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.
AuthorsS Pek, S Tavintharan, K Woon, J Niyati, S C Lim, C F Sum
JournalDiabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 30 Issue 9 Pg. 1067-74 (Sep 2013) ISSN: 1464-5491 [Electronic] England
PMID23600479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.
Chemical References
  • Eye Proteins
  • Lipoproteins, HDL
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • 3T3-L1 Cells
  • Adipocytes, White (metabolism, secretion)
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Body Mass Index
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 (blood, complications, metabolism)
  • Eye Proteins (blood, secretion)
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin Resistance
  • Lipoproteins, HDL (blood, metabolism)
  • Male
  • Mice
  • Middle Aged
  • Nerve Growth Factors (blood, secretion)
  • Overweight (complications)
  • Prediabetic State (blood, complications, metabolism)
  • Prospective Studies
  • Serpins (blood, secretion)
  • Young Adult

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