Association Between Helicobacter pylori Colonization and Glycated Hemoglobin Levels: Is This Another Reason to Eradicate H. pylori in Adulthood?

Abstract

Helicobacter pylori infection is acquired in early childhood and becomes a chronic infection if left untreated [1]. The majority of infected people remain asymptomatic, and only a small portion develop illness, usually in adulthood [2]. Helicobacter pylori infection causes gastric and duodenal ulcers. It also increases the risk of gastric cancer [2, 3]; the bacterium was classified by the International Agency for Research on Cancer as a group 1 (definite) carcinogen in gastric carcinoma [4]. Helicobacter pylori also increases the likelihood of gastric lymphoma [5]. Moreover, positive associations between H. pylori infection and extragastric manifestations, such as iron deficiency anemia [6] and idiopathic thrombocytopenic purpura, also have been reported [7]. Many of the above-mentioned diseases and conditions are associated with the primary H. pylori virulence factors, cytotoxin-associated gene A (cagA) and vacuolating-associated gene A (vacA). Chronic H. pylori infection causes a continuous activation of the immune system, with a skewed T-helper 1 response [8, 9]. This response has been proposed as a possible mechanism responsible for some potential beneficial effects of H. pylori infection, such as protection against diarrheal diseases [10] and asthma [11]. Type 2 diabetes is an emerging pandemic, with estimates of 3.8 million deaths attributed to the disease in adults globally [12]. Lifestyle (eg, diet, obesity, physical activity), genetic, and socioeconomic factors are among the risk factors for the disease [13, 14]. There are conflicting reports concerning the association between H. pylori infection and the various clinical manifestations of the metabolic or insulin-resistance syndrome [15]. The roles of H. pylori infection in cardiovascular disease and its risk factors [16–18] and in type 2 diabetes are not clear. Although no association was found between H. pylori immunoglobulin G seropositivity and diabetes mellitus [19], a significantly higher prevalence of H. pylori gastritis was reported in patients with type 2 diabetes, compared with age-matched healthy controls (80% vs 56%; P5 .03) [20]. A recent systematic review summarized the epidemiological evidence concerning the association between H. pylori infection and quantitative indexes of insulin resistance and indicated that such an association may exist. The authors of the review concluded, however, that further studies are needed to determine whether this is a causal association [15]. Studying biomarkers of diabetes mellitus, such as glycated hemoglobin levels (HbA1c) and insulin resistance, can contribute substantially to an understanding of the etiologic role of H. pylori infection in diabetes mellitus. In this issue of the Journal, Chen and Blaser report findings of a seroepidemiological study in which they examined the association between seroprevalence of H. pylori infection and the mean levels of HbA1c in 2 large national surveys: the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999–2000. They report that H. pylori seropositivity, and especially H. pylori cagA positivity, was associated with higher mean HbA1c levels, an association that persisted after excluding individuals with a history of diabetes mellitus and controlling for potential confounders. The association was evident mainly in adults aged .18 years. Chen and Blaser also show a synergistic effect of H. pylori and body mass index (BMI) on increased levels of HbA1c in that higher levels were found in H. pylori–infected subjects with BMI $25 but not in those with lower Received and accepted 4 January 2012. Correspondence: Dani Cohen, MPH, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel (dancohen@post.tau.ac.il). The Journal of Infectious Diseases The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com DOI: 10.1093/infdis/jis110