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

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.

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.

Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) μg/ml] and Type 2 diabetes [12.94 (± 2.61)] μg/ml, compared with control subjects [11.83 (± 2.85) μg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (β = 0.32, 0.007), homeostasis model assessment-insulin resistance (β = 0.33, P = 0.01) and HDL (β = -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 (β = -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% (50 μg/ml), 28.4% (100 μg/ml) HDL; P < 0.05)], compared with the control samples.

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.