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Chua WK, Hong YK, Hu SW, Fan HC, Ting WH. A Significant Association between Type 1 Diabetes and Helicobacter pylori Infection: A Meta-Analysis Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:119. [PMID: 38256380 PMCID: PMC10821400 DOI: 10.3390/medicina60010119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/11/2023] [Accepted: 12/28/2023] [Indexed: 01/24/2024]
Abstract
Background and Objectives: Type 1 diabetes mellitus (T1DM) is a chronic and serious condition that is characterized by inadequate pancreatic-β-cells' insulin production. The connection between T1DM and Helicobacter pylori infection remains uncertain. This study aimed to conduct a systematic meta-analysis to examine the association between H. pylori infection, hemoglobin A1c levels, and the development of T1DM. Materials and Methods: The initial search identified 451 articles on the association between H. pylori infection and T1DM. Among them, 12 articles had 2797 participants who met the inclusion criteria for an advanced meta-analysis. Results: A significant association was observed between H. pylori infection and T1DM (OR 1.77, 95% CI 1.47-2.12, p < 0.0001), with heterogeneity: Tau2 = 0.47; Chi2 = 57.07, df = 11 (p < 0.0001); I2 = 81%. Subgroup analysis showed that H. pylori infection was significantly associated with a longer duration of T1DM and higher hemoglobin A1c levels (p < 0.001 for both) but not with age at T1DM diagnosis (p = 0.306). Conclusions: These findings contribute to the understanding of the association between H. pylori infection and T1DM and highlight the potential role of H. pylori in influencing the duration and glycemic control of diabetes. Therefore, pediatric patients who have longstanding T1DM and poor glycemic control should be screened for H. pylori infection.
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Affiliation(s)
- Wei-Kian Chua
- Division of Pediatric Endocrinology, Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 43503, Taiwan;
| | - Yi-Kai Hong
- Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan;
- International Center for Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan 70101, Taiwan
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Shu-Wei Hu
- Division of Pediatric Gastroenterology, Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
- Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan
| | - Hueng-Chuen Fan
- Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan
- Division of Pediatric Neurology, Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
- Department of Rehabilitation, Jenteh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan
| | - Wei-Hsin Ting
- Department of Pediatric Endocrinology, MacKay Children’s Hospital, Taipei 10449, Taiwan
- Department of Medicine, MacKay Medical College, New Taipei 25245, Taiwan
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Sevimligul G, Polat ZA, Gokce SF. Toxoplasma gondii and multiple sclerosis: a population-based case-control seroprevalence study, Central Anatolia, Turkey. Mult Scler Relat Disord 2023; 78:104871. [PMID: 37499340 DOI: 10.1016/j.msard.2023.104871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/23/2023] [Accepted: 07/04/2023] [Indexed: 07/29/2023]
Abstract
BACKGROUND Toxoplasma gondii, an obligate intracellular parasite, is prevalent in various mammalian species, as well as certain avian, reptilian, and cold-blooded organisms. While immunocompetent individuals generally remain asymptomatic, immunocompromised individuals may experience severe and life-threatening conditions. Multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system (CNS), is characterized by inflammation, demyelination, and axonal damage. Despite extensive research, the etiology and pathogenesis of MS remain incompletely understood. Given the strong affinity of T. gondii for the CNS, researchers have explored the potential association between T. gondii and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and MS. This study aimed to investigate the possible relationship between MS and T. gondii. METHODS A population-based incident cohort of MS patients in Sivas, Turkey, was used to randomly select MS patients. Age- and sex-matched controls were also randomly selected from the general population. A total of 182 MS patients and 182 controls were included in the study. Clinical and socio-demographic variables were recorded using a structured questionnaire. Blood samples were collected from MS patients, and Toxoplasma IgG and IgM antibodies were measured using the enzyme-linked immunosorbent assay technique. RESULTS Anti-Toxoplasma IgG antibodies were detected in 78 cases (42.9%) and 73 controls (40.1%) (p>0.05). Age, female sex, and consumption of raw meat were identified as risk factors for toxoplasmosis in both MS patients and controls. CONCLUSION In contrast to previous studies, this study did not find a significant difference in T. gondii seropositivity between the control group and MS patients. Further investigations are recommended to elucidate the precise relationship between MS patients and T. gondii.
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Affiliation(s)
- Gülgün Sevimligul
- Department of Parasitology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey..
| | - Zubeyda Akın Polat
- Department of Parasitology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
| | - Seyda Figul Gokce
- Department of Neurology, Cumhuriyet University School of Medicine, Sivas, Turkey
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Kahlam A, Khrais A, Khalessi A, Ahlawat S. Trends and Complication Rates in Ulcerative Colitis Patients With and Without Helicobacter pylori Infections. Cureus 2023; 15:e37345. [PMID: 37182047 PMCID: PMC10169286 DOI: 10.7759/cureus.37345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2023] [Indexed: 05/16/2023] Open
Abstract
Background Previous studies have shown an inverse relationship between ulcerative colitis (UC) and Helicobacter pylori infections (HPI). Though these two conditions have opposite geographic distributions, there may also be a physiological explanation for the decreased incidence of H. pylori infections in patients with UC. The purpose of this study is to analyze trends and complication rates of ulcerative colitis patients with and without HPI. Materials and methods The National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of UC, stratified by the presence of H. pylori infection. Patient demographics, length of stay, total hospital charges, and mortality were compared by H. pylori status. Additionally, complication rates were also compared between the two groups. Chi-squared and independent t-tests were used to compare outcomes and demographics, and multiple logistic regression was used to analyze primary and secondary outcomes. Results Patients with UC and HPI had a lower mortality rate (8.22 vs. 3.48, P<0.05, adjusted odds ratio [AOR] 0.33) and lower hospital charges ($65,652 vs. $47,557, p<0.05, AOR 1) with similar length of stay. Patients with UC and HPI also had lower rates of intestinal perforation (2.16% vs. 1.12%, p=0.05, AOR 0.408) and intrabdominal abscess formation (0.89% vs. 0.12%, AOR 0.165, p=0.072), though this difference was not significant. From 2001 to 2013, the incidence of UC has increased while the incidence of HPI has decreased. Conclusions The lower hospital charges and mortality rate as well as decreased rates of intestinal perforation and abscess formation suggest that there may be a physiologic role that HPI plays in modulating UC. Further studies into the interaction of these two conditions would be beneficial in clarifying their relationship and may help guide treatment of UC.
