title: Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans.
abstract: We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m(2)) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P < 0.01-0.0001), and endothelial function was decreased (P < 0.0005) during euinsulinemia-hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers.
authors.affiliation: Duke University, Chapel Hill, North Carolina; and.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Perkins
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, Baltimore, Maryland.
authors.forename: Nino G
authors.initials: NG
authors.lastname: Joy
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, Baltimore, Maryland.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, Baltimore, Maryland sdavis@medicine.umaryland.edu.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications; D006946:Hyperinsulinism / Q000097:blood* / Q000150:complications; D018836:Inflammation Mediators / Q000097:blood*; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D050177:Overweight / Q000097:blood / Q000503:physiopathology; D014657:Vasculitis / Q000097:blood* / Q000150:complications
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin
keywords: endothelial function; hyperglycemia; hyperinsulinemia; inflammation