Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome.
OBJECTIVE
Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end-products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes.


METHODS
We investigated serum AGE levels in 29 young women with PCOS as well as the expression of their receptor, RAGE, in circulating monocytes and compared them levels with 22 healthy control women.


RESULTS
Women with PCOS had higher levels of serum AGE proteins compared to healthy individuals (9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001), and increased RAGE expression was observed in monocytes of PCOS women compared to controls (30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02). A positive correlation was observed between AGE proteins and testosterone (T) levels (r = 0.73, P < 0.0001). The correlation between AGE proteins and T levels remained high (partial correlation coefficient = 0.61, P = 0.0001) after controlling for body mass index (BMI), insulin levels and the area under the curve for glucose (AUCGLU) during an oral glucose tolerance test (OGTT). A positive correlation was also observed between AGE proteins and the free androgen index (FAI) (r = 0.58, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.31, P < 0.02), insulin (r = 0.46, P < 0.001), homeostasis model assessment (HOMA) (r = 0.47, P < 0.0001), AUCGLU (r = 0.52, P < 0.002) and RAGE (r = 0.59, P < 0.01). A negative correlation was observed between AGE proteins and glucose/insulin ratio (GLU/INS) (r = -0.35, P < 0.01), and the quantitative insulin sensitivity check index (QUICKI) (r =-0.50, P < 0.01). In multiple regression analysis T was the only independent predictor of AGE levels (P < 0.0001, b = 0.044) between BMI, insulin, SHBG and AUCGLU (adjusted R2 = 0.59, F = 44.41, P < 0.0001).


CONCLUSIONS
These data clearly demonstrate, for the first time, that PCOS women without overt hyperglycaemia have increased AGE levels and elevated RAGE expression when compared with controls.
Diamanti-Kandarakis
Evanthia
E
First Department of Internal Medicine, Endocrine Section, Aretaieion Hospital, University of Athens Medical School, Athens, Greece. akandara@otenet.gr
Piperi
Christina
C
Kalofoutis
Anastasios
A
Creatsas
George
G
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005947:Glucose; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000097:blood; D012044:Regression Analysis; D012307:Risk Factors; D013739:Testosterone / Q000097:blood
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013739:Testosterone; D005947:Glucose