Serum levels of interleukin 1 beta and interleukin 1 receptor antagonist in patients with diabetes mellitus. Associations with microvascular complications

ABSTRACT

To better understand the potential association of serum levels of interleukin- I beta [IL-1B] and interleukin-1 receptor antagonist [IL-1ra] with diabetic rnicroangiopathy, serum concentrations of IL-1B and IL-1ra were determined in 42 patients with diabetes mellitus [22 non Insulin dependent diabetes mellitus [NIDDM] and 20 insulin dependent diabetes mellitus [IDDM]] presenting with varying degrees of diabetic status and late complications. They were compared with 26 age and sex matched healthy subjects. Our results revealed that the concentrations of IL-1B and IL-1ra were elevated in diabetic patients versus control [Mean +/- SE 0.9 +/- 0.25pg /ml for IL-1B and 752.8 +/- 53.7pg / ml for IL-1ra in diabetics vs 0.08 +/- 0.04pg /ml for IL-1B and 446.6 +/- 40.5pg /ml for IL-1ra in the control, P = 0.01 and P< 0.0001 respectively]. Patients with diabetic retinopathy [n = 16] had the highest concentrations of serum IL-1B compared to those with neuropathy [n = 14] and to those with uncomplicated diabetes [n = 12] [Mean +/- SE 1.78 +/- 0.54pg /ml vs 0.37 +/- 0.32pg /ml and 0.35 +/- 0.16 pg /ml respectively, P = 0.05] IL-1ra levels were the highest In patients with diabetic neuropathy compared to those with retinopathy and uncomplicated diabetics [Mean +/- SE 905.9 +/- 95.2pg /ml vs 749.9 +/- 93.9pg /ml and 578.02 +/- 61.8pg/ml respectively. P<0.05]. Patients with proliferative diabetic retinopathy [n = 10] had significantly higher levels of IL-1B compared to those with non proliferative retinopathy [n= 6] [Mean +/- SE 2.7 +/- 0.71pg /ml vs 0.23 +/- 0.15pg /ml, P< 0.01]. IL-1ra / IL-1B ratio was lowest in patients with diabetic retinopathy especially the prolifertive type and highest in those with neuropathy with uncomplicated diabetics having intermediate values comparable to that of the control [P>0.01], Analyzing pooled data from diabetic patients, a weak negative correlation was found between IL-1B and IL-1ra [r = - 0.22, P> 0.05]. Interstirigly IL-lB was significantly correlated with HDL-cholesterol whereas IL-1ra was significantly correlated with serum triglycerides. IL-1ra/IL-1B ratio was significantly correlated with serum total cholesterol and HDL cholesterol. [r= 0.36 r = 0.38, r = 0.35 and r =-0.34 respectively]. Serum levels of IL-B and IL-1ra are elevated in diabetic patients with and without microangiopathy reflecting ongoing inflammation and macrophage endothelial cell activation. Elevated levels of IL-1B and decreased IL-1ra/IL-1B ratio point more to proliferative retinopathy whereas high levels of IL-1ra and IL-1ra/IL-1B ratio may give an idea about the presence of neuropathy