title: Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy.
abstract: OBJECTIVE
  Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies.
  
  
  METHODS
  We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case-control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic-euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6-9) and body fat distribution by MRI in late pregnancy (n = 10/group).
  
  
  RESULTS
  Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04).
  
  
  CONCLUSIONS
  Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.
authors.affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK. Shareen.Forbes@ed.ac.uk.|Endocrinology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Shareen.Forbes@ed.ac.uk.
authors.forename: Shareen
authors.initials: S
authors.lastname: Forbes
authors.affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Barr
authors.affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.|Endocrinology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Semple
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Calum
authors.initials: C
authors.lastname: Gray
authors.affiliation: Endocrinology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Denison
authors.affiliation: Endocrinology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Tommy's Centre for Fetal and Maternal Health, MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000097:blood* / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Insulin resistance; MRI; Pregnancy; Stable isotope studies; Very severe obesity