title: Proinflammatory cytokines, adiponectin, and increased risk of primary cardiovascular events in diabetic patients with or without renal dysfunction: results from the ESTHER study.
abstract: OBJECTIVE
  Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events.
  
  
  METHODS
  In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years.
  
  
  RESULTS
  During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12-3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87-2.51], P [trend] = 0.04 for MIF). Adiponectin levels were associated with cardiovascular events in the total population (1.48 [1.01-2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08-3.57], P [trend] = 0.02).
  
  
  CONCLUSIONS
  In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population.
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors: Ben
authors: B
authors: Schöttker
authors: Christian
authors: C
authors: Herder
authors: Dietrich
authors: D
authors: Rothenbacher
authors: Michael
authors: M
authors: Roden
authors: Hubert
authors: H
authors: Kolb
authors: Heiko
authors: H
authors: Müller
authors: Hermann
authors: H
authors: Brenner
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D016207:Cytokines / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models
chemical_list: D052242:Adiponectin; D016207:Cytokines; D020382:Interleukin-18; D015850:Interleukin-6; D020738:Leptin; D008263:Macrophage Migration-Inhibitory Factors; D002097:C-Reactive Protein
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