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 TNFα 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. TNFα 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 TNFα 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 TNFα 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.