Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance

Authors: HURTADO-ROCA, YAMILEE - National Center For Cardiovascular Research(CNIC); BUENO, HECTOR - National Center For Cardiovascular Research(CNIC); FERNANDEZ-ORTIZ, ANTONIO - National Center For Cardiovascular Research(CNIC); ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; IBANEZ, BORJA - National Center For Cardiovascular Research(CNIC); FUSTER, VALENTIN - National Center For Cardiovascular Research(CNIC); RODRIQUEZ-ARTALEJO, FERNANDO - Centro De Investigacion Biomedica En Red (CIBER)-Epidemiología Y Salud Pública; LACLAUSTRA, MARTIN - National Center For Cardiovascular Research(CNIC)

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/23/2016
Publication Date: 2/1/2017
Citation: Hurtado-Roca, Y., Bueno, H., Fernandez-Ortiz, A., Ordovas, J., Ibanez, B., Fuster, V., Rodriquez-Artalejo, F., Laclaustra, M. 2017. Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance. Diabetes. doi: 10.2337/db16-0933.

Interpretive Summary: Low-density lipoprotein (LDL) cholesterol (popularly known as "bad" cholesterol) is a risk factor for cardiovascular disease. When people have bad diets and lifestyles, smoke, and have some disease conditions, oxidative stress occurs, and LDL is oxidized. Both oxidative stress overall and oxidized LDL are believed to contribute to development of metabolic syndrome, an accumulation of cardiovascular risk factors. It is also suspected that obesity contributes to the oxidation of these particles. It may also have some relation to the development of insulin resistance, a marker of type 2 diabetes. Therefore, we investigated these interrelationships using 3,987 subjects participating in the Progression of Early Subclinical Atherosclerosis (PESA) Study. Our results indicate that oxidized LDL concentrations were associated with the presence of metabolic syndrome independently of central obesity and insulin resistance. Therefore, LDL oxidation may be the central mechanism of the development of metabolic syndrome in parallel with insulin resistance and could be a clinically relevant predictor of the development of metabolic syndrome, a major risk factor for cardiovascular diseases.

Technical Abstract: This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baseline data from 3,987 subjects without diabetes in the Progression of Early Subclinical Atherosclerosis (PESA) Study. For the second, third, and fourth ox-LDL quartiles versus the first, the odds ratios (95% CI) for MS were 0.84 (0.52, 1.36), 1.47 (0.95, 2.32), and 2.57 (1.66, 4.04) (P < 0.001 for trend) once adjusted for age, sex, smoking, LDL-cholesterol, BMI, waist circumference, and HOMA-insulin resistance (HOMA-IR). Results showing the same trend were found for all MS components except glucose concentration. Ox-LDL mediated 13.9% of the association of waist circumference with triglycerides and only 1-3% of the association with HDL-cholesterol, blood pressure, and insulin concentration. HOMA-IR did not mediate the association between ox-LDL and MS components. This study found higher ox-LDL concentrations were associated with MS and its components independently of central obesity and insulin resistance. Ox-LDL may reflect core mechanisms through which MS components develop and progress in parallel with insulin resistance and could be a clinically relevant predictor of MS development.