title: The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men.
abstract: OBJECTIVE
  To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort.
  
  
  METHODS
  The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new-onset diabetes (P < 0.0001).
  
  
  RESULTS
  New-onset diabetes (n = 182) was associated with increased soluble urokinase plasminogen activator receptor levels (P = 0.013). Among 699 middle-aged (41 and 51 years) and 564 older (61 and 71 years) non-smokers, participants in the upper soluble urokinase plasminogen activator receptor quartile had a sex- and age-adjusted relative risk of 6.01 (95% CI 2.17-16.6, P < 0.0006) and relative risk of 3.25 (95% CI 1.51-6.98, P = 0.0025), respectively, for new-onset diabetes compared with participants in the lowest quartile. This relationship remained significant after additional adjustments for C-reactive protein and leukocytes or fasting glucose and insulin or BMI (P < 0.05). The soluble urokinase plasminogen activator receptor was not related to incident diabetes among smokers (P ≥ 0.85).
  
  
  CONCLUSIONS
  In these explorative analyses, the soluble urokinase plasminogen activator receptor associated independently with incident diabetes in non-smokers, supporting an immune origin of Type 2 diabetes. Competing disease risk may explain lack of association among smokers.
authors: Clinical Research Centre, Copenhagen University, Denmark. sbhau@dadlnet.dk
authors: S B
authors: SB
authors: Haugaard
authors: O
authors: O
authors: Andersen
authors: T W
authors: TW
authors: Hansen
authors: J
authors: J
authors: Eugen-Olsen
authors: A
authors: A
authors: Linneberg
authors: S
authors: S
authors: Madsbad
authors: M H
authors: MH
authors: Olsen
authors: T
authors: T
authors: Jørgensen
authors: K
authors: K
authors: Borch-Johnsen
authors: J
authors: J
authors: Jeppesen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood* / Q000276:immunology; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D055293:Receptors, Urokinase Plasminogen Activator