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Affiliation(s)
- Aaron Kahlam
- Internal Medicine, New Jersey Medical School, Newark, USA
| | - Ayham Khrais
- Internal Medicine, New Jersey Medical School, Newark, USA
| | - Ali Khalessi
- Gastroenterology and Hepatology, New Jersey Medical School, Newark, USA
| | - Sushil Ahlawat
- Gastroenterology and Hepatology, Downstate Health Sciences University, Brooklyn, USA
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Catchpole A, Zabriskie BN, Bassett P, Embley B, White D, Gale SD, Hedges D. Association between Toxoplasma gondii Infection and Type-1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:4436. [PMID: 36901457 PMCID: PMC10001633 DOI: 10.3390/ijerph20054436] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/21/2023] [Accepted: 02/25/2023] [Indexed: 06/18/2023]
Abstract
Type-1 diabetes, an autoimmune disease characterized by damage to pancreatic insulin-producing beta cells, is associated with adverse renal, retinal, cardiovascular, and cognitive outcomes, possibly including dementia. Moreover, the protozoal parasite Toxoplasma gondii has been associated with type-1 diabetes. To better characterize the association between type-1 diabetes and Toxoplasma gondii infection, we conducted a systematic review and meta-analysis of published studies that evaluated the relationship between type-1 diabetes and Toxoplasma gondii infection. A random-effects model based on nine primary studies (total number of participants = 2655) that met our inclusion criteria demonstrated a pooled odds ratio of 2.45 (95% confidence interval, 0.91-6.61). Removing one outlying study increased the pooled odds ratio to 3.38 (95% confidence interval, 2.09-5.48). These findings suggest that Toxoplasma gondii infection might be positively associated with type-1 diabetes, although more research is needed to better characterize this association. Additional research is required to determine whether changes in immune function due to type-1 diabetes increase the risk of infection with Toxoplasma gondii, infection with Toxoplasma gondii increases the risk of type-1 diabetes, or both processes occur.
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Affiliation(s)
- Ashley Catchpole
- The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
| | | | - Pierce Bassett
- The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
| | - Bradley Embley
- The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
| | - David White
- The Department of Micro and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
- The Department of Psychology, Brigham Young University, Provo, UT 84602, USA
| | - Shawn D. Gale
- The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
- The Department of Psychology, Brigham Young University, Provo, UT 84602, USA
| | - Dawson Hedges
- The Neuroscience Center, Brigham Young University, Provo, UT 84602, USA
- The Department of Psychology, Brigham Young University, Provo, UT 84602, USA
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Elwenspoek MM, Thom H, Sheppard AL, Keeney E, O'Donnell R, Jackson J, Roadevin C, Dawson S, Lane D, Stubbs J, Everitt H, Watson JC, Hay AD, Gillett P, Robins G, Jones HE, Mallett S, Whiting PF. Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling. Health Technol Assess 2022; 26:1-310. [PMID: 36321689 PMCID: PMC9638887 DOI: 10.3310/zuce8371] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma. OBJECTIVES The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care. DESIGN (1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives. DATA SOURCES For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used. REVIEW METHODS For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed. RESULTS People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents (n = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research. LIMITATIONS The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet. CONCLUSIONS Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia). FUTURE WORK Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed. STUDY REGISTRATION This study is registered as PROSPERO CRD42019115506 and CRD42020170766. FUNDING This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Martha Mc Elwenspoek
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Howard Thom
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Athena L Sheppard
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Edna Keeney
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Rachel O'Donnell
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Joni Jackson
- National Institute for Health and Care Research Applied Research Collaboration West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Cristina Roadevin
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Sarah Dawson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | | | | | - Hazel Everitt
- Primary Care Research Centre, Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Jessica C Watson
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Alastair D Hay
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Peter Gillett
- Paediatric Gastroenterology, Hepatology and Nutrition Department, Royal Hospital for Sick Children, Edinburgh, UK
| | - Gerry Robins
- Department of Gastroenterology, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Hayley E Jones
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Sue Mallett
- Centre for Medical Imaging, University College London, London, UK
| | - Penny F Whiting
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Toxoplasma gondii and multiple sclerosis: a population-based case-control study. Sci Rep 2020; 10:18855. [PMID: 33139781 PMCID: PMC7606604 DOI: 10.1038/s41598-020-75830-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 10/09/2020] [Indexed: 01/02/2023] Open
Abstract
According to the hygiene hypothesis, parasites could have a protective role in the development of Multiple Sclerosis (MS). Our aim was to assess the association between presence of anti-Toxoplasma gondii antibodies and MS. MS patients were randomly selected from a population-based incident cohort of MS patients in the city of Catania. Age and sex-matched controls were randomly selected from the general population. Clinical and sociodemographic variables were recorded with a structured questionnaire and a blood sample was taken for serological analysis. Specific T. gondii IgG have been detected with a commercial kit. Adjusted Odds Ratios (ORs) were estimated using unconditional logistic regression. 129 MS subjects (66.7% women with a mean age 44.7 ± 11.0 years) and 287 controls (67.3% women with a mean age 48.1 ± 15.6 years) have been enrolled in the study. Anti-T. gondii antibodies were found in 38 cases (29.5%) and 130 controls (45.4%) giving an adjusted OR of 0.56 (95%CI 0.34–0.93). History of mononucleosis and high educational level were significantly associated with MS (adjOR 2.22 and 1.70 respectively) while an inverse association was found between high educational level and T. gondii seropositivity (adjOR 0.42). Our results further support the protective role of parasitic infections in MS.
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Mansori K, Moradi Y, Naderpour S, Rashti R, Moghaddam AB, Saed L, Mohammadi H. Helicobacter pylori infection as a risk factor for diabetes: a meta-analysis of case-control studies. BMC Gastroenterol 2020; 20:77. [PMID: 32209055 PMCID: PMC7092473 DOI: 10.1186/s12876-020-01223-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There are several studies with varied and mixed results about the possible relationship between H. pylori and diabetes. Therefore, this current meta-analysis performed to determine the association between H. pylori infection and the risk of diabetes mellitus. METHODS A systematic literature searches of international databases, including Medline (PubMed), Web of Sciences, Scopus, EMBASE, and CINHAL (January 1990-March 2019) was conducted to identify studies investigating the relationship between H. pylori infection and diabetes mellitus. Only case-control studies were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Stratified and subgroup analyses were performed to explore heterogeneity between studies and assess effects of study quality. Logarithm and standard error logarithm odds ratio (OR) were also used for meta-analysis. RESULTS A total of 41 studies involving 9559 individuals (case; 4327 and control; 5232) were analyzed. The pooled estimate of the association between H. pylori infection with diabetes was OR = 1.27 (95% CI 1.11 to 1.45, P = 0.0001, I2 = 86.6%). The effect of H. pylori infection on diabetes mellitus (both types), type 1 and type 2 diabetes was 1.17 (95% CI 0.94 to 1.45), 1.19 (95% CI 0.98 to 1.45), and 1.43 (95% CI 1.11 to 1.85) respectively. Subgroup analysis by the geographical regions showed in Asian population risk of the effect of H. pylori infection on diabetes was slightly higher than other population, CONCLUSION: In overall a positive association between H. pylori infection and diabetes mellitus was found.
