title: Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis.
abstract: OBJECTIVE
  The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA.
  
  
  METHODS
  The coronary calcium score, homeostatic model assessment for insulin resistance (HOMA-IR) index, and serum adipocytokine (leptin, adiponectin, resistin, and visfatin) concentrations were determined in 169 patients with RA. The independent effect of each adipocytokine on insulin resistance according to the HOMA-IR index and on coronary artery calcification determined by electron beam computed tomography was assessed in models adjusted for age, race, sex, body mass index (BMI), traditional cardiovascular risk factors, and inflammation mediators. In addition, an interaction analysis was performed to evaluate whether the effect of the HOMA-IR index on the coronary calcium score is moderated by adipocytokines.
  
  
  RESULTS
  Increased concentrations of leptin were associated with a higher HOMA-IR index, even after adjustment for age, race, sex, BMI, traditional cardiovascular risk factors, and inflammation mediators (P < 0.001), but concentrations of visfatin (P = 0.06), adiponectin (P = 0.55), and resistin (P = 0.98) showed no association with the HOMA-IR index. None of the adipocytokines was independently associated with the coronary calcium score (all P > 0.05). Serum leptin concentrations showed a significant interaction with the HOMA-IR index (P for multivariate interaction = 0.02). Increasing leptin concentrations attenuated the increased risk of coronary calcification related to insulin resistance. Serum concentrations of the other adipocytokines showed no significant interactions with the HOMA-IR index (each P > 0.05).
  
  
  CONCLUSIONS
  Leptin is associated with insulin resistance in patients with RA but, paradoxically, attenuates the effects of insulin resistance on coronary calcification.
authors.affiliation: Vanderbilt University, Nashville, Tennessee 37232-6602, USA.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Rho
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Solus
authors.forename: Paolo
authors.initials: P
authors.lastname: Raggi
authors.forename: Annette
authors.initials: A
authors.lastname: Oeser
authors.forename: Tebeb
authors.initials: T
authors.lastname: Gebretsadik
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000453:epidemiology*; D002114:Calcinosis / Q000097:blood / Q000453:epidemiology; D002118:Calcium / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D015995:Prevalence; D052243:Resistin / Q000097:blood; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D018836:Inflammation Mediators; D020738:Leptin; C499624:RETN protein, human; D052243:Resistin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D002118:Calcium