The Impact Of Diabetes To Oxidative Stress And Treatment Outcomes Of Pulmonary Tuberculosis

Objective:Despite the substantial progress in global control tuberculosis,the global burden of tuberculosis remains high.As the prevalence of diabetes increased rapidly in developing country,the association between diabetes and tuberculosis reappears in related field.Recently,Erythrocytes are the most numerous blood cells and rich in oxygen and unsaturated lipids,which makes erythrocytes the most vulnerable cells to oxidative damage by free radicals.However,there is little report of the level of oxidative stress of erythrocyte membrane in patients suffered from both diabetes and tuberculosis(PTB-DM)at present.B-vitamins,especially vitamin B1,B2 and niacin,as the critical coenzyme of many metabolic approaches,play very important roles in metabolism.But the study in vivo levels of water soluble vitamins in PTB-DM patients is rarely reported.Therefore,this study aims to analysis the effect of hyperglycemia on oxidative stress in tuberculosis patients by observing the levels of antioxidant enzymes and oxidative stress products on erythrocytes(membranes)in PTB-DM patients and simple tuberculosis patients(PTB)and the effect of hyperglycemia on nutritional status of tuberculosis patients by detecting the content of water-soluble vitamins in vivo.We also investigated the impact of diabetes on tuberculosis treatment outcome by cumulative meta-analysis.Methods: Our study consists of two hospital based case-control analyses in a Chest Hospital from November 2015 to A?gust 2016.The first one carried out in 45 cases(patients with pulmonary tuberculosis and diabetes mellitus,PTB-DM)and 45 controls(patients with simple pulmonary tuberculosis,PTB).Cases and controls were matched by gender and age.The concentrations of glutathione(GSH),malondialdehyde(MDA)and reactive oxygen species(ROS)in erythrocytes were measured by using colorimetric method,thiobarbituric acid(TBA)and florescent probe separately.We detected the activities of superoxide dismutase(SOD)in erythrocytes and the fluidity of erythrocyte membranes by using hydroxylamine and fluorescent polarization,respectively.The activities of Na+-K+-ATP enzymes were detected by phosphorus determination and the concentration of F2-isoprostanes(8-epi-PGF2?)in erythrocyte membrane was measured by ELISA.Furthermore,the second case-control analysis included 45 case subjects(PTB-DM)and 138 control subjects(PTB)and all subjects were randomly selected and completed three-days 24-h dietary recalls questionnaires.We also collected their urine samples to assessed the intake of water-soluble vitamins.The concentrations of thiamine,riboflavin and N'-methylnicotinamide in urine were detected by fluorospectrophotometer(F4500,Japan).We also investigated the impact of diabetes on tuberculosis treatment outcome using cumulative meta-analysis.Results: The concentration of GSH and the activity of SOD in erythrocytes of PTB-DM group were 6.53 mg GSH/g Hb and 14.15KU/g Hb,respectively.The values were markedly lower in PTB-DM group than those in the PTB group(P<0.05).The activity of Na+-K+-ATP enzymes was 7.10U/ml in PTB-DM group,which was significantly lower than in PTB group.The values of concentrations of F2-isoprostanes showed no significant difference between two groups(P>0.05).Compared with the PTB group,concentration of ROS and MDA in PTB-DM group increased significant(P<0.05)which were 170.95nmol/mg Hb and 0.589nmol/mg Hb respectively and the fluidity of erythrocyte membrane was decreased in PTB-DM group than in the PTB group(P<0.05).The degree of polarization and microviscosity of erythrocyte membrane were 0.154 and 0.900 respectively.The contents of water soluble vitamin B1,B2 and niacin in the PTB-DM group were far lower than those in the PTB group(118.82?g/g vs 89.70?g/g;18.92?g/g vs 11.91?g/g;0.293mg/g vs 0.084mg/g,P<0.05).Only intake of niacin in PTB group was in good condition that arrived over 80% of the recommended intake.The intakes of vitamin B1,B2 in both groups were in poor conditions which didn't arrive 80% of the recommended intake.The correlation analysis showed that there was no correlation between body nutrient status and dietary intakes of water-soluble vitamins.The cumulative meta-analysis showed that diabetes is the risk factor of the treatment outcomes of pulmonary tuberculosis including 2-3 month sputum smear positive(OR=1.71),failure(OR=1.96),death(OR=1.83),relapse(OR=1.97)and relapse into dr?g-resistant tuberculosis(OR=1.5).Conclusion: Hyperglycemia has an effect on the level of oxidative stress of erythrocyte(membranes)and water-soluble vitamin nutrition status in tuberculosis patients.Hyperglycemia can increase the content of oxidation products such as ROS and MDA in the erythrocytes(membranes),decrease the activities of antioxidant enzymes such as SOD and Na+-K+-ATP enzymes,the concentrations of GSH and the fluidity of erythrocyte membrane in PTB patients.The nutrient status of water soluble vitamins such as vitamin B1,B2 and niacin in PTB-DM patients were far poorer than those in the PTB patients.There was a problem of insufficient intake of water soluble vitamins in both two groups and diabetes is a risk factor of the outcome of tuberculosis.