title: Discordant effects of rosiglitazone on novel inflammatory biomarkers.
abstract: BACKGROUND
  Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP).
  
  
  METHODS
  Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo.
  
  
  RESULTS
  Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046).
  
  
  CONCLUSIONS
  Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.
authors.affiliation: The Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Elan
authors.initials: E
authors.lastname: Gada
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Owens
authors.forename: M Odette
authors.initials: MO
authors.lastname: Gore
authors.forename: Raphael
authors.initials: R
authors.lastname: See
authors.forename: Shuaib M
authors.initials: SM
authors.lastname: Abdullah
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Anand
authors.initials: A
authors.lastname: Rohatgi
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D017127:Glycation End Products, Advanced / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D053259:Lymphotoxin beta Receptor / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced*; D010865:Pilot Projects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D053259:Lymphotoxin beta Receptor; C491878:PGLYRP1 protein, human; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein