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Overweight Latino Children and Adolescents Have Marked Endothelial Dysfunction and Subclinical Vascular Inflammation in Association With Excess Body Fat and Insulin Resistance

¹ Joslin Diabetes Center, Clinical Research Center, Harvard Medical School, Boston, Massachusetts
² Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Niterüi, Rio de Janeiro, Brazil

Address correspondence and reprint requests to A. Enrique Caballero, MD, Latino Diabetes Initiative, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: enrique.caballero{at}joslin.harvard.edu

OBJECTIVE—We measured plasma markers of endothelial dysfunction, vascular inflammation, and pro-coagulation in obese Hispanic/Latino children and adolescents with normal glucose tolerance and determined their relationship to body composition and indexes of glucose and lipid metabolism.

RESEARCH DESIGN AND METHODS—A total of 38 lean or obese Hispanic children and adolescents (10–18 years of age) were selected. The overweight group (n = 21) had a BMI >85th percentile for their age and sex, and the lean group (n = 17) had a BMI between the 25th and 50th percentiles. Studies included an oral glucose tolerance test, measurements of plasma glucose and lipids, several markers of endothelial function and inflammation, and determination of body composition by dual X-ray absorptiometry.

RESULTS—The obese group had higher systolic blood pressure and plasma triglycerides and was more insulin resistant than the lean group. The obese group also had higher plasma soluble intercellular adhesion molecule (259.5 ± 60.0 vs. 223.2 ± 47.5 ng/ml, P = 0.047), tumor necrosis factor- (2.57 ± 1.1 vs. 1.74 ± 0.6 pg/ml, P = 0.008), high-sensitivity C-reactive protein (2.0 vs. 0.13 mg/l, P < 0.0001), plasminogen-activated inhibitor-1 (47.0 ± 35.7 vs. 12.0 ± 5.2 ng/ml, P < 0.0001), tissue plasminogen activator (6.1 ± 1.9 vs. 4.1 ± 0.8 ng/ml, P = 0.001), and white blood cell count (6.9 vs. 5.3 x 10³, P = 0.031) and lower levels of adiponectin (8.7 ± 3.3 vs. 12.6 ± 5.2 µg/ml, P = 0.022). No significant differences were observed for soluble vascular cell adhesion molecule or interleukin-6.

CONCLUSIONS—Overweight Hispanic children and adolescents with normal glucose tolerance exhibit increased plasma markers of endothelial dysfunction and subclinical inflammation in association with obesity and insulin resistance. These abnormalities may predispose them to the development of type 2 diabetes and cardiovascular disease.

Abbreviations: AUC, area under the curve • CIR, corrected insulin response • CRP, C-reactive protein • HOMA, homeostasis model assessment • HOMA β-cell, HOMA of β-cell function • HOMA-IR, HOMA of insulin resistance • hs-CRP, high-sensitivity CRP • IL, interleukin • ISI, insulin sensitivity index • JDC, Joslin Diabetes Center • OGTT, oral glucose tolerance test • PAI-1, plasminogen activator inhibitor-1 • sICAM, soluble intercellular adhesion molecule • sVCAM, soluble vascular cell adhesion molecule • TNF-, tumor necrosis factor • tPA, tissue plasminogen activator • WBC, white blood cell count

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