title: A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.
abstract: OBJECTIVE
  We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM.
  
  
  METHODS
  We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM.
  
  
  RESULTS
  pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis.
  
  
  CONCLUSIONS
  pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.
authors.affiliation: Endocrinology Unit, University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Shareen.Forbes@ed.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Forbes
authors.forename: I F
authors.initials: IF
authors.lastname: Godsland
authors.forename: S D
authors.initials: SD
authors.lastname: Taylor-Robinson
authors.forename: J D
authors.initials: JD
authors.lastname: Bell
authors.forename: E L
authors.initials: EL
authors.lastname: Thomas
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: K H
authors.initials: KH
authors.lastname: Parker
authors.forename: I
authors.initials: I
authors.lastname: Marshall
authors.forename: C D
authors.initials: CD
authors.lastname: Gray
authors.forename: D
authors.initials: D
authors.lastname: Bedford
authors.forename: M
authors.initials: M
authors.lastname: Caslake
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: D G
authors.initials: DG
authors.lastname: Johnston
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D016640:Diabetes, Gestational / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D011247:Pregnancy
chemical_list: D007328:Insulin; D008079:Lipoproteins, VLDL