Glycemic Control and Oxidative Stress Markers and their relationship with the Thioredoxin Interacting Protein (TXNIP) gene in Type 2 Diabetic patients

Abstract

Objective: To investigate the relationship between oxidative stress and biochemical parameters and the expression of TXNIP, IL-6, IL-1 beta and TNF-alpha in peripheral mononuclear cells (PMCs) from type-2 diabetic patients.

Methods: We studied 60 males: 20 normal-weight type-2 diabetic patients (NW), 20 obese diabetic patients (OB) and 20 controls (C). Biochemical and oxidative stress parameters were evaluated. PMCs were isolated and total RNA was extracted in order to determine the expression of TXNIP, IL-6, IL-1 beta and TNF-alpha by qRT-PCR.

Results: OB had higher weight, BMI and abdominal circumference (One way ANOVA, p<0.0001). NW had higher fasting glycemia (One way ANOVA, p=0.0034) however OR had higher HbA1c (One way ANOVA, p<0.0001). OR also had higher hsCRP (One way ANOVA, p=0.0158). MARS and AGES were elevated in both NW and OR (One way ANOVA, p<0.0001 and p=0.0008, respectively). Compared to OR and C participants, the expression of TXNIP was significantly higher in NW (Kruskal Wallis, p=0.0074); IL-1 beta, IL-6 and TNF-alpha transcripts were higher in NW and OR (Kruskal Wallis, p<0.0001, for all). In NW patients, the expression of TXNIP was positively correlated with fasting glycemia and AGES and negatively correlated with HOMA-beta (r=0.72; r=0.59; r=-0.44, respectively, for all p<0.05), in OB there was correlation only with 8-Isoprostanes (r=0.42, p=0.046).

Conclusions: Our results suggest that fasting glycemic control, independent of adiposity and nutritional status, represents a risk factor for p-cell dysfunction, increases oxidative stress markers and it is related with an elevation of TXNIP expression.