title: Copeptin, Insulin Resistance, and Risk of Incident Diabetes in Older Men.
abstract: BACKGROUND
  Prior studies suggested a role for the arginine vasopressin (AVP) system in the pathogenesis of diabetes. Prospective studies on the association between copeptin (the C-terminal fragment of AVP hormone) and incident diabetes are limited.
  
  
  OBJECTIVE
  We have examined the association between plasma copeptin and the risk of incident diabetes in older men.
  
  
  METHODS
  The British Regional Heart Study was a prospective study with an average of 13 years follow-up.
  
  
  METHODS
  General practices in the United Kingdom were studied.
  
  
  METHODS
  Participants were 3226 men aged 60 to 79 years with no prevalent diabetes.
  
  
  RESULTS
  We measured 253 patients with incident diabetes.
  
  
  RESULTS
  Copeptin was positively and significantly associated with renal dysfunction, insulin resistance (homeostasis model assessment of insulin resistance), metabolic risk factors (waist circumference, blood pressure, triglycerides, and liver function), C-reactive protein, tissue plasminogen activator, and von Willebrand factor (endothelial dysfunction) but not with plasma glucose. The risk of incident diabetes was significantly elevated only in men in the top fifth of the copeptin distribution (>6.79 pmol/L), and this risk persisted after adjustment for several diabetes risk factors including metabolic risk factors and C-reactive protein (adjusted hazard ratio in the top fifth vs the rest = 1.78 [95% confidence interval, 1.34-2.37]). Risk was markedly attenuated although it remained significant after further adjustment for homeostasis model assessment of insulin resistance and plasma glucose (adjusted hazard ratio = 1.47 [1.11-1.97]). The increased risk was seen even when the analysis was restricted to men with no chronic kidney disease or to men with no impaired fasting glucose (<6.1 mmol/L).
  
  
  CONCLUSIONS
  Copeptin is associated with a significantly increased risk of diabetes in older men. The association is partly mediated through lower insulin sensitivity. The findings suggest a potential role of the AVP system in diabetes.
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: S Goya
authors.initials: SG
authors.lastname: Wannamethee
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: Olia
authors.initials: O
authors.lastname: Papacosta
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lennon
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
authors.affiliation: Department of Primary Care and Population Health (S.G.W., O.P., L.L.), University College Medical School, Royal Free Campus, London NW3 2PF, United Kingdom; British Heart Foundation Glasgow Cardiovascular Research Centre (P.W., N.S.), Faculty of Medicine, University of Glasgow, G12 8TA Glasgow, United Kingdom; and Department of Community Health Sciences (P.H.W.), St George's, University of London SW17 ORE, London, United Kingdom.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk; D006113:United Kingdom
chemical_list: D006020:Glycopeptides; C048197:copeptins