title: Longitudinal association of C-reactive protein and Haemoglobin A1c over 13 years: the European Prospective Investigation into Cancer--Norfolk study.
abstract: BACKGROUND
  Type-2 diabetes is associated with systemic inflammation and higher C-reactive protein (CRP) levels. However, the longitudinal association of CRP and haemoglobin-A1c (HbA1c) has not been described in large prospective studies. Understanding such associations may shed light on the role of inflammation in development of type-2 diabetes and its complications such as cardiovascular diseases.
  
  
  METHODS
  EPIC-Norfolk is a cohort study of men and women aged 40-79 years at time of recruitment (1993-1997). Serum CRP (mg/l) was measured using a high-sensitivity assay at baseline and 13-years follow-up. HbA1c (%) was measured at baseline, 4, and 13 years. Participants were excluded if they were diagnosed with diabetes or were taking diabetes medication. Data on at least one measurement of CRP and HbA1c was available for 14228 participants (55 % of the cohort).
  
  
  RESULTS
  In the cross-sectional analysis of baseline data, a 1-SD higher loge-CRP (about three-fold higher CRP) was associated with 0.06 (95 % CI 0.04, 0.08) higher HbA1c (%) adjusted for potential confounders. In longitudinal analysis using multivariable linear mixed models, change in CRP over 13 years was to a similar extent positively associated with increase in HbA1c, such that 1-SD higher longitudinal change in loge-CRP was associated with 0.04 (95 % CI 0.02, 0.05) increase in HbA1c.
  
  
  CONCLUSIONS
  In this study we found longitudinal observational evidence suggesting that increase in systemic inflammation is associated with an increase in HbA1c and thus systemic inflammation may have a role in development of type-2 diabetes and its complications.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. s.ahmadi-abhari@ucl.ac.uk.|Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK. s.ahmadi-abhari@ucl.ac.uk.
authors.forename: Sara
authors.initials: S
authors.lastname: Ahmadi-Abhari
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. skk22@medschl.cam.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaptoge
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. robert.luben@phpc.cam.ac.uk.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.affiliation: Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Sciences, Cambridge, UK. nick.wareham@mrc-epid.cam.ac.uk.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. kk101@medschl.cam.ac.uk.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism*; D005060:Europe; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human