Authors: S Forbes I F Godsland S D TaylorRobinson J D Bell E L Thomas N Patel G Hamilton K H Parker I Marshall C D Gray D Bedford M Caslake B R Walker D G Johnston
Publish Date: 2013/06/13
Volume: 56, Issue: 9, Pages: 2021-2033
Abstract
We have previously reported a high prevalence of nonalcoholic 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 pGDMWe analysed data from a cohort of 234 women 114 with pGDM and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasounddiagnosed 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 pGDMpGDM was associated with increased IHCL p = 004 after adjustment for adiposity Independently of IHCL pGDM was associated with a lower IVGTT disposition index p = 002 and acute insulin response to glucose pGDM+/NAFLD− 50 lower pGDM+/NAFLD+ 36 lower effect of pGDM p = 003 increased VLDL apoB pool size pGDM+/NAFLD− 31fold higher pGDM+/NAFLD+ 12fold higher effect of pGDM p = 002 and at borderline significance p = 005 increased rate of VLDL apoB synthesispGDM 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
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