title: Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study.
abstract: To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults.
  
  
  
  Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design.
  
  
  
  In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99).
  
  
  
  Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes.
authors.affiliation: Graduate Studies Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. vcluft@hcpa.edu.br.|Food and Nutrition Research Centre, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. vcluft@hcpa.edu.br.
authors.forename: V C
authors.initials: VC
authors.lastname: Luft
authors.affiliation: Graduate Studies Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.|Department of Epidemiology, Chapel Hill, NC, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Duncan
authors.affiliation: Graduate Studies Program in Epidemiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.|Department of Epidemiology, Chapel Hill, NC, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Schmidt
authors.affiliation: Department of Epidemiology, Chapel Hill, NC, USA.|Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Chambless
authors.affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Hoogeveen
authors.affiliation: Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Couper
authors.affiliation: Department of Epidemiology, Chapel Hill, NC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Heiss
mesh_terms: D050197:Atherosclerosis / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000453:epidemiology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000453:epidemiology; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D015994:Incidence; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine