Oxidized LDL Is Associated With Metabolic Syndrome Traits Independently of Central Obesity and Insulin Resistance

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.

Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome

“…This results in an expression compatible with resistance to thyroid hormone. Thyroid stimuli still increase, although insufficiently, the uncoupled thermogenic oxidative processes, which can be observed as an increase of oxidative stress in metabolic syndrome (36). A sustained compensatory TSH stimulus could also explain, in part, the recently reported association of metabolic syndrome, insulin resistance, and diabetes with thyroid enlargement, thyroid nodules, and thyroid cancer (37).…”

Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype

“…The synergistic effects of the MetS components may lead to cardiovascular disease as children with obesity become young adults [5][6][7], and this may be announced by an increased OS biomarkers level [7,8]. OS may play a causative role in the development of obesity and co-morbidities [9][10][11][12]. The possible contributors to OS in obesity include hyperglycemia, elevated lipid levels, chronic low grade inflammation with increased circulating cytokines produced by visceral adipose depots as well as myokines production by skeletal muscles, in those with low physical activity level and higher weigh to carry, endothelial dysfunction, unhealthy diets [7][8][9][10][11][12].…”

“…Evidence has demonstrated that OS levels are elevated in adults with obesity [12], but pediatric data in this area are limited. In our sample, Ox-LDL level was measured as a marker of oxidative damage and it was found to be elevated in children with obesity, particularly in those with visceral adiposity.…”

“…The increased oxidative environment contributes to a chronic inflammatory condition in the body and builds primary risk factors for the development of several diseases such as diabetes and has cardiovascular complications [7,8]. On the other hand, the increased OS in obesity and metabolic disorders causes progression and sustenance of inflammatory conditions upregulating redox signaling pathways and altering gene expression of inflammatory markers, kicking off a vicious circle [9][10][11][12].…”

“…Recent data suggest that increased OS in adipose tissue is an early instigator of MetS and that the redox state in adipose tissue is potentially a useful therapeutic target for the obesity-associated MetS [11,12]. Data on the association between Ox-LDL levels and MetS have been reported in adults [11,12]; however, in pediatric ages data are very limited [14].…”