title: Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein.
abstract: OBJECTIVE
  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) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Unit, Khoo Teck Puat Hospital, Singapore.
authors.forename: S
authors.initials: S
authors.lastname: Pek
authors.forename: S
authors.initials: S
authors.lastname: Tavintharan
authors.forename: K
authors.initials: K
authors.lastname: Woon
authors.forename: J
authors.initials: J
authors.lastname: Niyati
authors.forename: S C
authors.initials: SC
authors.lastname: Lim
authors.forename: C F
authors.initials: CF
authors.lastname: Sum
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000378:metabolism; D005136:Eye Proteins / Q000097:blood* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood* / Q000378:metabolism; D050177:Overweight / Q000150:complications; D011236:Prediabetic State / Q000097:blood* / Q000150:complications / Q000378:metabolism; D011446:Prospective Studies; D015843:Serpins / Q000097:blood* / Q000378:metabolism; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D008075:Lipoproteins, HDL; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor