Serum level of pigment epithelium-derived factor in different glucose tolerance state

Abstract

Objective To investigate serum levels of pigment epithelium-derived factor (PEDF) in subjects with different glucose tolerance and its influencing factors. Methods A total of 571 Chinese participants, who underwent 75 g oral glucose tolerance test (OGTT) in the Department of Endocrinology of Nanjing Drum Tower Hospital from June 2010 to February 2013 were divided into three groups: normal glucose tolerance (NGT), impaired glucose regulation (IGR) and type 2 diabetes mellitus (T2DM) group. Circulating PEDF levels and metabolic profiles were assessed in the participants. Serum estradiol levels were determined in females. 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and homeostasis model assessment of β-cell function(HOMA-β) were used to evaluate insulin sensitivity and β-cell function. Analysis of variance was used for data analysis. The relationship between PEDF and other metabolic parameters was analyzed by using Spearman correlation analysis and multiple stepwise analysis. Results There were 186 participants in NGT group, 216 in IGR group and 169 in T2DM group. The mean age was (50±14) years. No significant differences were observed in the male and female ration (χ2=3.138,P= 0.208) and body mass index (BMI) (F=2.410,P=0.091) among the three groups. Compared with that in control group(8.5 (7.1, 10.7) mg/L), serum PEDF level was significantly higher in IGR group(10(8, 11) mg/L) and T2DM group(10(8, 12) mg/L) (F=6.911,P=0.010). Serum PEDF level in males was significantly higher than that in females ((10(8, 12) vs 9(7, 11) mg/L,t=3.001,P=0.003). Spearman correlation analysis showed that PEDF levels was positively associated with BMI, waist circumference, waist-to-hip ratio, fasting and 2 h postprandial glucose (r=0.311, 0.302, 0.124, 0.188, allP<0.001). Multiple stepwise regression analysis revealed that PEDF was associated with 1/HOMA-IR, waist circumference, diastolic blood pressure and systolic blood pressure after the adjustment for age and gender (t=-4.927, 4.532, 3.701, -2.265, allP<0.05). Subjects with a higher tertile of PEDF level exhibited a higher level of BMI, waist circumference, fasting and 2 h postprandial glucose, fasting and 2 h postprandial insulin and HOMA-β than those in patients with the lower tertile of PEDF level(F=8.214-34.461, all P<0.01). Furthermore, serum estradiol level was negatively associated with PEDF (r=- 0.216,P=0.013). Multiple stepwise regression analysis showed that decreasing estradiol was an independent risk factor of increasing PEDF in post-menopause females (β =-0.213,P= 0.009). Conclusions PEDF concentration is significantly elevated in patients with IGR. Decreased estradiol level is an independent risk factor for the elevated PEDF, which can contribute to the occurrence of T2DM in post-menopause females. Key words: Diabetes mellitus, type 2; Pigment epithelium-derived factor; Impaired glucose regulation; Estradiol