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Affiliation(s)
- Kamyar Mansori
- Department of Biostatistics and Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Yousef Moradi
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Sara Naderpour
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Roya Rashti
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ali Baradaran Moghaddam
- Research Center of Pediatric Infection Diseases, Institute of Immunology and Infection Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Lotfolah Saed
- Department of Endocrinology, Faculty of Medicine, Kurdistan University of Medical Science, Sanandaj, Iran
| | - Hedyeh Mohammadi
- Faculty of Medicine, Kurdistan University of Medical Science, Sanandaj, Iran
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Khattab HM, El Bassiouni SO, Abuelela MH, Abd Elsalam DO. Seroprevalence of Toxoplasma gondii among a group of Egyptian patients with type I diabetes mellitus. BULLETIN OF THE NATIONAL RESEARCH CENTRE 2019; 43:20. [DOI: 10.1186/s42269-019-0059-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 01/21/2019] [Indexed: 09/01/2023]
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Rahman YA, Ahmed LAW, Hafez RMM, Ahmed RMM. Helicobacter pylori and its hematological effect. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_103_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Abstract
PURPOSE OF REVIEW Infections play a role in the pathogenesis of autoimmune diseases (AID). Several bacterial and viral pathogens play a double role, as both inducers and inhibitors of AID. In this review, we will present current evidence and discuss different aspects of this notion. RECENT FINDINGS Infectors that both inhibit and induce AID include Helicobacter pylori, Klebsiella pneumoniae, hepatitis B virus, group B Coxsackieviruses, Epstein-Barr virus and Lymphocytic choriomeningitis virus. Numerous AID are affected by infections, including polyarteritis nodosa, inflammatory bowel disease, and type 1 diabetes. Some pathogens, such as group B Coxsackieviruses, may induce and inhibit the development of the same AID. This reveals a complex role of infections in autoimmunity pathogenesis. SUMMARY Elucidating the exact role of each pathogen on each specific AID is important, as this will enable evaluating the manipulation of these infections in the treatment of AID.
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Adeno-associated virus neutralising antibodies in type 1 diabetes mellitus. Gene Ther 2019; 26:250-263. [PMID: 30962537 DOI: 10.1038/s41434-019-0076-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 03/07/2019] [Accepted: 03/13/2019] [Indexed: 12/26/2022]
Abstract
Recombinant Adeno-associated viruses (AAVs) are an attractive vector for gene therapy delivery which may be blocked by AAV neutralising antibodies (NAbs). As Type 1 Diabetes (T1DM) is an endocrine disease of immunological origin, it is likely that NAb profiles are altered in the disease. In this study NAb to AAV2, AAV5, AAV6, and AAV8 in 72 subjects with T1DM and 45 non-diabetic patients were measured over a 4-year follow-up period. AAV2 NAb titres were significantly lower in non-diabetic subjects (P = 0.036). The T1DM group had more AAV8 NAb activity at baseline (P = 0.019), whilst after 4 years follow-up the T1DM group displayed developed increased AAV 5 (P = 0.03), 6 (P = 0.03) and 8 (P = 0.002) activity relative to the control group, however, overall AAV5 and 8 NAb levels were very low in patients <40. AAV NAb titre activity and prevalence generally appears higher in T1DM, however, low levels of AAV 5 and 8, particular in younger adult age groups at which T1DM can be targeted, could make these attractive vectors to target the disease.
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Toxoplasma gondii Infection in Diabetes Mellitus Patients in China: Seroprevalence, Risk Factors, and Case-Control Studies. BIOMED RESEARCH INTERNATIONAL 2018; 2018:4723739. [PMID: 30662909 PMCID: PMC6312584 DOI: 10.1155/2018/4723739] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 08/05/2018] [Accepted: 11/06/2018] [Indexed: 12/12/2022]
Abstract
The association between Toxoplasma gondii (T. gondii) infection and diabetes mellitus remains controversial. With the improvement of living standards, the prevalence rate of diabetes is steadily increasing in China. Thus, it is necessary to explore the possible association between toxoplasmosis and diabetes mellitus in China. Hence, case-control studies were conducted to explore the T. gondii seroprevalence and identify the risk factors and possible transmission routes of T. gondii infection in different types of diabetes, including type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM) patients in China. Four hundred serum samples for each type of diabetes mellitus, matched with 400 control subjects for each group, were collected and examined for anti-T. gondii IgG and IgM antibodies using commercially available enzyme immunoassay kits. The total T. gondii seroprevalence in T1DM, T2DM, and GDM patients was 16.50%, 23.50%, and 21.25%, respectively. Each type of diabetes mellitus patients had a significantly higher T. gondii seroprevalence than the control subjects. Multivariate regression identified three variables as risk factors for T. gondii infection in diabetes patients, including keeping cats at home and consumption of raw oysters for T1DM patients and consumption of raw/undercooked meat and raw oysters for T2DM patients, which may help to guide future research and control policies in diabetes mellitus patients.
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Saberi R, Sharif M, Sarvi S, Aghayan SA, Hosseini SA, Anvari D, Nayeri Chegeni T, Hosseininejad Z, Daryani A. Is Toxoplasma gondii playing a positive role in multiple sclerosis risk? A systematic review and meta-analysis. J Neuroimmunol 2018; 322:57-62. [DOI: 10.1016/j.jneuroim.2018.06.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Revised: 06/01/2018] [Accepted: 06/13/2018] [Indexed: 12/19/2022]
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Kozhakhmetova A, Wyatt RC, Caygill C, Williams C, Long AE, Chandler K, Aitken RJ, Wenzlau JM, Davidson HW, Gillespie KM, Williams AJK. A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study. Clin Exp Immunol 2018; 192:251-258. [PMID: 29431870 DOI: 10.1111/cei.13115] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2018] [Indexed: 12/28/2022] Open
Abstract
Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.
