Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians.
Several studies have shown that humoral markers of inflammation and endothelial dysfunction are predictive of macrovascular events, and correlated with indirect measures of adiposity and insulin action, thus providing a possible link between obesity, insulin resistance and atherosclerosis. We examined the relationship between humoral markers of inflammation and endothelial dysfunction and direct measures of adiposity and insulin action in Pima Indians, a population with a very high prevalence of obesity and insulin resistance, but a relatively low propensity for atherosclerotic disease. Fasting plasma concentrations of the inflammatory markers C-reactive protein (CRP), secretory phospholipase A2 (sPLA2) and soluble intercellular adhesion molecule-1 (sICAM-1) and of the endothelial markers E-selectin and von Willebrand factor (vWF) were measured in 32 non-diabetic Pima Indians (18 M/14 F, age 27+/-1 years) in whom percent body fat and insulin-stimulated glucose disposal (M) were assessed by DEXA and a hyperinsulinemic clamp, respectively. CRP, sPLA2, and sICAM-1 were all positively correlated with percent body fat (r=0.71, 0.57, and 0.51, all P<0.01). E-selectin and vWF were not correlated with percent body fat, but were negatively correlated with M (r= -0.65 and -0.46, both P<0.001) and positively correlated with CRP (r=0.46, and 0.33, both P<0.05). These findings indicate that humoral markers of inflammation increase with increasing adiposity in Pima Indians whereas humoral markers of endothelial dysfunction increase primarily in proportion to the degree of insulin resistance and inflammation. Thus, obesity and insulin resistance appear to be associated with low-grade inflammation and endothelial dysfunction, respectively, even in an obesity- and diabetes-prone population with relatively low propensity for atherosclerosis.
Weyer
Christian
C
Clinical Diabetes and Nutrition Section, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 N 16th Street Rm. 5-41, Phoenix, AZ 85016, USA. cweyer@amylin.com
Yudkin
John S
JS
Stehouwer
Coen D A
CD
Schalkwijk
Casper G
CG
Pratley
Richard E
RE
Tataranni
P Antonio
PA
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D001824:Body Constitution; D002097:C-Reactive Protein / Q000032:analysis; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D054501:Group II Phospholipases A2; D006801:Humans; D007198:Indians, North American; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D019040:E-Selectin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2