Blood Glutathione Peroxidase Activity in Relation with the Risk of Cardiovascular Diseases in Obese Women

Abstract

Objective: Oxidative stress plays a role in obesity-related diseases. We hypothesize that abnormalities of the glutathione system are associated with the initial phase leading to development of cardiometabolic abnormalities such as cardiovascular diseases and type 2 diabetes in apparently healthy obese women. By measuring different glutathione parameters, we expect to find a dichotomy that can discriminate between obese women who have such sub-clinical abnormalities. Subjects: This is a cross-sectional analysis in 59 postmenopausal obese women. Total blood glutathione, glutathione peroxidase (GPx) and glutathione reductase activity, blood lipids, apolipoprotein B-100 (apoB), fasting and area under the curve (AUC) for glycemia and insulinemia during an oral glucose tolerance test, insulin sensitivity measurement and indices, serum inflammatory markers and carotid intima-media thickness (CIMT, by magnetic resonance imaging) were measured. Results: Blood GPx activity had a bimodal distribution. Subjects were then divided into two groups according to their GPx activity (cut-off: 2.0 nmol/min/mg protein, P<0.01). Age and BMI were similar between the groups. Women with higher GPx activity had 13% more apoB (P=0.02), 10% higher glycemia AUC (P=0.04), hepatic insulin resistance (28% and 25% higher HOMA and liver insulin resistance index values, P<0.04) and increased CIMT by 8-13% (P=0.013) without evidence of inflammation, changes in blood lipids, and fasting glycemia and insulinemia. Conclusion: Results suggest that a modification in the glutathione system is associated with insulin resistance and increased intima-media thickness, both of which are associated with cardiovascular disease risk. Blood GPx activity may be a parameter contributing in the identification of sub-clinical but clinically relevant asymptomatic cardiometabolic abnormalities in obese women.