1. ^*Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, Minnesota
2. ^†Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio
3. ^‡Department of Gastroenterology and PathoBiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio

Correspondence: Frank González Address correspondence to Frank González, Mayo Clinic, Department of Obstetrics and Gynecology, Charlton 3-117, 200 First Street SW, Rochester, MN 55905. E-mail: gonzalez.frank@mayo.edu

^**The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1 October 2006; Accepted 19 February 2007.

Abstract

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-1 (IL-1) 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 B (NFB) 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-1 (- 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 NFB (9.4 7.3 vs. - 23.5 13.5% ). Truncal fat was positively correlated with the MNC-derived IL-6 response ( = 0.58, p < 0.05) and intra-nuclear NFB ( = 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.