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      Helicobacter pylori Infection is Associated with Occurrence of Proteinuria in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis Translated title: 2型糖尿病患者出现蛋白尿和幽门螺旋杆菌感染的联 系:荟萃分析

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          Type 2 diabetes (T2DM) patients are susceptible to Helicobacter pylori (HP), and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients; however, this view remains controversial. This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients. In addition, we hope to provide some recommendations to readers in clinical or related fields.


          Our meta-analysis was conducted with the methodology of the Cochrane Collaboration. Search strategies were formulated by relevant professionals. Case–control studies that compared the occurrence of proteinuria in T2DM patients with and without HP infection were involved in our meta-analysis. Relevant English or Chinese studies were searched on online databases before 2018, including PubMed, the Cochrane library, Medline, Google Scholar, the China National Infrastructure, and Wanfang database. The search strategies were “diabetic proteinuria, diabetic microalbuminuria, diabetic albuminuria, diabetic kidney disease, diabetic renal dysfunction, diabetic renal disease, diabetic nephropathy, diabetic complications, and diabetic mellitus, combined with HP.” The quality of these involved articles was separately assessed by two investigators using the Newcastle–Ottawa Scale (NOS). Odds ratios ( ORs) and associated 95% confidence intervals ( CIs) were extracted and pooled using fixed-effects models.


          Seven studies involving 1029 participants were included. The quality of these seven articles was all above five stars as assessed by NOS, and there was no significant publication bias in our meta-analysis. We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection ( OR: 2.00, 95% CI: 1.48–2.69).


          Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients. HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.



          2型糖尿病患者易出现幽门螺旋杆菌感染,并且有学者报道2型糖尿病患者出现蛋白尿和幽门螺旋杆菌感染有关,但此 观点仍然存在争议。


          本荟萃分析的目的主要是探求2型糖尿病肾病患者出现蛋白尿和幽门螺旋杆菌感染的关系,并为临床工作者及相关学 者提供建议。


          本荟萃分析纳入与2型糖尿病患者出现蛋白尿和HP感染有关的病例对照研究。在以下数据库搜索了2018年以前的英文 或中文研究:Pubmed,Cochrane图书馆,Medline,谷歌学术,中国知网(CNKI)和万方数据库,检索策略为:糖尿病蛋白 尿,糖尿病微量白蛋白尿,糖尿病白蛋白尿,糖尿病肾病,糖尿病肾功能不全,糖尿病并发症和糖尿病,分别结合幽门螺旋 杆菌。纳入文章的质量由2名实验人员分别使用NOS量表进行评估。 本研究采用固定效应模型分析整合相关数据。


          本荟萃分析纳入了7个病例对照研究共1029名参与者。7个病例对照研究的NOS评分均超过5颗星,且没有显著的发表偏 倚。分析结果显示,2型糖尿病患者合并幽门螺旋杆菌感染出现蛋白尿的风险是无幽门螺旋杆菌感染者的2倍(OR=2.00,95%CI (1.48,2.69))。


          本荟萃分析结果提示2型糖尿病患者出现蛋白尿和幽门螺旋杆菌的感染有关,幽门螺旋杆菌根治术可能是保护合并幽门 螺旋杆菌感染的糖尿病患者肾功能的有效方法。

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          Most cited references 38

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          Diabetic nephropathy (DN), a severe microvascular complication frequently associated with both type 1 and type 2 diabetes mellitus, is a leading cause of renal failure. The condition can also lead to accelerated cardiovascular disease and macrovascular complications. Currently available therapies have not been fully efficacious in the treatment of DN, suggesting that further understanding of the molecular mechanisms underlying the pathogenesis of DN is necessary for the improved management of this disease. Although key signal transduction and gene regulation mechanisms have been identified, especially those related to the effects of hyperglycaemia, transforming growth factor β1 and angiotensin II, progress in functional genomics, high-throughput sequencing technology, epigenetics and systems biology approaches have greatly expanded our knowledge and uncovered new molecular mechanisms and factors involved in DN. These mechanisms include DNA methylation, chromatin histone modifications, novel transcripts and functional noncoding RNAs, such as microRNAs and long noncoding RNAs. In this Review, we discuss the significance of these emerging mechanisms, how they mediate the actions of growth factors to augment the expression of extracellular matrix and inflammatory genes associated with DN and their potential usefulness as diagnostic biomarkers or novel therapeutic targets for DN.
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            Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China.
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              Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin.

              Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a protein that causes ulceration in the stomach of mice. However, the relationship between these two virulence factors is unknown. To define whether CagA and VacA are coexpressed in all clinical isolates and their relationships, we collected 43 clinical isolates of H. pylori and studied their genetic and phenotypic properties. Based on this analysis, most of the strains could be classified into two major types. Type I bacteria had the gene coding for CagA and expressed the CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the gene coding for CagA and did not express either the CagA protein or the vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%, respectively, of the 43 clinical isolates, while the remaining 28% had an intermediate phenotype, expressing CagA independently of VacA or vice versa. This finding shows that although it is present in most cytotoxic strains, CagA is not necessary for the expression of the vacuolating cytotoxin.

                Author and article information

                Chin Med J (Engl)
                Chin. Med. J
                Chinese Medical Journal
                Medknow Publications & Media Pvt Ltd (India )
                20 November 2018
                : 131
                : 22
                : 2734-2740
                [1 ]Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China
                [2 ]Department of Nephrology, Zhengzhou University; The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Key Laboratory of Accurate Diagnosis and Treatment of Chronic Kidney Diseases in Henan Province, Core Unit of National Kidney Disease Clinical Medical Research Center, Zhengzhou, Henan 450052, China
                Author notes
                Address for correspondence: Dr. Han-Yu Zhu, Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China E-Mail: kidney301@
                Copyright: © 2018 Chinese Medical Journal

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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