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Affiliation(s)
- A Kozhakhmetova
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - R C Wyatt
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - C Caygill
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - C Williams
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - A E Long
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - K Chandler
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - R J Aitken
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - J M Wenzlau
- The Barbara Davis Center for Diabetes, University of Colorado, Denver, CO, USA
| | - H W Davidson
- The Barbara Davis Center for Diabetes, University of Colorado, Denver, CO, USA
| | - K M Gillespie
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - A J K Williams
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
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Wang S, Chen Y, Xu X, Hu W, Shen H, Chen J. Prevalence of hepatitis B virus and hepatitis C virus infection in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Oncotarget 2017; 8:102437-102445. [PMID: 29254259 PMCID: PMC5731969 DOI: 10.18632/oncotarget.22261] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 09/22/2017] [Indexed: 02/06/2023] Open
Abstract
We attempted to explore the prevalence of HBV and HCV infections in patients with systemic lupus erythematous (SLE) via a systematic review. Articles published before June 2017 and, related to prevalence rates for HBV and HCV infection in SLE patient were identified in PubMed, Embase, CNKI, and Wanfang databases. Based on these searches 22 studies were selected for further analysis. The OR of HBsAg positive rate in SLE patients compared with control population was 0.28, with significant heterogeneity identified among the studies (I2 = 92%, P < 0.00001). Following exclusion of one study, the adjusted OR of HBsAg in patients with SLE was 0.24, and no significant heterogeneity was observed (I2 = 32%, P = 0.15). The adjusted OR of HBcAb positive rate in SLE patients compared with control population was 0.40, with no significant heterogeneity between studies (I2 = 0%, P = 0.56). The risk of having HCV infection by SLE patients was higher compared with the control subjects (OR = 2.91). In conclusion, this meta-analysis suggested that SLE might exert a role of protection against HBV but not for HCV infection. Further epidemiological and experimental studies are necessary to explore the role and mechanisms by which SLE affects HBV/HCV infections.
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Affiliation(s)
- Sen Wang
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Yuxin Chen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xuejing Xu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Wei Hu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Han Shen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Junhao Chen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
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Helicobacter pylori Infection Is Associated with Type 2 Diabetes, Not Type 1 Diabetes: An Updated Meta-Analysis. Gastroenterol Res Pract 2017; 2017:5715403. [PMID: 28883831 PMCID: PMC5572635 DOI: 10.1155/2017/5715403] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 05/14/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Extragastric manifestations of Helicobacter pylori (H. pylori) infection have been reported in many diseases. However, there are still controversies about whether H. pylori infection is associated with diabetes mellitus (DM). This study was aimed at answering the question. METHODS A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reporting H. pylori infection in both DM and non-DM individuals were recruited. RESULTS 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence of H. pylori infection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69, P < 0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77-1.96, P = 0.38). CONCLUSION Our meta-analysis suggested that there is significantly higher prevalence of H. pylori infection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.
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Koskderelioglu A, Afsar I, Pektas B, Gedizlioglu M. Is Toxoplasma gondii infection protective against multiple sclerosis risk? Mult Scler Relat Disord 2017. [DOI: 10.1016/j.msard.2017.04.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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18
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Alvarado-Esquivel C, Loera-Moncivais N, Hernandez-Tinoco J, Sanchez-Anguiano LF, Hernandez-Madrid G, Rabago-Sanchez E, Centeno-Tinoco MM, Sandoval-Carrillo AA, Salas-Pacheco JM, Campos-Moreno OV, Antuna-Salcido EI. Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A Matched Case-Control Study in a Mexican Population. J Clin Med Res 2017; 9:508-511. [PMID: 28496551 PMCID: PMC5412524 DOI: 10.14740/jocmr3029w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2017] [Indexed: 12/20/2022] Open
Abstract
Background Very little is known about the association between infection with Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and gender-matched case-control study to determine the association of T. gondii infection and diabetes mellitus. Methods Cases included 156 patients with diabetes mellitus and 156 controls without diabetes mellitus who attended in two public clinics in Durango City, Mexico. Sera of cases and controls were tested for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially available enzyme-linked fluorescence assays (ELFA). Results Anti-T. gondii IgG antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156 controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P = 0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10 cases and five controls with seropositivity to anti-T. gondii IgG antibodies were positive for anti-T. gondii IgM antibodies. Stratification by gender showed similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 - 31.19; P = 0.61). Conclusions We conclude that there is not serological evidence of an association between T. gondii infection and diabetes mellitus in the studied subjects in Durango City, Mexico. Further studies to elucidate the role of T. gondii in diabetes should be conducted.
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Affiliation(s)
- Cosme Alvarado-Esquivel
- Faculty of Medicine and Nutrition, Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Dgo, Mexico
| | - Nayely Loera-Moncivais
- Faculty of Medicine and Nutrition, Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Dgo, Mexico
| | - Jesus Hernandez-Tinoco
- Institute for Scientific Research "Dr. Roberto Rivera Damm", Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Durango, Mexico
| | - Luis Francisco Sanchez-Anguiano
- Institute for Scientific Research "Dr. Roberto Rivera Damm", Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Durango, Mexico
| | | | - Elizabeth Rabago-Sanchez
- Faculty of Medicine and Nutrition, Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Dgo, Mexico.,Hospital General de Durango, Secretaria de Salud, Avenida 5 de febrero y Norman Fuentes, 34000 Durango, Dgo, Mexico
| | | | - Ada A Sandoval-Carrillo
- Institute for Scientific Research "Dr. Roberto Rivera Damm", Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Durango, Mexico
| | - Jose M Salas-Pacheco
- Institute for Scientific Research "Dr. Roberto Rivera Damm", Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Durango, Mexico
| | | | - Elizabeth Irasema Antuna-Salcido
- Institute for Scientific Research "Dr. Roberto Rivera Damm", Juarez University of Durango State, Avenida Universidad S/N, 34000 Durango, Durango, Mexico
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Majidiani H, Dalvand S, Daryani A, Galvan-Ramirez MDLL, Foroutan-Rad M. Is chronic toxoplasmosis a risk factor for diabetes mellitus? A systematic review and meta-analysis of case–control studies. Braz J Infect Dis 2016; 20:605-609. [PMID: 27768900 PMCID: PMC9427549 DOI: 10.1016/j.bjid.2016.09.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Revised: 08/28/2016] [Accepted: 09/02/2016] [Indexed: 12/21/2022] Open
Abstract
Introduction The global protozoan parasite, Toxoplasma gondii, infects many warm-blooded animals and humans by employing different transmission routes. There have been some recent studies on the probable relevance of infectious agents and diabetes. Therefore, we conducted a systematic review and meta-analysis to identify the possible association between chronic toxoplasmosis and diabetes mellitus. Methods This study was conducted following the general methodology recommended for systematic reviews and meta-analysis. Nine English literature databases (Google scholar, PubMed, Scopus, Web of science, Science Direct, Ovid, ProQuest, IngentaConnect, and Wiley Online Library) were searched, up to January 2016. Random effects model was used to determine odds ratios and their 95% confidence intervals. Results Our review resulted in a total of seven publications meeting the inclusion criteria. Because of significant heterogeneity, we estimated a common OR by a random effects model at 1.10 (95% CI = 0.13–9.57) with p = 0.929 and 2.39 (95% CI = 1.20–4.75) with p = 0.013 for type 1 and type 2 diabetes mellitus, respectively. Conclusion Despite the limitations such as low number of studies, this meta-analysis suggests chronic toxoplasmosis as a possible risk factor for type 2 DM. However, based on random effects model no statistically significant association was observed between T. gondii and type 1 DM. It is highly recommended for researchers to carry out more accurate studies aiming to better understand this association.
