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

Aims/hypothesis 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/interpretation 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

Plasma markers of inflammation and hemostatic and endothelial activity in naturally overweight and obese dogs

“…In addition the soluble form of urokinase PAR, suPAR, was decreased in dogs with weight excess ( p  = 0.002). These findings disagree with other authors that investigated the effect of human obesity on the fibrinolytic system, where increased levels of suPAR was found [44, 45]. Further studies should be performed to determine the reason for these divergences in the behaviour of suPAR in canine and human obesity.…”

Urokinase plasminogen activator receptor and its soluble form in common biopsy-proven kidney diseases and in staging of diabetic nephropathy

“…Moreover, higher suPAR increased the risk and rate development of type 2 DM in non-smoking overweight persons [18,19]. However, our results showed suPAR in type 2 DM without DN did not significantly increase as compared with healthy subjects.…”

Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus

“…Higher suPAR concentrations at baseline have been associated with incident type 2 diabetes in prospective analyses1415. In manifest diabetes, suPAR was associated with diabetes-related complications in a cross-sectional analysis16.…”