《结核病与糖尿病共病的治疗管理专家共识》解读

结核病与糖尿病共病的治疗管理一直是临床上的棘手问题,需要结核科与内分泌科医生共同制定治疗方案,共同进行随访管理,才能进一步提高其治愈率和降低死亡率。发表于《中国防痨杂志》2021年第1期的《结核病与糖尿病共病的治疗管理专家共识》就结核病与糖尿病共病治疗管理的常见问题提出了具体处理建议。笔者主要对共识中的共病概念、共病时糖尿病的治疗管理、相关药品不良反应的处理及注意事项等方面作进一步解读,以供中国从事结核病和糖尿病的临床工作者借鉴和参考。     

糖尿病并发结核病的发病率及其临床特征

糖尿病患者是结核病的高危人群,糖尿病患病率的逐年增高已开始影响结核病的流行特征,两病并发率正逐年增高。糖尿病的存在可影响结核病的临床特征,出现一些非典型的临床表现,如结核好发于下肺野、耐药性高及复发率高等。本文综述了近几年糖尿病对结核病流行及临床特征影响的报道,以期引起预防机构和临床医生的重视,更好地进行两病并发的预防与治疗。     

糖尿病并发结核病的发病率及其临床特征

糖尿病患者是结核病的高危人群，糖尿病患病率的逐年增高已开始影响结核病的流行特征，两病并发率正逐年增高。糖尿病的存在可影响结核病的临床特征，出现一些非典型的临床表现，如结核好发于下肺野、耐药性高及复发率高等。本文综述了近几年糖尿病对结核病流行及临床特征影响的报道，以期引起预防机构和临床医生的重视，更好地进行两病并发的预防与治疗。     

世界卫生组织《应对结核病及其共病合作行动框架》解读

在全球范围内,结核病仍然是由单一传染性病原体导致死亡的主要原因之一。主要的结核病共病和与结核病相关的健康危险因素包括人类免疫缺陷病毒感染、酗酒、营养不良、吸烟、糖尿病、精神失常、矽肺和病毒性肝炎。应对结核病患者共病和相关健康危险因素对于终止结核病流行至关重要。为实现这一目标,诊疗、护理和关怀的重点应该放在患者上,而不是具体的疾病上,全球应致力于合作应对结核病及其共病问题。为此,2022年10月,世界卫生组织制定了《应对结核病及其共病合作行动框架》,框架分为5个部分,每部分均列出了有助于推广合作防控结核病及其共病问题的主要行动。笔者就该文件制定的行动框架概要、主要共病和行动原则等进行解读,以供相关专业工作者参考。     

小檗碱对结核病并糖尿病的作用

随着社会生活水平改善，糖尿病发病率有增加趋势，结核并糖尿病是结核病的特殊人群，两病并发率也逐年递增，临床治疗难度大。小檗碱对结核杆菌有抑菌作用，对血糖有调节作用。本文就小檗碱对结核病并精尿病的作用进行综述。     

结核病并发糖尿病治疗管理相关进展

据估算,至2045年全球糖尿病患者可能会增长至7亿例,大约16%的结核病患者会并发糖尿病,结核病并发糖尿病(TB-DM)的双重负担会成为一个重大的全球性公共卫生问题。糖尿病(包括1型和2型)会增加活动性结核病的风险,与单纯结核病患者相比,TB-DM患者的治疗转归更差。糖尿病发病率的增长不但将增加罹患结核病的患病风险,还对结核病的治疗管理构成严重挑战。作者就TB-DM的双向筛查、相互影响、治疗和管理、药品相互作用等内容进行综述。     

精神分裂症合并2型糖尿病的临床研究与分析

精神分裂症与糖尿病共病现象在临床上比较常见,其真正的发生机理还不是很明确。由于两种疾病的相互影响,增加了治疗的困难。为了能够对这一共病现象有更深入的了解,并在治疗效果上取得较好的进展,临床上已经进行了许多相关的研究。特别是近年来的研究结果,在理论和实践两方面都获得了一些很实用的经验。该文主要从精神分裂症合并2型糖尿病的发病率、共病可能的原因、治疗方法与效果、康复管理等方面对近年来临床上的研究结果作一综述。     

糖尿病与抑郁症共病的相关性研究进展

基础和临床研究已发现,抑郁症和2型糖尿病共病发生率高,病情复杂,且增加了临床抑郁症和糖尿病治疗护理的难度,两者间既相互影响,又互为危险因素,但机制目前仍不确定。本文综述了糖尿病与抑郁症共病的可能机制、相互影响及治疗方面的研究进展,旨在突出两者的相关性,为临床个体化诊断及治疗提供理论依据。     

肌少性肥胖与2型糖尿病关系的研究进展

随着全球人口老龄化的加剧和生活方式的改变, 肌少性肥胖与糖尿病共病患者日益增多, 且二者的发病机制密切相关, 两者并存可能导致更多不良结局。本文就肌少性肥胖的诊断标准与流行病学及其与糖尿病的内在联系、共病人群的管理方法等内容进行综述, 旨在为临床提供理论依据与治疗思路。     

