An inverse association between serum soluble receptor of advanced glycation end products and hyperandrogenism and potential implication in polycystic ovary syndrome patients

Abstract

Background: Studies found that AGE-RAGE system is closely related to insulin resistance and hyperandrogenemia, which are two core pathophysiological processes in polycystic ovary syndrome (PCOS). This study is to investigate the relationship among advanced glycation end-products/soluble receptor of advanced glycation end-products (AGEs/sRAGE) and anthropometric evaluation, homeostatic model assessment-insulin resistance (HOMA-IR), free androgen index (FAI) in reproductive-aged PCOS patients.

Methods: One hundred and forty-eight Chinese women with PCOS were enrolled in this study. Subgroups were divided according to body mass index (BMI), waist circumference (WC), quartile intervals of HOMA-IR and androgen levels. The relationships between AGEs/sRAGE and above clinical markers were assessed by Pearson's correlation analyses.

Results: Serum AGEs showed a gradually increased tendency with BMI and WC. It reached statistical significant between the normal weight group (BMI < 24 kg/m²) and the obesity group (BMI ≥ 28 kg/m²) . The sRAGE levels gradually decreased with increasing BMI, WC, HOMA-IR and FAI respectively. Furthermore, the differences between each group were statistical significant. The correlation analysis showed a positive correlation between BMI and serum AGEs levels. On the contrary, the sRAGE levels showed significantly inverse correlations with BMI, WC, HOMA-IR and FAI. The optimal point of sRAGE for the presence of insulin resistance was 704.097 pg/ml by ROC curve analysis.

Conclusions: Along with the body fat accumulation, the serum levels of AGEs were increased, whereas, the serum levels of sRAGE were reduced in obese PCOS patients. The serum levels of sRAGE, which is a decoy receptor, dramatically decreased in the patients with more severe insulin resistant states and higher FAI, which might be a potential biomarker and a promising therapeutic target in the treatment of PCOS, especially in obese subjects.

Keywords: AGEs; Hyperandrogenism; Insulin resistance; Obesity; PCOS; sRAGE.

Fig. 1

The levels of AGEs and sRAGE in different groups were divided according to anthropometric parameters. Data are mean ± SE. AGEs, advanced glycation end products. sRAGE, soluble receptor of AGEs. BMI, body mass index. WC, waist circumference. a and b represent the levels of serum AGEs and sRAGE in different groups were divided according to BMI. NW, the normal weight group (BMI <24 kg/m², n = 53). OW, the overweight group (24 ≤ BMI < 28 kg/m², n = 50). OB, the obesity group (BMI ≥ 28 kg/m², n = 45). P value for analysis of variance for differences between groups: * < 0.05 compared with NW, ** < 0.01 compared with NW. # < 0.05 compared with OW, ## < 0.01 compared with OW. c and d represent the levels of serum AGEs and sRAGE in different groups were divided according to WC. non AO, non-abdominal obese group (WC ≤85 cm, n = 67). OA, abdominal obese group (WC >85 cm, n = 81). P value for analysis of variance for differences between groups: * < 0.05, ** < 0.01

Fig. 2

Results of ELISA for AGEs and sRAGE in the quartile intervals groups. Data are mean ± SE. AGEs, advanced glycation end products. sRAGE, soluble receptor of AGEs. HOMA-IR, homeostatic model assessment-insulin resistance. TT, total testosterone. FAI, free androgen index. a and b represent the levels of serum AGEs and sRAGE in the four HOMA-IR groups. H1 (HOMA-IR <2.49, n = 37), H2 (2.49 ≤ HOMA-IR < 3.92, n = 37), H2 (3.92 ≤ HOMA-IR < 5.88, n = 37), H4 (HOMA-IR ≥ 5.88, n = 37). P value for analysis of variance for differences between groups: * < 0.05 compared with H1, ** < 0.01 compared with H1. c and d represent the levels of serum AGEs and sRAGE in the four TT groups. T1 (TT < 1.22 nmol/L, n = 37), T2 (1.22 nmol/L ≤ TT < 2.09 nmol/L, n = 37), T3 (2.09 nmol/L ≤ TT < 2.69 nmol/L, n = 37), T4 (TT ≥ 2.69 nmol/L, n = 37). e and f represent the levels of serum AGEs and sRAGE in the four FAI groups. F1 (FAI < 3.41, n = 37), F2 (3.41 ≤ FAI < 6.73, n = 37), F3 (6.73 ≤ FAI < 10.59, n = 37), F4 (FAI ≥ 10.59, n = 37). P value for analysis of variance for differences between groups: * < 0.05 compared with F1. # < 0.05 compared with F2

Fig. 3

Correlations between AGEs/sRAGE and other endocrinological parameters. AGEs, advanced glycation end products. sRAGE, soluble receptor of AGEs. BMI, body mass index. WC, waist circumference. HOMA-IR, homeostatic model assessment-insulin resistance. FAI, free androgen index. a represents the correlation between the AGEs and BMI. b, c, d, e represent the correlation between sRAGE and BMI, WC, HOMA-IR and FAI respectively

Fig. 4

ROC curve analysis of sRAGE cut-off points in patients with PCOS