title: Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.
abstract: OBJECTIVE
  Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals.
  
  
  METHODS
  We studied two prospective cohorts: the Framingham Offspring Study (n = 2,023) and the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study (n = 887) cohorts. Insulin resistance was estimated by HOMA-insulin resistance (HOMA-IR). We used logistic regression analysis to test the association between adiponectin and incident type 2 diabetes overall and in insulin-resistant vs insulin-sensitive individuals (defined by ≥ vs <75th percentile of HOMA-IR).
  
  
  RESULTS
  At baseline, Framingham's participants were 60 ± 9 years old and 56% were women; KORA's participants were 63 ± 5 years old and 49% were women. Type 2 diabetes incidence was 5.4% over 6.5 years (n = 109) in Framingham and 10.5% over 8 years (n = 93) in KORA. Lower adiponectin levels were associated with type 2 diabetes incidence in both cohorts. In insulin-resistant individuals, lower adiponectin levels were associated with higher risk of type 2 diabetes incidence (OR 1.60 [95% CI 1.10-2.31] per SD decrease in Framingham, p = 0.01; and OR 2.34 [95% CI 1.16-4.73] in KORA, p = 0.02); while this was not observed in insulin-sensitive individuals (OR 1.10 [95% CI 0.73-1.67] in Framingham, p = 0.64; and OR 1.34 [95%CI: 0.88-2.03] in KORA, p = 0.18).
  
  
  CONCLUSIONS
  We conclude that lower adiponectin levels are associated with higher risk of type 2 diabetes in insulin-resistant but not in insulin-sensitive individuals. This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: M-F
authors.initials: MF
authors.lastname: Hivert
authors.forename: L M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: P
authors.initials: P
authors.lastname: Shrader
authors.forename: C S
authors.initials: CS
authors.lastname: Fox
authors.forename: D M
authors.initials: DM
authors.lastname: Nathan
authors.forename: R B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: P W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: B
authors.initials: B
authors.lastname: Kowall
authors.forename: C
authors.initials: C
authors.lastname: Herder
authors.forename: C
authors.initials: C
authors.lastname: Meisinger
authors.forename: B
authors.initials: B
authors.lastname: Thorand
authors.forename: W
authors.initials: W
authors.lastname: Rathmann
authors.forename: J B
authors.initials: JB
authors.lastname: Meigs
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D052242:Adiponectin