Inflammation in Response to Glucose Ingestion Is Independent of Excess Abdominal Adiposity in Normal-Weight Women with Polycystic Ovary Syndrome

Context: Inflammation and excess abdominal adiposity (AA) are often present in normal-weight women with polycystic ovary syndrome (PCOS). Objective: We determined the effects of hyperglycemia on nuclear factor-kappa B (NF kappa B) activation in mononuclear cells (MNC) of normal-weight women with PCOS with and without excess AA. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: Fifteen normal-weight, reproductive-age women with PCOS (seven normal AA, eight excess AA) and 16 body composition-matched controls (eight normal AA, eight excess AA) participated in the study. Main Outcome Measures: Body composition was measured by dual-energy absorptiometry. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Activated NF kappa B and the protein content of p65 and inhibitory-kappa B were quantified from MNC, and TNF alpha and C-reactive protein (CRP) were measured in plasma obtained from blood drawn while fasting and 2 h after glucose ingestion. Results: Compared with controls, both PCOS groups exhibited lower ISOGTT, increases in activated NF kappa B and p65 protein, and decreases in inhibitory-kappa B protein. Compared with women with PCOS with excess AA, those with normalAAexhibited higher testosterone levels and lower TNF alpha and CRP levels. For the combined groups, the percent change in NF kappa B activation was negatively correlated with ISOGTT and positively correlated with androgens. TNF alpha and CRP were positively correlated with abdominal fat. Conclusion: In normal-weight women with PCOS, the inflammatory response to glucose ingestion is independent of excess AA. Circulating MNC and excess AA are separate and unique sources of inflammation in this population. (J Clin Endocrinol Metab 97: 4071-4079, 2012)