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Herpesvirus Infections and Transglutaminase Type 2 Antibody Positivity in Childhood: The Generation R Study. J Pediatr Gastroenterol Nutr 2016; 63:423-30. [PMID: 26881413 DOI: 10.1097/mpg.0000000000001163] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES Persistent viral infections have been implicated in the etiology of autoimmune diseases in adulthood, but it is not known whether herpesviruses are associated with the development of celiac disease autoimmunity in childhood. We assessed whether herpesvirus infections are associated with transglutaminase type 2 antibody (TG2A) concentrations in children at 6 years of age. METHODS The present study was embedded within a population-based prospective cohort study. Serum immunoglobulin G levels against Epstein-Barr virus, cytomegalovirus (CMV), and herpes simplex virus type 1 were measured by enzyme-linked immunosorbent assay , and TG2A concentrations with fluorescence enzyme immunoassay in 4420 children at 6 years of age. Children were categorized based on TG2A concentrations into negative (<7 U/mL), positive (≥7-70 U/mL), and strongly positive (≥70 U/mL), that is, 10 times upper limit normal. RESULTS Fifty-nine children (1.3%) were TG2A positive, and of these 31 (53%) had concentrations 70 U/mL or more. Children with TG2A concentrations 70 U/mL or more were less often infected with CMV (adjusted odds ratio (aOR) 0.38, 95% CI 0.14-0.98, P = 0.04) and with any of the 3 viruses (aOR 0.38, 95% CI 0.18-0.78, P < 0.01) than children with TG2A negative concentrations. In addition, children with TG2A concentrations 70 U/mL or more were less often infected with 2 or more viruses than children with TG2A negative concentrations (aOR 0.15, 95% CI 0.03-0.65, P = 0.01). CONCLUSIONS Both CMV single infection and combined CMV, Epstein-Barr virus and/or herpes simplex virus type 1 infections are inversely associated with strongly TG2A positivity. This may indicate a protective effect of herpesvirus infections in the pathogenesis of celiac disease autoimmunity.
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Bonfigli AR, Boemi M, Festa R, Bonazzi P, Brandoni G, Spazzafumo L, Olivieri F, Ceriello A, Genovese S, Testa R. Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 2016; 26:893-898. [PMID: 27480449 DOI: 10.1016/j.numecd.2016.06.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 06/16/2016] [Accepted: 06/24/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER ACTRN12609000255280 (https://www.anzctr.org.au/).
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Affiliation(s)
- A R Bonfigli
- Scientific Direction, Italian National Research Center on Aging (INRCA), Ancona, Italy.
| | - M Boemi
- Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy
| | - R Festa
- Department of Primary Care, ASUR Marche, Italy
| | - P Bonazzi
- Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy
| | - G Brandoni
- Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy
| | - L Spazzafumo
- Statistic and Biometry Centre, Italian National Research Center on Aging (INRCA), Ancona, Italy
| | - F Olivieri
- Centre of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA), Ancona, Italy; Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
| | - A Ceriello
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
| | - S Genovese
- Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni, Italy
| | - R Testa
- Experimental Models in Clinical Pathology, Italian National Research Center on Aging (INRCA), Ancona, Italy
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Do differences in Toxoplasma prevalence influence global variation in secondary sex ratio? Preliminary ecological regression study. Parasitology 2016; 143:1193-203. [DOI: 10.1017/s0031182016000597] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
SUMMARYSex of the fetus is genetically determined such that an equal number of sons and daughters are born in large populations. However, the ratio of female to male births across human populations varies significantly. Many factors have been implicated in this. The theory that natural selection should favour female offspring under suboptimal environmental conditions implies that pathogens may affect secondary sex ratio (ratio of male to female births). Using regression models containing 13 potential confounding factors, we have found that variation of the secondary sex ratio can be predicted by seroprevalence of Toxoplasma across 94 populations distributed across African, American, Asian and European continents. Toxoplasma seroprevalence was the third strongest predictor of secondary sex ratio, β = −0·097, P < 0·01, after son preference, β = 0·261, P < 0·05, and fertility, β = −0·145, P < 0·001. Our preliminary results suggest that Toxoplasma gondii infection could be one of the most important environmental factors influencing the global variation of offspring sex ratio in humans. The effect of latent toxoplasmosis on public health could be much more serious than it is usually supposed to be.
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Kankova S, Flegr J, Calda P. An elevated blood glucose level and increased incidence of gestational diabetes mellitus in pregnant women with latent toxoplasmosis. Folia Parasitol (Praha) 2015; 62. [DOI: 10.14411/fp.2015.056] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 08/03/2015] [Indexed: 01/16/2023]
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Stascheit F, Paul F, Harms L, Rosche B. Toxoplasma gondii seropositivity is negatively associated with multiple sclerosis. J Neuroimmunol 2015. [DOI: 10.1016/j.jneuroim.2015.05.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Parra-Medina R, Molano-Gonzalez N, Rojas-Villarraga A, Agmon-Levin N, Arango MT, Shoenfeld Y, Anaya JM. Prevalence of celiac disease in latin america: a systematic review and meta-regression. PLoS One 2015; 10:e0124040. [PMID: 25942408 PMCID: PMC4420463 DOI: 10.1371/journal.pone.0124040] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Accepted: 03/10/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in susceptible individuals, and its prevalence varies depending on the studied population. Given that information on CD in Latin America is scarce, we aimed to investigate the prevalence of CD in this region of the world through a systematic review and meta-analysis. METHODS AND FINDINGS This was a two-phase study. First, a cross-sectional analysis from 981 individuals of the Colombian population was made. Second, a systematic review and meta-regression analysis were performed following the Preferred Reporting Items for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review, 72 studies were considered. The estimated prevalence of CD in Latin Americans ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies and/or biopsies). CONCLUSIONS Although CD seems to be a rare condition in Colombians; the general prevalence of the disease in Latin Americans seemingly corresponds to a similar scenario observed in Europeans.
