title: Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes.
abstract: OBJECTIVE
  Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.
  
  
  METHODS
  CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26-47 years, BMI: 24.3-36.3 kg/m(2)) and 12 controls (age: 22-40 years, BMI: 30.1-37.0 kg/m(2))]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.
  
  
  RESULTS
  Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2-352.7) vs. 115.5 (60.5-188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3-0.6) vs. 0.8 (0.5-1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).
  
  
  CONCLUSIONS
  The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.
authors.affiliation: Divisions of Metabolic & Vascular Health and Reproduction, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sivakumar
authors.forename: Muhammad F
authors.initials: MF
authors.lastname: Bari
authors.forename: Manu
authors.initials: M
authors.lastname: Vatish
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016640:Diabetes, Gestational / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors