title: Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome.
abstract: OBJECTIVE
  Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS; We studied 24 obese subjects (9 men and 15 women, age 49.3 +/- 1.9 years, BMI 36.7 +/- 0.94 kg/m(2), mean +/- SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen.
  
  
  RESULTS
  This intervention resulted in 6.6 +/- 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 +/- 0.36 vs. 1.9 +/- 0.33 [10(-4) x min(-1) x ( microU ml(-1))], P < 0.001). FMD significantly improved (12.9 +/- 1.2% vs. 7.9 +/- 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 +/- 7.7 vs. 265.6 +/- 9.3 ng/ml, P = 0.018 and 36.2 +/- 3.6 vs. 48.6 +/- 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R(2) = 0.47, P = 0.001).
  
  
  CONCLUSIONS
  We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.
authors.affiliation: Clinical Research Center, Joslin Diabetes Center, the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. osama.handy@joslin.harvard.edu
authors.forename: Osama
authors.initials: O
authors.lastname: Hamdy
authors.forename: Sarah
authors.initials: S
authors.lastname: Ledbury
authors.forename: Cathy
authors.initials: C
authors.lastname: Mullooly
authors.forename: Catherine
authors.initials: C
authors.lastname: Jarema
authors.forename: Satoko
authors.initials: S
authors.lastname: Porter
authors.forename: Kerry
authors.initials: K
authors.lastname: Ovalle
authors.forename: Amr
authors.initials: A
authors.lastname: Moussa
authors.forename: Antonella
authors.initials: A
authors.lastname: Caselli
authors.forename: A Enrique
authors.initials: AE
authors.lastname: Caballero
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Economides
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
authors.forename: Edward S
authors.initials: ES
authors.lastname: Horton
mesh_terms: D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D015992:Body Mass Index; D001916:Brachial Artery / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology / Q000534:rehabilitation*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D005996:Nitroglycerin; D009765:Obesity / Q000150:complications / Q000534:rehabilitation*; D012867:Skin / Q000098:blood supply*; D015431:Weight Loss
chemical_list: D005996:Nitroglycerin