Hyperglycemia alters tumor necrosis factor-alpha release from mononuclear cells in women with polycystic ovary syndrome.
BACKGROUND
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 TNFalpha release from mononuclear cells (MNC) in PCOS.


METHODS
The study was designed as a prospective controlled study.


METHODS
The study was carried out at an academic medical center.


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


METHODS
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. TNFalpha 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 TNFalpha 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.


CONCLUSIONS
An increase in abdominal adiposity and increased TNFalpha 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.
MetroHealth Medical Center, Department of Obstetrics and Gynecology, Hamann S4-44, 2500 MetroHealth Drive, Cleveland, Ohio 44109, USA. fgonzalez@metrohealth.org
Frank
F
González
Judi
J
Minium
Neal S
NS
Rote
John P
JP
Kirwan
D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism*; D007333:Insulin Resistance; D009000:Monocytes / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein