title: Plasma copeptin and the risk of diabetes mellitus.
abstract: BACKGROUND
  Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited.
  
  
  RESULTS
  We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001).
  
  
  CONCLUSIONS
  Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
authors.affiliation: Department of Clinical Sciences, Lund University, Clinical Research Center, Entrance 72, Bldg 91, Floor 12, Malmö University Hospital, SE 20502 Malmö, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Enhörning
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Peter M
authors.initials: PM
authors.lastname: Nilsson
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Göran
authors.initials: G
authors.lastname: Berglund
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Eero
authors.initials: E
authors.lastname: Lindholm
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Valeria
authors.initials: V
authors.lastname: Lyssenko
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D015995:Prevalence; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D001786:Blood Glucose; D006020:Glycopeptides; D007328:Insulin; C048197:copeptins