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Affiliation(s)
- Rafael Parra-Medina
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogotá, Colombia
| | - Nicolás Molano-Gonzalez
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogotá, Colombia
| | - Adriana Rojas-Villarraga
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogotá, Colombia
| | - Nancy Agmon-Levin
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Sackler Medical School, Tel Aviv University, Tel Aviv, Israel
| | - Maria-Teresa Arango
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogotá, Colombia
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Doctoral Program in Biomedical Sciences Universidad del Rosario, Bogotá, Colombia
| | - Yehuda Shoenfeld
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
- Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Juan-Manuel Anaya
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 #63-C-69, Bogotá, Colombia
- * E-mail:
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Sanz Y, Olivares M, Moya-Pérez Á, Agostoni C. Understanding the role of gut microbiome in metabolic disease risk. Pediatr Res 2015; 77:236-44. [PMID: 25314581 DOI: 10.1038/pr.2014.170] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/02/2014] [Indexed: 02/06/2023]
Abstract
The gut microbiota structure, dynamics, and function result from interactions with environmental and host factors, which jointly influence the communication between the gut and peripheral tissues, thereby contributing to health programming and disease risk. Incidence of both type-1 and type-2 diabetes has increased during the past decades, suggesting that there have been changes in the interactions between predisposing genetic and environmental factors. Animal studies show that gut microbiota and its genome (microbiome) influence alterations in energy balance (increased energy harvest) and immunity (inflammation and autoimmunity), leading to metabolic dysfunction (e.g., insulin resistance and deficiency). Thus, although they have different origins, both disorders are linked by the association of the gut microbiota with the immune-metabolic axis. Human studies have also revealed shifts in microbiome signatures in diseased subjects as compared with controls, and a few of them precede the development of these disorders. These studies contribute to pinpointing specific microbiome components and functions (e.g., butyrate-producing bacteria) that can protect against both disorders. These could exert protective roles by strengthening gut barrier function and regulating inflammation, as alterations in these are a pathophysiological feature of both disorders, constituting common targets for future preventive approaches.
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Affiliation(s)
- Yolanda Sanz
- Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain
| | - Marta Olivares
- Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain
| | - Ángela Moya-Pérez
- Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain
| | - Carlo Agostoni
- Pediatric Clinic, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
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Papamichael K, Konstantopoulos P, Mantzaris GJ. Helicobacter pylori infection and inflammatory bowel disease: Is there a link? World J Gastroenterol 2014; 20:6374-6385. [PMID: 24914359 PMCID: PMC4047323 DOI: 10.3748/wjg.v20.i21.6374] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 01/07/2014] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is one of the most widely spread infectious diseases in humans. It can cause chronic gastritis, peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders. H. pylori elicit a chronic systemic inflammatory response which, under certain conditions, may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases. Although the pathogenesis of inflammatory bowel disease (IBD) is unknown, it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible. Several bacterial and viral agents have been implicated in the aetiology of IBD. In theory, H. pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways. Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations. However, the epidemiological data fail to support this association. In fact, various studies indicate that the prevalence of H. pylori infection is low in patients with IBD, suggesting a protective role for this infection in the development of IBD. In this report, we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H. pylori infection and IBD.
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Flegr J, Prandota J, Sovičková M, Israili ZH. Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS One 2014; 9:e90203. [PMID: 24662942 PMCID: PMC3963851 DOI: 10.1371/journal.pone.0090203] [Citation(s) in RCA: 415] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Accepted: 01/22/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. AIMS OF THE STUDY The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. METHODS AND FINDINGS Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. CONCLUSIONS The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.
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Affiliation(s)
- Jaroslav Flegr
- Department of Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic
| | - Joseph Prandota
- Department of Social Pediatrics, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland
| | - Michaela Sovičková
- Department of Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic
| | - Zafar H. Israili
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
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Wang F, Liu J, Lv Z. Association of Helicobacter pylori infection with diabetes mellitus and diabetic nephropathy: a meta-analysis of 39 studies involving more than 20,000 participants. ACTA ACUST UNITED AC 2013; 45:930-8. [PMID: 24143873 DOI: 10.3109/00365548.2013.844351] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Helicobacter pylori infects more than half of the world's population. The aim of this study was to quantify the association between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy, and to detect at which stage the infection might have higher pathogenicity in the disease-free status-diabetes mellitus-diabetic nephropathy process. METHODS A literature search was performed to identify studies published between 1997 and 2012 for relative risk estimates. Fixed and random effects meta-analytical techniques were conducted for diabetes mellitus and diabetic nephropathy. RESULTS Thirty-seven case-control studies and 2 cohort studies were included. H. pylori was associated with an increased risk of each type of diabetes mellitus (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.82-2.20, p for heterogeneity = 0.07). The infection was also associated with increased risks of type 1 and type 2 diabetes mellitus, separately (OR 1.99, 95% CI 1.52-2.60, p for heterogeneity = 0.15, and OR 2.15, 95% CI 1.81-2.55, p for heterogeneity = 0.24, respectively). In addition, we found a significant association between H. pylori infection and diabetic nephropathy risk (OR 1.60, 95% CI 1.10-2.33, p for heterogeneity = 0.44). CONCLUSIONS Our meta-analyses suggest a relationship between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy. The bacterium may be able to play its pathogenic role in the whole disease process, and this action may be stronger in type 2 diabetic patients than in type 1 diabetic patients.
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Affiliation(s)
- Feng Wang
- From the Department of Internal Medicine, Tianjin Union Medicine Center and Tianjin People's Hospital
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Haeseker MB, Pijpers E, Dukers-Muijrers NH, Nelemans P, Hoebe CJ, Bruggeman CA, Verbon A, Goossens VJ. Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study. IMMUNITY & AGEING 2013; 10:30. [PMID: 23880245 PMCID: PMC3726516 DOI: 10.1186/1742-4933-10-30] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Accepted: 07/21/2013] [Indexed: 11/10/2022]
Abstract
Background Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored. Results Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD. Conclusions Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.
