title: Associations of insulin resistance, inflammation and liver synthetic function with very low-density lipoprotein: The Cardiovascular Health Study.
abstract: BACKGROUND
  Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation.
  
  
  METHODS
  We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study.
  
  
  RESULTS
  Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size.
  
  
  CONCLUSIONS
  Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115. Electronic address: zgjiang@bidmc.harvard.edu.
authors.forename: Z Gordon
authors.initials: ZG
authors.lastname: Jiang
authors.affiliation: Division of Nephrology, University of Washington, Seattle, WA 98195.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115.
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lai
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, MA 02115.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT 05405.
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA 02115.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D005167:Factor VII / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D012307:Risk Factors; D012959:Socioeconomic Factors
chemical_list: D008079:Lipoproteins, VLDL; D005167:Factor VII; D002097:C-Reactive Protein
keywords: Insulin resistance; Liver synthetic function; Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); Very low-density lipoprotein (VLDL)