Study On The Risk Factors Of Drug Induced Liver Injury In Patients With Concurrent Tuberculosis And Diabetes And The Relationship Between Glycolipid Metabolism And Immuno-inflammatory Level

Objective:Tuberculosis?TB?is still a serious global public health problem.First-line antituberculosis drugs are prone to side effects in the treatment process,among which liver injury is the most common and serious side effect.In recent years,the dual burden of pulmonary tuberculosis?PTB?and diabetes mellitus?DM?has attracted more and more attention.The risk of active tuberculosis in diabetic patients increases due to the decrease of immune function.Previous studies have shown that the main influencing factors of liver injury in TB treatment are age,gender,nutritional status,combined diseases,the use of liver protective drugs,the severity of tuberculosis,drinking,smoking,physical activity,etc.,but there is no report on the influencing factors of liver injury in PTB-DM treatment at home and abroad.PTB-DM patients are prone to abnormal glucose and lipid metabolism.When TB patients with DM,the level of immune inflammation increased.However,there are few reports about the relationship between glycolipid metabolism and immune inflammatory level in PTB-DM patients at home and abroad.Therefore,based on the above situation,the first chapter of this study,based on the clinical data of PTB-DM patients in Qingdao,describes and analyzes the occurrence and influencing factors of liver injury,and provides theoretical basis for the development of prevention and control of liver injury.The second chapter explores the characteristics of glycolipid metabolism and the relationship between glycolipid metabolism and the level of immune inflammation in PTB-DM population.Methods:In the first chapter of this study,a prospective cohort study was carried out to collect baseline exposure data such as general demographic characteristics,blood glucose control,life style,behavior,habits,nutritional status,dietary intake and other baseline exposure data of patients diagnosed as diabetes complicated with pulmonary tuberculosis and hospitalized in Qingdao chest Hospital from October 2017 to March 2019,follow-up to collect the situation of liver injury.Univariate and multivariate Cox proportional hazard regression analysis was used to determine the risk factors for liver injury.In chapter 2,a cross-sectional study was adopted to compare the glucose and lipid metabolism characteristics of the two groups of patients who were admitted to Qingdao Chest Hospital at the same time and were diagnosed as pulmonary tuberculosis and admitted to hospital.According to whether they were combined with diabetes,they were divided into simple pulmonary tuberculosis group?PTB?and pulmonary tuberculosis with diabetes mellitus?PTB-DM?.According to the fasting blood glucose level,the PTB-DM group was divided into the high blood glucose group and the low blood glucose group,and the abnormal blood lipid group and the normal blood lipid group were divided into the abnormal blood lipid group and the normal blood lipid group,to compare the differences of immune inflammatory levels.Correlation analysis was used to explore the relationship between blood glucose,blood lipids and immune inflammatory correlation indexes,and multiple linear regression analysis was used to judge the relationship between glucose and lipid metabolism characteristics and immune inflammatory correlation indexes.Results:In the first chapter,458 patients with pulmonary tuberculosis and diabetes were included,of whom 53 suffered from liver injury and incidence rate of liver injury was11.6%.After adjusting for poor blood sugar control,smoking index,physical activity,types of liver protection agents and anemia,the risk of liver injury was 3.46 times higher among drinkers than among nondrinkers?HR=3.46,95%CI:1.14-10.53,P=0.029?,the risk of liver injury in emaciated patients was 3.84 times higher than that in other patients?HR=4.84,95%CI:1.43-16.31,P=0.011?,compared with patients with moderate or adequate dietary diversity,patients with insufficient dietary diversity had a 3.14-fold increased risk of liver injury?HR=4.14,95%CI:1.02-16.86,P=0.047?.Poor blood glucose control and heavy smoking may be related to the increased risk of liver injury?P=0.097 and P=0.056?,which has marginal statistical significance.In the second chapter,779 TB patients were included,including 482 in PTB group and 297 in PTB-DM group.The proportion of abnormal glucose and lipid metabolism in PTB-DM group was significantly higher than that in PTB group.Multiple linear regression showed that the level of CD₄⁺T cells in female patients was 104.35/?L higher than that in male patients[B:104.35,95%CI:?0.04208.66?,P=0.050],while the level of CD₄⁺T cells in patientswith simple abnormal blood glucose was 119.09/?L lower than that in other patients[B:-119.09,95%CI:?-224.84,-13.35?,P=0.028],the level of CD₈⁺T cells in patients with abnormal glycolipid metabolism was 118.59/?L higher than other patients[B:118.59,95%CI:?9.03,228.15?,P=0.034],the level of serum IgA was 341.33mg/d L higher than other patients[B:341.33,95%CI:?101.48,581.18?,P=0.005],the level of IL-6 was74.24pg/mL higher than other patients[B:74.24,95%CI:?8.18,140.30?,P=0.028].Conclusion:In this study,the incidence of liver injury in patients with pulmonary tuberculosis complicated with diabetes was 11.6%.Alcohol consumption,weight loss and lack of dietary diversity were independent risk factors for liver injury in patients with tuberculosis complicated with diabetes.Poor blood glucose control and heavy smoking may be the risk factors for liver injury;the abnormal glucose and lipid metabolism in patients with tuberculosis and diabetes mellitus is related to the impairment of inflammatory response,cellular and humoral immune function.