The dual behavior of heat shock protein 70 and asymmetric dimethylarginine in relation to serum CRP levels in type 2 diabetes

Background: Experimental evidence suggests that heat shock proteins (HSP) and asymmetric dimethylarginine (ADMA) are induced in the state of chronic inflammation and stress conditions. They are both inhibitors of nitric oxide synthase (NOS). The aim of this study was to evaluate the correlation between ADMA and HSP70, in patients with type 2 diabetes with respect to serum levels of C reactive protein (CRP). Methods: We quantified serum HSP70, ADMA and CRP in 80 newly-diagnosed patients with type 2 diabetes plus 80 age-, sex and BMI-matched healthy controls. The patients and controls were also stratified into groups of high and low CRP levels (cut-point: 2.5. mg/ml). Results: Patients with type 2 diabetes had significantly higher serum HSP70 (0.52 [0.51-0.66] vs. 0.27 [0.26-0.36], p < 0.001), ADMA (0.86 [0.81-0.92] vs. 0.72 [0.71-0.85], p < 0.05) and CRP (2.9 [1.7-3.4] vs. 1.6[1.2-2.3], p < 0.05) compared with healthy controls. Serum HSP70 and ADMA levels were significantly correlated in patients with high CRP levels (r = 0.89, p < 0.01), whereas there were no correlation in patients with low CRP (r = - 0.37, p = 0.07) and controls. This correlation was significant (r = 0.77, p < 0.001) in patients with high CRP and also in patients with low CRP levels (r = - 0.51, p < 0.05), after multiple adjustments for LDL and HDL levels. Discussion: We showed that, in a state of high inflammation; serum levels of ADMA parallel the HSP70 levels. However in low inflammation, they are negatively correlated. The duality in HSP70 and ADMA correlation may be related to the duality of NOS function in low and high CRP levels.