Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Commentaries

Stomach Bugs and Diabetes: An Astounding Observation or Just Confounding?

  1. Christopher K. Rayner, MBBS, PHD1,2⇓,
  2. Nicholas J. Talley, MD, PHD3 and
  3. Michael Horowitz, MBBS, PHD1,2
  1. 1University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia; the
  2. 2Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, Australia; and the
  3. 3Faculty of Health, University of Newcastle, Callaghan, Australia
  1. Corresponding author: Christopher K. Rayner, chris.rayner{at}adelaide.edu.au.
Diabetes Care 2012 Mar; 35(3): 463-464. https://doi.org/10.2337/dc11-2470
  • Article
  • Info & Metrics
  • PDF
Loading

The discovery that a Gram-negative spiral bacillus was responsible for most peptic ulcer disease (1) created a paradigm shift that culminated in Marshall and Warren being awarded the Nobel Prize in Physiology or Medicine for 2005. Helicobacter pylori induces inflammation that may be limited to the gastric antrum, or can involve the corpus with subsequent mucosal atrophy, and is characterized, particularly in those strains that are positive for cytotoxin-associated gene A, by induction of cytokines including interleukins (IL-) 1, 6, and 8, and tumor necrosis factor-α (2). H. pylori is an established risk factor for gastric adenocarcinoma and lymphoma arising from mucosa-associated lymphoid tissue (MALT).

H. pylori appears to be acquired mainly in childhood by the fecal-oral or gastro-oral route. In developing countries, 80% or more of the population are infected by 20 years of age, while in the developed world the prevalence of infection increases with age. In each subsequent cohort, improving socioeconomic conditions lead to lower rates of infection in childhood (3). In Australia, for example, seroprevalence was recently estimated at ∼30% for those ≥70 years of age, but only 5% for those <40 years of age (4).

Over the last 15–20 years, an increased prevalence of diverse diseases, including coronary artery (5) and cerebrovascular (6) disease, Alzheimer disease, migraine, Raynaud phenomenon, and chronic urticaria (7), has been reported in those with evidence of H. pylori infection. Plausible explanations to account for these associations include infection-induced systemic inflammation with increased “oxidative stress” and molecular mimicry (for example, between H. pylori and endothelial antigens) (7). However, many studies have potentially been biased, particularly when control groups were recruited opportunistically, and it is not always clear that appropriate adjustment has been made for confounders like age and socioeconomic status. For example, in relation to coronary artery disease, when a socioeconomically homogeneous sample such as from the Physicians’ Health Study was examined, no increased risk of future myocardial infarction was evident among those seropositive for H. pylori (8). Currently, none of these putative associations is widely accepted as causally linked (9).

In this month’s issue of Diabetes Care, Jeon et al. (10) report their analysis of a Latino cohort from the Sacramento, California, area. They followed 782 people aged ≥60 years twice yearly for a decade; participants were not known to have diabetes at entry and had serum assayed for antibodies to H. pylori, herpes simplex virus 1 (HSV-1), varicella zoster virus, cytomegalovirus (CMV), and Toxoplasma gondii, as well as inflammatory markers (IL-6 and C-reactive protein [CRP]), lipids, glucose, and insulin. During follow-up, 144 individuals developed diabetes (presumably type 2), with the rate being more than double in those who were seropositive for H. pylori at entry compared with the seronegative, even after adjusting for age, sex, education, and covariates such as smoking, BMI, blood pressure, and lipids. In contrast, antibodies to the other infectious agents were not associated with an increased risk of developing diabetes, nor was H. pylori seropositivity associated with higher concentrations of IL-6 or CRP. As expected, the presence of insulin resistance (evaluated by homeostasis model assessment [HOMA-IR]) predicated subsequent diabetes; however, HOMA-IR was not related to H. pylori status.

Simon at al. (11) were the first to report an association between H. pylori infection and type 2 diabetes, and positive reports have subsequently come from groups in the Netherlands (12), Italy (13), Turkey (14), and Africa (15). These all have significant methodological limitations, including small sample sizes, case-control designs, recruitment from clinical populations, and potential for socio-demographic confounding. Moreover, other studies have been unable to substantiate the association (16,17), while the largest study (1,000 individuals from ethnically diverse U.S. communities) (18) found that an apparent higher prevalence of diabetes in those seropositive for H. pylori, CMV, hepatitis A, and HSV became nonsignificant after adjustment for demographic covariates.

