (p = 0.04). Improved AIx related to reduced surface expression of the interleukin (IL)-2 receptor on T-lymphocytes (TL-IL2R) and granulocyte adhesion markers (r = 0.59, 0.64, respectively, p < 0.04). Higher VAT expression of interferon-γ and monocyte chemoattractant protein-1 associated with a blunted AIx response. A model of TL-IL2R expression, waist, weight and insulin resistance explained 73% of the variance in AIx reduction (p = 0.005). In morbidly obese dysglycaemic subjects, modest weight loss reduces arterial stiffness, the magnitude of which relates to improved markers of inflammation.
authors.affiliation: Diabetes Program, Garvan Institute of Medical Research, Darlinghurst, Australia. k.samaras@garvan.org.au
authors.forename: Katherine
authors.initials: K
authors.lastname: Samaras
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
authors.forename: Ping N
authors.initials: PN
authors.lastname: Lee
authors.forename: Alicia
authors.initials: A
authors.lastname: Jenkins
authors.forename: Natalia K
authors.initials: NK
authors.lastname: Botelho
authors.forename: Anthea
authors.initials: A
authors.lastname: Bakopanos
authors.forename: Reginald V
authors.initials: RV
authors.lastname: Lord
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayward
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D062186:Arterial Pressure / Q000502:physiology*; D050110:Bariatric Surgery; D015415:Biomarkers / Q000378:metabolism; D001795:Blood Pressure Determination / Q000379:methods; D031204:Caloric Restriction; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009765:Obesity / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D050151:Subcutaneous Fat / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C108355:CCL20 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D016207:Cytokines