糖尿病并发结核病流行病学研究现状

目前糖尿病患病率增加 ,结核病“回潮”(发达国家 )和控制不良 (发展中国家 ) ,导致糖尿病和结核病并发人数逐年增多。糖尿病病人由于代谢紊乱、营养失衡及免疫损伤 ,容易发生结核病 ,其中低龄、男性、1型糖尿病病人发生结核病的危险性更大 ,而且发病后 ,结核病病情较重 ,疗效不佳 ;结核病可使糖尿病病人血糖波动 ,病情恶化。对两病并发应以预防为主 ,包括积极控制糖尿病病人血糖 ,定期进行胸部X线检查、开展预防性治疗 ;对结核病人也应常规监测血糖     

Impact of diabetes on the natural history of tuberculosis

Tuberculosis (TB) is the number one bacterial killer worldwide and the current increase in type 2 diabetes mellitus patients (DM), particularly in countries where TB is also endemic, has led to the re-emerging importance of DM2 as a risk factor for TB. There is an urgent need to implement strategies for TB prevention among the millions of DM patients exposed to Mycobacterium tuberculosis (Mtb) worldwide, but knowledge is limited on how and when DM2 alters the natural history of this infection. In this review we summarize the current epidemiological, clinical and immunologic studies on TB and DM and discuss the clinical and public health implications of these findings. Specifically, we evaluate the mechanisms by which DM patients have a higher risk of Mtb infection and TB development, present with signs and symptoms indicative of a more infectious TB infection, and are more likely to have adverse TB treatment outcomes, including death. Emphasis is placed on type 2 DM given its higher prevalence in contemporary times, but the underlying role of hyperglycemia and of type 1 DM is also discussed.     

Screening patients with Diabetes Mellitus for Tuberculosis in China

Objective There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics. Method Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom‐based enquiry, and those positive to any symptom were referred for TB investigations. Results In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti‐TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in‐house training, special assignment of staff for screening and colocation of services. Conclusion This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient‐related implications.     

Diabetes and tuberculosis in Mexico: results from epidemiological studies

The association between tuberculosis (TB) and type 2 diabetes mellitus (DM2) has been recognized during centuries, and recently, a vast number of studies have evidenced their relationship. Uncontrolled diabetes and a poor glycemic control increase the risk for TB infection. Both diseases are considered chronic diseases; constituting important worldwide health problems. In Mexico, the prevalence of DM2 among TB patients varies, rising levels up to 36%. Several epidemiological studies have been conducted in the country and in the Border States, giving an estimate of the real situation of this comorbidity and in consequence, contributing to improve the diagnosis and follow-up of patients. In this review, we updated the research data on DM2 by means of observational and experimental studies conducted in Mexico in the last 17 years. Results show the continuous increase of TB-DM2 incidence and the need for the establishment of proper control methods acting over this dual axis.     

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Tuberculosis (TB) is known to be fueled by HIV as well as social and economic factors. With progression of the diabetes mellitus (DM) pandemic in countries where TB is also endemic, focus is increasing on the potential links between DM and TB. Despite the magnitude of the DM-TB association woldwide, it is striking how little we know about the underlying biology that promotes this association which is a major concern to public health. In this review we summarize current findings regarding the alterations in the innate and adaptive immune responses of DM patients to Mycobacterium tuberculosis (Mtb). Current findings suggest underperforming innate immunity followed by a hyper-reactive cellular response to Mtb, but the contribution of these altered responses to TB susceptibility or to the more adverse clinical outcomes of TB patients with DM remains unclear. Elucidating the basic mechanisms underlying the higher susceptibility of DM patients to TB should lead to a strategy for stratification of the millions of DM patients worldwide into those with the highest TB risk for targeted TB prevention.     

A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients

Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis). MET enhances the production of mitochondrial reactive oxygen species and facilitates phagosome–lysosome fusion; those mechanism are important in M. tuberculosis elimination. Moreover, MET-associated lactic acidosis (MALA) needs to be considered and the incidence of MALA in patients with type 2 DM–TB coinfection remains unknown. This result contributes much to our understanding about the clinical effect of MET use in type 2 DM–TB coinfection.For the purpose of understanding the MET effect as an adjuvant therapy in TB therapy and insulin simultaneous therapy, an observational clinical study was done in type 2 DM newly TB coinfection outpatients at Surabaya Paru Hospital. Patients were divided into two groups. First group was MET group, in which the patients were given MET accompanying insulin and TB treatment regimens, the golden standard therapy of DM–TB coinfection. MET therapy was given for at least 2 months. Second group was non-MET group, in which the patients were given insulin and TB treatment regimens. The lactate levels in both groups were measured after 2 months.Among 42 participants, there was no case of lactic acidosis during this study period. Data were normally distributed; thus, we continued analysis of the difference using paired T-test with 95% confidence. There was no difference in lactate levels (p = 0.396) after MET therapy compared to non-MET group.In this study involving patients with TB pulmonary diseases, there is neither evidence that MET therapy induced lactic acidosis event nor that it increased lactate blood level. Thus, we concluded that MET use in type 2 DM–TB coinfection did not induce lactic acidosis.     

