title: Impaired non-esterified fatty acid suppression to intravenous glucose during late pregnancy persists postpartum in gestational diabetes: a dominant role for decreased insulin secretion rather than insulin resistance.
abstract: OBJECTIVE
  Non-esterified fatty acids are implicated in the pathogenesis of gestational (GDM) and type 2 diabetes. We examined the relationship between NEFA dynamics, insulin resistance and beta cell dysfunction in women with GDM in late pregnancy and postpartum.
  
  
  METHODS
  A total of 19 Caucasian women with GDM and 19 healthy pregnant women matched for BMI and age underwent an IVGTT in the third trimester and 4 months postpartum, deriving values for insulin sensitivity (SI), insulin secretion (AIRg) and disposition index (DI). NEFA levels were measured serially.
  
  
  RESULTS
  In pregnancy, the GDM women had similar SI but reduced AIRg and DI compared with control subjects. The GDM group demonstrated significantly slower NEFA suppression, which was attributable to the GDM women who required insulin during pregnancy (n=7) and who had markedly reduced AIRg and K(NEFA) (NEFA disappearance constant) compared with their matched controls. In contrast, GDM subjects not requiring insulin (n=12) had similar NEFA suppression curves and AIRg to control subjects. Postpartum, GDM subjects demonstrated reduced SI and DI. The impaired suppression of NEFA persisted postpartum, but again only in the subgroup of GDM subjects who had required insulin during pregnancy. Furthermore, K(NEFA) correlated with AIRg and DI in both states, but not with SI.
  
  
  CONCLUSIONS
  Impaired NEFA suppression occurs in GDM subjects both in late pregnancy and postpartum in response to IVGTT-induced endogenous insulin secretion. The impaired NEFA suppression is present in GDM women with the most severe beta cell dysfunction (who had required insulin during pregnancy) and is related to their insulin secretory dysfunction rather than their reduced SI.
authors.affiliation: Department of Endocrinology and Diabetes, St Vincent's Hospital, Fitzroy, Australia. mclachk@svhm.org.au
authors.forename: K A
authors.initials: KA
authors.lastname: McLachlan
authors.forename: R
authors.initials: R
authors.lastname: Boston
authors.forename: F P
authors.initials: FP
authors.lastname: Alford
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D016640:Diabetes, Gestational / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D049590:Postpartum Period / Q000502:physiology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000502:physiology
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose