Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein

作者：Pek S; Tavintharan S^*; Woon K; Niyati J; Lim S C; Sum C F

来源：Diabetic Medicine, 2013, 30(9): 1067-1074.

DOI：10.1111/dme.12198

Aims To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin.
Methods We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis.
Results Mean (+/- sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (+/- 3.06) g/ml] and Type 2 diabetes [12.94 (+/- 2.61)] g/ml, compared with control subjects [11.83 (+/- 2.85) g/ml (P=0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (=0.32, 0.007), homeostasis model assessment-insulin resistance (=0.33, P=0.01) and HDL (= -0.24, P=0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (= -0.439, P=0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50g/ml), 28.4% (100g/ml) HDL; P<0.05)], compared with the control samples.
Conclusion Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.

• 出版日期2013-9