Clinical features of diabetic patients with pulmonary tuberculosis admitted to a university hospital

Diabetes mellitus (DM) is a risk factor of tuberculosis (TB). We studied the clinical presentation of pulmonary TB among patients with DM in comparison with patients without DM who were admitted into the hospital of the University of the Ryukyus from 2006 to 2010. The clinical data were collected from medical records retrospectively. Ten cases (25%) of hospitalized patients with pulmonary TB had DM. The DM group showed lower Body Mass Index and higher incidence of chronic heart failure and chronic renal failure. The DM group also were more likely to have cavitary lesion, had longer period of hospitalization, and higher mortality. Their causes of deaths were mainly the co-morbidities and associated complications. Further studies are warranted in order to fully elucidate the relationships between pulmonary TB and DM.     

Detrimental association between diabetes and tuberculosis: An unresolved double trouble

Despite significant efforts made to control tuberculosis (TB) through DOTS program, the increasing burden of diabetes mellitus (DM) threatens the progress in reducing TB-related mortality, particularly in developing countries. In recent years, TB-DM comorbidity continues to remain high in countries where DM is on rampant. DM increases the risk of TB, reactivates the dormant TB and worsens the TB treatment outcome. The present review highlights the current findings regarding the prevalence and association of TB-DM comorbidity along with their public health implications. This review will increase the awareness among researchers, policymakers and clinicians, regarding the current scenario of TB-DM association.     

Treatment Options for HIV-Associated Tuberculosis

The vicious interaction between the human immunodeficiency virus (HIV) infection and tuberculosis (TB) pandemics poses special challenges to national control programs and individual physicians. Although recommendations for the treatment of TB in HIV-infected patients do not significantly differ from those for HIV-uninfected patients, the appropriate management of HIV-associated TB is complicated by health system issues, diagnostic difficulties, adherence concerns, overlapping adverse-effect profiles and drug interactions, and the occurrence of paradoxical reactions after the initiation of effective antiretroviral therapy. In this article, recommended treatment strategies and novel approaches to the management of HIV-associated TB are reviewed, including adjuvant treatment and options for treatment simplification. A focused research agenda is proposed in the context of the limitations of the current knowledge framework.     

Screening of patients with tuberculosis for diabetes mellitus in China

Objective There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and this study aimed to assess feasibility and results of screening patients with TB for DM within the routine healthcare setting of six health facilities. Method Agreement on how to screen, monitor and record was reached in May 2011 at a stakeholders’ meeting, and training was carried out for staff in the six facilities in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. Results There were 8886 registered patients with TB. They were first asked whether they had DM. If the answer was no, they were screened with a random blood glucose (RBG) followed by fasting blood glucose (FBG) in those with RBG ≥ 6.1 mm (one facility) or with an initial FBG (five facilities). Those with FBG ≥ 7.0 mm were referred to DM clinics for diagnostic confirmation with a second FBG. Altogether, 1090 (12.4%) patients with DM were identified, of whom 863 (9.7%) had a known diagnosis of DM. Of 8023 patients who needed screening for DM, 7947 (99%) were screened. This resulted in a new diagnosis of DM in 227 patients (2.9% of screened patients), and of these, 226 were enrolled to DM care. In addition, 575 (7.8%) persons had impaired fasting glucose (FBG 6.1 to <7.0 mm ). Prevalence of DM was significantly higher in patients in health facilities serving urban populations (14.0%) than rural populations (10.6%) and higher in hospital patients (13.5%) than those attending TB clinics (8.5%). Conclusion This pilot project shows that it is feasible to screen patients with TB for DM in the routine setting, resulting in a high yield of patients with known and newly diagnosed disease. Free blood tests for glucose measurement and integration of TB and DM services may improve the diagnosis and management of dually affected patients.     

Coprevalence of type 2 diabetes mellitus and tuberculosis in low‐income and middle‐income countries: A systematic review

Increasing coprevalence of diabetes mellitus (DM) and tuberculosis (TB) in low‐income and middle‐income countries (LMICs) indicates a rising threat to the decades of progress made against TB and requires global attention. This systematic review provides a summary of type 2 diabetes and tuberculosis coprevalence in various LMICs. We searched PubMed, Ovid Medline, Embase, and PsychINFO databases for studies that provided estimates of TB‐DM coprevalence in LMICs published between 1990 and 2016. Studies that were non‐English and exclusively conducted in multidrug resistant‐tuberculosis or type 1 diabetes and inpatient settings were excluded. We reviewed 84 studies from 31 countries. There were huge diversity of study designs and diagnostic methods used to estimate coprevalence, and this precluded pooling of the results. Most studies (n = 78) were from small, localized settings. The DM prevalence among TB patients in various LMICs varied from 1.8% to 45%, with the majority (n = 44) between 10% and 30%. The TB prevalence among people with DM ranged from 0.1% to 6.0% with most studies (n = 9) reporting prevalences less than 2%. Coprevalence of TB‐DM was higher than general population prevalence of either diseases in these countries. This study underscores the need for intervention and more focused research on TB DM bidirectional screening programs in low‐income and middle‐income countries as well as integrated chronic disease management.