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Affiliation(s)
- Michiel B Haeseker
- Department of Medical Microbiology, Maastricht University Medical Centre, P, Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands.
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Craig ME, Nair S, Stein H, Rawlinson WD. Viruses and type 1 diabetes: a new look at an old story. Pediatr Diabetes 2013; 14:149-58. [PMID: 23517503 DOI: 10.1111/pedi.12033] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Revised: 02/15/2013] [Accepted: 02/18/2013] [Indexed: 12/21/2022] Open
Abstract
Epidemiological data suggesting an infectious origin of diabetes pre-date the discovery of insulin; indeed it was the variation in mortality rates from diabetes that led Gunderson to hypothesise that a virus with 'selective affinity for the pancreas' may cause 'acute diabetes' in youth (1). He noted an increase in deaths from diabetes in young people aged 10-20 yr in Norway from 1900 to 1921 following epidemics of parotitis, with a lag time of 3-4 yr between infection and death. In Norway, Denmark,France, and America, the increase in deaths from diabetes exceeded the expected number based on population growth; lending further weight to the proposal that diabetes was caused by infection. Since that time,a large body of epidemiological, clinical and experimental research, in humans, cellular and animal models, has provided further insights into the contribution of infections in the development of type 1 diabetes.Epidemiological evidence for a viral aetiology of diabetes A substantial body of epidemiological data point to a significant contribution of the environment in the development of type 1 diabetes,although much of the evidence is not specific to viruses per se. These data include rising rates of type 1 diabetes in both developed and developing countries in recent decades (2, 3) and a reduced contribution of high risk human leucocyte antigen (HLA) genotypes (4, 5), indicating that non-genetic factors are important. Similarly, the pairwise concordance between monozygotic twins for type 1 diabetes of less than 40%, and the observation that the incidence of diabetes in migrant children reflects that of their adopted country (6, 7), provide circumstantial evidence that environmental agents contribute to the disease. Space-time clustering in the presentation of type 1 diabetes (8-10) and clustering of births in children who subsequently develop diabetes (11) support a direct role for infections in the initiation and acceleration of the disease process.
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Affiliation(s)
- Maria E Craig
- School of Women's and Children's Health, University of New South Wales, Kensington, NSW, 2052, Australia.
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Zhou X, Zhang C, Wu J, Zhang G. Association between Helicobacter pylori infection and diabetes mellitus: a meta-analysis of observational studies. Diabetes Res Clin Pract 2013; 99:200-8. [PMID: 23395214 DOI: 10.1016/j.diabres.2012.11.012] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Revised: 10/27/2012] [Accepted: 11/15/2012] [Indexed: 02/07/2023]
Abstract
AIMS Some studies have shown Helicobacter pylori (H. pylori) infection to be associated with diabetes mellitus, but the relationship remains controversial. This meta-analysis was designed to quantify the association between H. pylori infection and diabetes. METHODS A computerized search of PubMed and Embase was carried out. Studies that provided data on H. pylori infection in both diabetes and control groups were selected. An unconditional logistic regression model was used to analyze potential parameters related to H. pylori prevalence. Subgroup analyses were conducted for types of diabetes, methods of detection, geographical distribution, hemoglobin A1c (HbA1c) levels and evidence grade. RESULT Forty-one studies were identified, involving 14,080 patients, with a total H. pylori infection rate of 42.29%. The OR for H. pylori infection was increased to 1.33 (95% CI: 1.08-1.64; P=0.008) among the patients with diabetes. Subgroup analysis revealed a significantly higher infection rate of H. pylori in the type 2 diabetes group versus the control group: OR=1.76, 95% CI: 1.40-2.21, P<0.00001. CONCLUSIONS The pooled data suggests a trend toward more frequent H. pylori infections in diabetes patients, especially in type 2 diabetes patients. As this is a meta-analysis of observational studies, more randomized controlled trials should be done in the future.
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Affiliation(s)
- Xiaoying Zhou
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
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Ram M, Barzilai O, Shapira Y, Anaya JM, Tincani A, Stojanovich L, Bombardieri S, Bizzaro N, Kivity S, Agmon Levin N, Shoenfeld Y. Helicobacter pylori serology in autoimmune diseases – fact or fiction? Clin Chem Lab Med 2013; 51:1075-82. [DOI: 10.1515/cclm-2012-0477] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Accepted: 09/19/2012] [Indexed: 02/06/2023]
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Sener AG, Afsar I. Infection and autoimmune disease. Rheumatol Int 2012; 32:3331-8. [PMID: 22811010 DOI: 10.1007/s00296-012-2451-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Accepted: 07/07/2012] [Indexed: 10/28/2022]
Abstract
Most infectious agents, such as viruses, bacteria and parasites, can trigger autoimmunity via different mechanisms. The development of an autoimmune disorder after infection tends to occur in genetically susceptible individuals. Some parameters, such as genetic predisposition, feature of the infectious agent and sometimes protective effect of the infections, have a significant role in this process. These parameters and various pathogens that could lead to enhancement or exacerbation of autoimmune disease were examined in this review. Recent studies were reviewed from a microbiological perspective.
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Affiliation(s)
- Asli Gamze Sener
- Microbiology and Clinical Microbiology Department, Ataturk Training and Research Hospital, Izmir, Turkey.
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35
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Mercalli A, Lampasona V, Klingel K, Albarello L, Lombardoni C, Ekström J, Sordi V, Bolla A, Mariani A, Bzhalava D, Dillner J, Roivainen M, Bosi E, Piemonti L. No evidence of enteroviruses in the intestine of patients with type 1 diabetes. Diabetologia 2012; 55:2479-88. [PMID: 22684312 DOI: 10.1007/s00125-012-2591-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 04/24/2012] [Indexed: 12/15/2022]
Abstract
AIMS/HYPOTHESIS The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes. METHODS Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 control individuals and 27 individuals with coeliac disease were analysed for the presence of enterovirus RNA by using both radioactive in-situ hybridisation and real-time RT-PCR and for the presence of enterovirus proteins by immunostaining with antibodies against VP1 and VP4-2-3 capsid proteins and virus polymerase. Lymphocytic enteropathy and serum anti-VP1 antibodies were also evaluated at the time of biopsy. Moreover, high-throughput sequencing was performed to identify viral transcripts or genomes. RESULTS Enterovirus was not detected by in-situ hybridisation or RT-PCR in any of the individuals tested. Immunohistology revealed a few stained cells in the intestinal epithelium in a low number of individuals, with no difference between diabetic and non-diabetic individuals. Levels of serum IgG against VP1 did not differ between control individuals and those with diabetes or coeliac disease and no evidence of diabetes-related lymphocytic enteropathy was detected. High-throughput sequencing did not reveal specific enterovirus sequences in the gut mucosa of individuals with type 1 diabetes. CONCLUSIONS/INTERPRETATION Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.