The strength of the study of Jeon et al. is its prospective nature. However, the rate of seropositivity to H. pylori was extraordinarily high (over 90%), so there were few seronegative individuals; no information is provided regarding the sensitivity and specificity of the assay. Furthermore, serology cannot distinguish current from previous infection, and the proportion of subjects previously given eradication therapy is unknown. Residual confounding (for example, by socioeconomic factors) cannot be excluded, and the mechanism by which H. pylori infection could predispose to diabetes remains unclear, particularly as there were no increases in the markers of systemic inflammation that were examined. Several reports have linked H. pylori infection to insulin resistance (19,20), but the HOMA-IR did not differ with H. pylori status in the current study, and an association between H. pylori seropositivity and insulin resistance is not supported by analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) (21). Jeon et al. suggest that changes in gastric emptying could adversely affect glycemia, but delayed gastric emptying is a potential advantage, rather than a disadvantage, in relation to glycemic control in type 2 diabetic patients not treated with insulin (22); moreover, H. pylori has been shown not to affect the rate of gastric emptying in patients with diabetes (23). H. pylori-induced gastritis can potentially affect the secretion of “gastric” hormones including leptin and ghrelin (24), which might feasibly predispose to diabetes. Whether H. pylori could induce a defect in insulin secretion remains speculative. Type 2 diabetes would seem highly unlikely to predispose to H. pylori infection given the age at which the latter is usually acquired.

It would be premature to advocate an aggressive test-and-treat strategy for H. pylori in those at risk for developing type 2 diabetes on the basis of the current evidence. Demonstrating that such an intervention would reduce the subsequent incidence of diabetes would require a very large, long-term prospective study given that any effect is likely to be relatively small. Universal attempts to eradicate H. pylori carry concomitant risks of drug-related morbidity and antibiotic resistance, although it is likely that infection rates will continue to decline in developing countries as socioeconomic status improves. Currently accepted indications to test for H. pylori include active, or previous, peptic ulcer disease, gastric MALT lymphoma, early gastric cancer, and “uninvestigated” dyspepsia (9); the latter applies to younger patients without “alarm features” for malignancy. Diabetes is itself associated with an increased prevalence of gastrointestinal symptoms, including dyspepsia (25), but the presence of symptoms in diabetes has not consistently been shown to relate to H. pylori status (17). Meta-analyses indicate a small, but statistically significant, benefit in eradicating H. pylori in nonulcer dyspepsia in the general population (9), but there is insufficient evidence as to whether this applies to patients with diabetes.

Acknowledgments

No potential conflicts of interest relevant to this article were reported.

