title: Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study.
abstract: The immune response involved in each phase of type 2 diabetes (T2D) development might be different. We aimed to identify novel inflammatory markers that predict progression from normoglycemia to pre-diabetes, incident T2D and insulin therapy. We used plasma levels of 26 inflammatory markers in 971 subjects from the Rotterdam Study. Among them 17 are novel and 9 previously studied. Cox regression models were built to perform survival analysis.
  
  
  
  During a follow-up of up to 14.7 years (between April 1, 1997, and Jan 1, 2012) 139 cases of pre-diabetes, 110 cases of T2D and 26 cases of insulin initiation were identified. In age and sex adjusted Cox models, IL13 (HR = 0.78), EN-RAGE (1.30), CFH (1.24), IL18 (1.22) and CRP (1.32) were associated with incident pre-diabetes. IL13 (0.62), IL17 (0.75), EN-RAGE (1.25), complement 3 (1.44), IL18 (1.35), TNFRII (1.27), IL1ra (1.24) and CRP (1.64) were associated with incident T2D. In multivariate models, IL13 (0.77), EN-RAGE (1.23) and CRP (1.26) remained associated with pre-diabetes. IL13 (0.67), IL17 (0.76) and CRP (1.32) remained associated with T2D. IL13 (0.55) was the only marker associated with initiation of insulin therapy in diabetics. Various inflammatory markers are associated with progression from normoglycemia to pre-diabetes (IL13, EN-RAGE, CRP), T2D (IL13, IL17, CRP) or insulin therapy start (IL13). Among them, EN-RAGE is a novel inflammatory marker for pre-diabetes, IL17 for incident T2D and IL13 for pre-diabetes, incident T2D and insulin therapy start.
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Adela
authors.initials: A
authors.lastname: Brahimaj
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Symen
authors.initials: S
authors.lastname: Ligthart
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ghanbari
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.|Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Mohammad Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.|Harvard School of Public Health, Boston, MA, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. a.dehghan@erasmusmc.nl.
authors.forename: Abbas
authors.identifier: 0000-0001-6403-016X
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology*; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011236:Prediabetic State / Q000097:blood* / Q000453:epidemiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: EN-RAGE; IL13; IL17; Inflammatory markers; Insulin therapy; Novel; Phase-specific; Pre-diabetes; Type 2 diabetes