Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome.
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.
Hamdy
Osama
O
Clinical Research Center, Joslin Diabetes Center, the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA. osama.handy@joslin.harvard.edu
Ledbury
Sarah
S
Mullooly
Cathy
C
Jarema
Catherine
C
Porter
Satoko
S
Ovalle
Kerry
K
Moussa
Amr
A
Caselli
Antonella
A
Caballero
A Enrique
AE
Economides
Panayiotis A
PA
Veves
Aristidis
A
Horton
Edward S
ES
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
D005996:Nitroglycerin