title: Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus.
abstract: Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.
authors.affiliation: Dipartimento di Medicina Interna, Università di Tor Vergata, Rome, Italy. mtesauro@tiscali.it
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.forename: Stefano
authors.initials: S
authors.lastname: Rizza
authors.forename: Micaela
authors.initials: M
authors.lastname: Iantorno
authors.forename: Umberto
authors.initials: U
authors.lastname: Campia
authors.forename: Carmine
authors.initials: C
authors.lastname: Cardillo
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Roberto
authors.initials: R
authors.lastname: Leo
authors.forename: Mario
authors.initials: M
authors.lastname: Turriziani
authors.forename: Giulio Cesare
authors.initials: GC
authors.lastname: Cocciolillo
authors.forename: Angelo
authors.initials: A
authors.lastname: Fusco
authors.forename: Julio A
authors.initials: JA
authors.lastname: Panza
authors.forename: Angelo
authors.initials: A
authors.lastname: Scuteri
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein