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Hyperglycemia Alters Tumor Necrosis Factor- Release from Mononuclear Cells in Women with Polycystic Ovary Syndrome

Departments of Reproductive Biology (F.G., J.M., N.S.R.) and Medicine (J.P.K.), Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109

Address all correspondence and requests for reprints to: Frank González, MetroHealth Medical Center, Department of Obstetrics and Gynecology, Hamann S4-44, 2500 MetroHealth Drive, Cleveland, Ohio 44109. E-mail: fgonzalez{at}metrohealth.org.

Context: Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation.

Objective: The purpose of this study was to determine the effects of hyperglycemia on lipopolysaccharide (LPS)-stimulated TNF release from mononuclear cells (MNC) in PCOS.

Design: The study was designed as a prospective controlled study.

Setting: The study was carried out at an academic medical center.

Patients: Sixteen reproductive age women with PCOS (eight lean, eight obese) and 14 age-matched controls (eight lean, six obese) participated in the study.

Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (IS_OGTT). Percentage of truncal fat was determined by dual-energy absorptiometry. TNF release was measured from MNC cultured in the presence of LPS from blood samples drawn fasting and 2 h after glucose ingestion.

Results: IS_OGTT was lower in women with PCOS compared with controls (3.9 ± 0.4 vs. 6.3 ± 1.0; P < 0.03) and was negatively correlated with percentage of truncal fat (r = 0.56; P < 0.002). Truncal fat was greater in lean women with PCOS compared with lean controls (29.8 ± 2.6 vs. 23.8 ± 2.5%; P < 0.04). The TNF response was different between obese and lean controls (–96.9 ± 21.2 vs. 24.4 ± 21.6 pg/ml; P < 0.03) and obese and lean women with PCOS (–94.1 ± 34.5 vs. 30.4 ± 17.6 pg/ml; P < 0.002). Fasting plasma C-reactive protein was elevated (P < 0.003) in obese PCOS and obese controls compared with lean controls.

Conclusion: An increase in abdominal adiposity and increased TNF release from MNC after hyperglycemia may contribute to insulin resistance in lean PCOS patients. In contrast, obese PCOS patients have more profound chronic inflammation, and thus may have LPS tolerance that protects them from relatively mild excursions in blood glucose.

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