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Affiliation(s)
- A Mercalli
- Diabetes Research Institute, HSR-DRI, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy
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Shapira Y, Poratkatz BS, Gilburd B, Barzilai O, Ram M, Blank M, Lindeberg S, Frostegård J, Anaya JM, Bizzaro N, Jara LJ, Damoiseaux J, Shoenfeld Y, Levin NA. Geographical differences in autoantibodies and anti-infectious agents antibodies among healthy adults. Clin Rev Allergy Immunol 2012; 42:154-63. [PMID: 21229335 DOI: 10.1007/s12016-010-8241-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Much is known about the geoepidemiology of defined autoimmune diseases (AD); however, there is currently limited data regarding the prevalence of autoantibodies among healthy populations of different geographical areas. The aim of this study was to evaluate a large profile of autoantibodies in healthy adults from distinct global regions as well as the prevalence of anti-infectious agents antibodies in those regions. Sera samples from 557 healthy donors were obtained at six centers located in different countries (i.e., Italy, Netherlands, Israel, Mexico, Columbia, Papua New Guinea (Kitavans)). Sera were tested for the presence of antinuclear antibodies (ANA) and autoantibodies associated with thrombophilia, vasculitis, and gastrointestinal (GI) disease. Sera samples were also screened for antibodies against infectious agents (i.e., EBV, CMV, HBV, Helicobacter pylori, Treponema pallidum, and Toxoplasma gondii). Tests were performed using the BioPlex 2200 or ELISA kits (Bio-Rad Laboratories, USA). We found a significant gradient of ANA positivity among the groups: 45% of Columbians, 38% of Kitavans, 26% of Mexicans, 12% of Italians, 12% of Dutch, and 11% of Israelis were ANA positive. Geographical differences were also observed regarding the prevalence of specific autoantibodies, namely ANA: anti-dsDNA, chromatin, SmRNP, Ro/SSA, La/SSB, Scl70; GI associated: antigliadin; and thrombophilia-associated: anti-β2GP1 and prothrombin. Additionally, significant differences were observed regarding serological markers of all infectious agents screened. The observed variance between healthy ethno-geographical distinct populations in prevalence of autoantibodies may represent different genetic or environmental (e.g., prior exposure to infection) influences. Thus may illuminate possible causes of geoepidemiological differences in AD.
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Affiliation(s)
- Yinon Shapira
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
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Shapira Y, Agmon-Levin N, Selmi C, Petríková J, Barzilai O, Ram M, Bizzaro N, Valentini G, Matucci-Cerinic M, Anaya JM, Katz BSP, Shoenfeld Y. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun 2012; 39:112-6. [PMID: 22297145 DOI: 10.1016/j.jaut.2012.01.001] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2012] [Accepted: 01/07/2012] [Indexed: 02/08/2023]
Abstract
The identification of etiological factors in the induction of autoimmunity has remained elusive despite an enormous effort at dissection of the molecular structure of the target antigens and effector mechanisms. One characteristic feature of autoantigens is their repetitive structure as well as their conservation and evolution. Toxoplasma (T.) gondii is a primitive protozoan. We hypothesized that patients with autoimmune disease would have broad reactions against Toxoplasma antigens based on autoantigen conservation. To address this issue, we assessed serologic evidence of reactivity to Toxoplasma gondii along with a large profile of autoantibodies in patients with various autoimmune diseases (AID). We included sera of 1514 patients with 11 different AID collected from referral centers in Europe and Latin America as well as from 437 geographically matched controls, for the prevalence of anti Toxoplasma antibodies (ATxA) IgG and IgM and serum autoantibodies utilizing the BioPlex 2200 system (Bio- Rad Laboratories, USA). Serum ATxA IgG were positive in 42% of patients with AID versus 29% of controls (p < 0.0001). Among Europeans, ATxA IgG were associated with anti-phospholipid syndrome (APS; p < 0.0001), cryoglobulinemia (p < 0.0001), ANCA-associated vasculitides (p < 0.01), autoimmune thyroid diseases (p < 0.0001), systemic sclerosis (SSc; p < 0.0001) and rheumatoid arthritis (RA; p < 0.0001). Of note, Latin American RA sera exhibited similar frequency of ATxA IgG as controls. ATxA IgM were more prevalent in European patients with APS (p < 0.01), SSc (p < 0.05) and inflammatory bowel disease (IBD, p < 0.05) than in controls. Further, in AID patients the presence of ATxA correlated with autoantibodies characteristic of APS (anti- cardiolipin, B2GPI, complex of cardiolipin- B2GPI, prothrombin, phosphatydilethanolamine), and of SSc (anti-centromere, Scl-70). Our findings suggest that T. gondii may contribute to the pathogenesis of AID. This interaction may depend on or explain observed geoepidemiological variance in AID.
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Affiliation(s)
- Yinon Shapira
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel
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Figura N, Franceschi F, Santucci A, Bernardini G, Gasbarrini G, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter 2010; 15 Suppl 1:60-8. [PMID: 21054655 DOI: 10.1111/j.1523-5378.2010.00778.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The possible role of Helicobacter pylori as a trigger for some extragastric diseases has been largely investigated in the last year. There are, in fact, several studies concerning cardiovascular diseases, neurological disorders, diabetes mellitus, ear and eyes diseases, immunological and hematological disorders, liver and bile tract diseases, gynecological and respiratory tract pathologies. Among them, idiopathic sideropenic anemia and idiopathic thrombocytopenic purpura still remain the extragastric diseases showing the most convincing results. Concerning ischemic heart disease, there are new interesting data playing in favor of the association, even though there are still some open issues to be clarified. For the other diseases, more studies are needed to clarify the reality of the proposed association.
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Affiliation(s)
- Natale Figura
- Internal Medicine Department, University of Siena, Largo A. Gemelli 8, Rome, Italy
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39
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Rojas-Villarraga A, Botello-Corzo D, Anaya JM. HLA-Class II in Latin American patients with type 1 diabetes. Autoimmun Rev 2010; 9:666-73. [DOI: 10.1016/j.autrev.2010.05.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2010] [Accepted: 05/17/2010] [Indexed: 12/28/2022]
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