title: Adiponectin trajectories before type 2 diabetes diagnosis: Whitehall II study.
abstract: OBJECTIVE
  The role of adiponectin in the natural history of diabetes is not well characterized. We set out to characterize prediagnosis trajectories of adiponectin in individuals who develop type 2 diabetes.
  
  
  METHODS
  In a case-cohort study (335 incident diabetes case and 2,474 noncase subjects) nested in the Whitehall II study, serum adiponectin was measured up to three times per participant (1991-1993, 1997-1999, and 2003-2004). Multilevel models adjusted for age and ethnicity were fitted to assess 13-year trajectories of log-transformed adiponectin preceding diabetes diagnosis or a randomly selected time point during follow-up (year(0)) based on 755/5,095 (case/noncase) person-examinations.
  
  
  RESULTS
  Adiponectin levels were lower in diabetes case than in noncase subjects (median 7,141 [interquartile range 5,187-10,304] vs. 8,818 [6,535-12,369] ng/mL at baseline, P < 0.0001). Control subjects showed a modest decline in adiponectin throughout follow-up (0.3% per year, P < 0.0001) at higher levels in women than in men (difference at year(0): 5,358 ng/mL, P < 0.0001). Female case and early-onset case (age at diagnosis <52 years) subjects had a steeper decline than control subjects (slope difference -1.1% per year, P = 0.001 in females, -1.6% per year in early-onset case subjects, P = 0.034). In men, adiponectin slopes for case and noncase subjects were parallel. The slope differences by diabetes onset were largely attenuated after adjustment for changes in obesity, whereas the sex-specific slope differences were independent of obesity.
  
  
  CONCLUSIONS
  Lower adiponectin levels were observed already a decade before the diagnosis of diabetes. The marked sex difference in trajectories suggests that sex-specific mechanisms affect the association between adiponectin levels and diabetes development.
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, UK. a.tabak@ucl.ac.uk
authors.forename: Adam G
authors.initials: AG
authors.lastname: Tabák
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brunner
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shipley
authors.forename: Markus
authors.initials: M
authors.lastname: Jokela
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D052242:Adiponectin; D001786:Blood Glucose