Insufficient glycemic control increases nuclear factor-κB binding activity in peripheral blood mononuclear cells isolated from patients with type I diabetes

OBJECTIVE - The redox-sensitive transcription factor nuclear factor-kappa B (NF-kappa B) is believed to contribute to late diabetic complications. It is unknown whether NF-kappa B is influenced by glycemic control. RESEARCH DESIGN AND METHODS - To determine whether NF-kappa B is activated in patients with insufficient glycemic control (HbA(1c) > 10%), we developed a tissue culture-independent electrophoretic mobility shift assay (EMSA)-based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells (PBMCs). We included 43 patients with type 1 diabetes in this cross-sectional study; 10 of those received the antioxidant thioctic acid (600 mg/day p.o.) for 2 weeks. RESULTS - Monocytes of patients with HbA(1c) levels > 10% demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA(1c) levels of 6-8%, The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity. CONCLUSIONS - Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kappa B activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid significantly lowered the extent of NF-kappa B binding activity.