title: The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation: effect modification by smoking and body weight status.
abstract: OBJECTIVE
  Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status.
  
  
  METHODS
  The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body weight status and suPAR were tested.
  
  
  RESULTS
  During a 3-year follow-up (599 incident diabetes cases), there was a 48% overall increase in the odds of developing type 2 diabetes per twofold increase in suPAR (p = 0.006). This association was modified by body weight status in overweight, but not in obese individuals (OR 2.36, 95% CI 1.48, 3.76 in overweight group), and by smoking status (OR 2.05, 95% CI 1.20, 3.51 in non-smokers). After adjustment for other diabetes risk factors, the association between suPAR and type 2 diabetes was attenuated in the whole sample and among non-smokers, but remained robust among overweight participants.
  
  
  CONCLUSIONS
  suPAR may be a good novel biomarker for systemic sub-clinical inflammation and immune activation linked to incident type 2 diabetes risk in overweight individuals and non-smokers. The observed interactions with adiposity and smoking should be investigated further.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. alex.heraclides@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Heraclides
authors.forename: T M
authors.initials: TM
authors.lastname: Jensen
authors.forename: S S
authors.initials: SS
authors.lastname: Rasmussen
authors.forename: J
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: S B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: K
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: A
authors.initials: A
authors.lastname: Sandbæk
authors.forename: T
authors.initials: T
authors.lastname: Lauritzen
authors.forename: D R
authors.initials: DR
authors.lastname: Witte
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator