title: Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study.
abstract: OBJECTIVE
  Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study.
  
  
  METHODS
  Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants. Total microvascular disease was defined as the presence of any nephropathy, retinopathy, neuropathy and/or microvascular amputation. The relationship between FGF21 levels and microvascular disease was assessed by multivariable logistic regression.
  
  
  RESULTS
  Higher baseline FGF21 levels were found in patients with baseline total microvascular disease (p<0.001). The association remained significant after adjusting for potential confounding factors (OR [95% CI] 1.13 [1.08, 1.19] per SD increase in log e -transformed FGF21 levels, p<0.001). Of 6465 patients without baseline total microvascular disease, 1517 developed new on-study total microvascular disease over 5 years of follow-up. Higher baseline FGF21 levels were associated with a higher risk of new on-study total microvascular disease after adjusting for potential confounding factors (OR [95% CI] 1.09 [1.02, 1.16] per SD increase in log e -transformed FGF21 levels, p=0.01). Addition of FGF21 levels in a model of new on-study total microvascular disease with established risk factors significantly, but modestly, increased the integrated discrimination improvement and the net reclassification improvement (both p < 0.01).
  
  
  CONCLUSIONS
  Higher baseline FGF21 levels are seen in patients with type 2 diabetes and established microvascular disease, and predict the future development of new microvascular disease.
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, NSW, 2052, Australia, oklws@yahoo.com.hk.
authors.forename: Kwok-Leung
authors.initials: KL
authors.lastname: Ong
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Januszewski
authors.forename: Rachel
authors.initials: R
authors.lastname: O'Connell
authors.forename: Luke
authors.initials: L
authors.lastname: Buizen
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: David R
authors.initials: DR
authors.lastname: Sullivan
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Russell S
authors.initials: RS
authors.lastname: Scott
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control; D048909:Diabetes Complications / Q000097:blood* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D011345:Fenofibrate