Disordered glycemic control in women with type 2 diabetes is associated with increased TNF receptor-2 levels.

Abstract

Evidence implicates tumor necrosis factor (TNF) in the pathophysiology of Type 2 Diabetes (T2D) through unclear mechanisms. We hypothesized that disordered glycemic control leads to TNF activation and increases in soluble-TNF (sTNF) and its receptors-1 (sTNFR1) and -2 (sTNFR2). We characterized 265 T2D and non-diabetic Latin American subjects and assessed the relationship between the TNF system and fasting plasma glucose (FPG), hemoglobin-A1C (A1C), insulin (FPI), C-peptide and HOMA-Beta. sTNF and sTNFR2 but not sTNFR1 levels were higher in T2D than non-diabetics (P<0.0001). In T2D, sTNFR2 was associated with A1C and C-peptide (R2=0.354, b=0.504, P<0.0001; b=0.167, P=0.049). Also, T2D patients with disordered glycemic control had increased sTNFR2 levels that correlated with FPG (Rho:0.393, P<0.001), A1C (Rho:0.451, P<0.001) and HOMA-Beta (Rho:-0.308, P=0.005); events not observed in T2D patients with adequate glycemic control. Furthermore, sex-based comparative analyses of T2D patients showed that women compared to men had higher sTNFR2 levels (P=0.017) that correlated with FPG, A1C, FPI and HOMA-Beta. Disordered glycemic control is associated with sTNF and sTNFR2. sTNFR2 levels were higher in T2D women than men. Thus, increased sTNFR2 levels may be an important biomarker for disordered glucose and inflammatory complications in T2D patients and women in particular.