Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia

Objective: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive‐age women. Research Methods and Procedures: Seven obese and 6 age‐matched lean women (20 to 39 years of age) underwent a 2‐hour 75‐g oral glucose tolerance test. The release of interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) from MNCs cultured in the presence of lipopolysaccharide (LPS) was measured after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Reactive oxygen species (ROS) generation and intra‐nuclear nuclear factor κB (NFκB) from MNCs were quantified from the same blood samples. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). Total body fat and truncal fat were determined by DXA. Results: Obese women had a higher (p < 0.03) total body fat (42.2 ± 1.1 vs. 27.7 ± 2.0%), truncal fat (42.1 ± 1.2 vs. 22.3 ± 2.4%), and HOMA‐IR (3.3 ± 0.5 vs. 1.8 ± 0.2). LPS‐stimulated IL‐6 release from MNCs was suppressed during hyperglycemia in lean subjects (1884 ± 495 vs. 638 ± 435 pg/mL, p < 0.05) but not in obese women (1184 ± 387 vs. 1403 ± 498 pg/mL). There was a difference (p < 0.05) between groups in the hyperglycemia‐induced MNC‐mediated release of IL‐6 (?1196 ± 475 vs. 219 ± 175 pg/mL) and IL‐1β (?79 ± 43 vs. 17 ± 12 pg/mL). In addition, the obese group exhibited increased (p < 0.05) MNC‐derived ROS generation (39.3 ± 9.9 vs. ?1.0 ± 12.8%) and intra‐nuclear NFκB (9.4 ± 7.3 vs. ?23.5 ± 13.5%). Truncal fat was positively correlated with the MNC‐derived IL‐6 response (ρ = 0.58, p < 0.05) and intra‐nuclear NFκB (ρ = 0.64, p < 0.05). Discussion: These data suggest that obese reproductive‐age women are unable to suppress proatherogenic inflammation during physiological hyperglycemia. Increased adiposity may be a significant contributor to this pro‐inflammatory susceptibility.