Combined analysis of biochemical parameters in serum and differential gene expression in circulating leukocytes may serve as an ex vivo monitoring system to estimate risk factors for complications in Diabetes mellitus

Summary.

Objective: Oxidative stress plays a crucial role in the development of complications in Diabetes mellitus (DM). Individual sensitivity against stress, however, varies among DM-patients and results, therefore, in differential severity of consequent complications. To allow more complex interpretation of a delicate antioxidant/free radicals balance and its effect on cellular functions in individual DM-patients, we analysed a correlation between total antioxidant status (TAS), antioxidant gap (AtxGap), level of free radicals (FR), routine clinical biochemical parameters in blood and differential gene expression in circulating leukocytes of DM-patients versus non-diabetic individuals.

Results and conclusions: Positive correlation was found between TAS and creatinine (p=0.05), AtxGap and iron (p=0.025), and between AtxGap and anti-streptolysin O (p=0.025). Whereas no correlation was found between FR and any of the routine clinical parameters tested, a negative correlation was observed between AtxGap and glucose content (p=0.025) and between AtxGap and γ-glutamyltransferase (p=0.05). An increased content of FR was shown to influence significantly an expression of selected stress responsible genes in leukocytes. Transcription levels of NF-kappaB, XRCC1 and 90-kDa heat-shock protein A were increased in all DM-patients compared to non-diabetic individuals. In contrast, an expression of XIAP and cytochrome P450 reductase was up-regulated in patients with decreased levels of both FR and TAS and increased body mass index. This differential expression of the stress responsible genes might be further considered as a potential risk factor for diverse DM-complications helping also in reliable monitoring of supplemental antioxidant therapy and more complex interpretation of delicate antioxidant/free radicals balance.