  • © 2012 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

References

  1. ↵
    1. Marshall BJ,
    2. Warren JR
    . Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311–1315pmid:6145023
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    1. Moss SF,
    2. Legon S,
    3. Davies J,
    4. Calam J
    . Cytokine gene expression in Helicobacter pylori associated antral gastritis. Gut 1994;35:1567–1570pmid:7828974
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Malaty HM
    . Epidemiology of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol 2007;21:205–214pmid:17382273
    OpenUrlCrossRefPubMed
  4. ↵
    1. Pandeya N,
    2. Whiteman DC;,
    3. Australian Cancer Study
    . Prevalence and determinants of Helicobacter pylori sero-positivity in the Australian adult community. J Gastroenterol Hepatol 2011;26:1283–1289pmid:21443663
    OpenUrlCrossRefPubMed
  5. ↵
    1. Mendall MA,
    2. Goggin PM,
    3. Molineaux N,
    4. et al
    . Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J 1994;71:437–439pmid:8011406
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Markus HS,
    2. Mendall MA
    . Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma. J Neurol Neurosurg Psychiatry 1998;64:104–107pmid:9436737
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Gasbarrini A,
    2. Franceschi F,
    3. Armuzzi A,
    4. et al
    . Extradigestive manifestations of Helicobacter pylori gastric infection. Gut 1999;45Suppl. 1I9–I12pmid:10457029
    OpenUrlFREE Full Text
  8. ↵
    1. Ridker PM,
    2. Danesh J,
    3. Youngman L,
    4. et al
    . A prospective study of Helicobacter pylori seropositivity and the risk for future myocardial infarction among socioeconomically similar U.S. men. Ann Intern Med 2001;135:184–188pmid:11487485
    OpenUrlPubMed
  9. ↵
    1. Chey WD,
    2. Wong BC;,
    3. Practice Parameters Committee of the American College of Gastroenterology
    . American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007;102:1808–1825pmid:17608775
    OpenUrlCrossRefPubMedWeb of Science
  10. ↵
    1. Jeon CY,
    2. Haan MN,
    3. Cheng C,
    4. et al
    . Helicobacter pylori infection is associated with an increased rate of diabetes. Diabetes Care 2012;35:520–525pmid:9538986
    OpenUrlPubMed
  11. ↵
    1. Simon L,
    2. Tornóczky J,
    3. Tóth M,
    4. Jámbor M,
    5. Sudár Z
    . The significance of Campylobacter pylori infection in gastroenterologic and diabetic practice. Orv Hetil 1989;130:1325–1329 [in Hungarian]pmid:2664637
    OpenUrlPubMed
  12. ↵
    1. Oldenburg B,
    2. Diepersloot RJ,
    3. Hoekstra JB
    . High seroprevalence of Helicobacter pylori in diabetes mellitus patients. Dig Dis Sci 1996;41:458–461pmid:8617115
    OpenUrlCrossRefPubMedWeb of Science
  13. ↵
    1. Quadri R,
    2. Rossi C,
    3. Catalfamo E,
    4. et al
    . Helicobacter pylori infection in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 2000;10:263–266pmid:11213535
    OpenUrlPubMed
  14. ↵
    1. Gulcelik NE,
    2. Kaya E,
    3. Demirbas B,
    4. et al
    . Helicobacter pylori prevalence in diabetic patients and its relationship with dyspepsia and autonomic neuropathy. J Endocrinol Invest 2005;28:214–217pmid:15952404
    OpenUrlPubMedWeb of Science
  15. ↵
    1. Longo-Mbenza B,
    2. Nkondi Nsenga J,
    3. Vangu Ngoma D
    . Prevention of the metabolic syndrome insulin resistance and the atherosclerotic diseases in Africans infected by Helicobacter pylori infection and treated by antibiotics. Int J Cardiol 2007;121:229–238pmid:17368586
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    1. Dore MP,
    2. Bilotta M,
    3. Malaty HM,
    4. et al
    . Diabetes mellitus and Helicobacter pylori infection. Nutrition 2000;16:407–410pmid:10869894
    OpenUrlCrossRefPubMedWeb of Science
  17. ↵
    1. Xia HH,
    2. Talley NJ,
    3. Kam EP,
    4. Young LJ,
    5. Hammer J,
    6. Horowitz M
    . Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol 2001;96:1039–1046pmid:11316144
    OpenUrlCrossRefPubMedWeb of Science
  18. ↵
    1. Lutsey PL,
    2. Pankow JS,
    3. Bertoni AG,
    4. Szklo M,
    5. Folsom AR
    . Serological evidence of infections and type 2 diabetes: the MultiEthnic Study of Atherosclerosis. Diabet Med 2009;26:149–152pmid:19236617
    OpenUrlCrossRefPubMed
  19. ↵
    1. Aydemir S,
    2. Bayraktaroglu T,
    3. Sert M,
    4. et al
    . The effect of Helicobacter pylori on insulin resistance. Dig Dis Sci 2005;50:2090–2093pmid:16240220
    OpenUrlCrossRefPubMed
  20. ↵
    1. Gunji T,
    2. Matsuhashi N,
    3. Sato H,
    4. et al
    . Helicobacter pylori infection significantly increases insulin resistance in the asymptomatic Japanese population. Helicobacter 2009;14:144–150pmid:19751440
    OpenUrlPubMed
  21. ↵
    1. Gillum RF
    . Infection with Helicobacter pylori, coronary heart disease, cardiovascular risk factors, and systemic inflammation: the Third National Health and Nutrition Examination Survey. J Natl Med Assoc 2004;96:1470–1476pmid:15586651
    OpenUrlPubMed
  22. ↵
    1. Chang J,
    2. Rayner CK,
    3. Jones KL,
    4. Horowitz M
    . Diabetic gastroparesis and its impact on glycemia. Endocrinol Metab Clin North Am 2010;39:745–762pmid:21095542
    OpenUrlCrossRefPubMed
  23. ↵
    1. Jones KL,
    2. Wishart JM,
    3. Berry M,
    4. et al
    . Helicobacter pylori infection is not associated with delayed gastric emptying or upper gastrointestinal symptoms in diabetes mellitus. Dig Dis Sci 2002;47:704–709pmid:11991596
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    1. Roper J,
    2. Francois F,
    3. Shue PL,
    4. et al
    . Leptin and ghrelin in relation to Helicobacter pylori status in adult males. J Clin Endocrinol Metab 2008;93:2350–2357pmid:18397989
    OpenUrlCrossRefPubMedWeb of Science
  25. ↵
    1. Bytzer P,
    2. Talley NJ,
    3. Leemon M,
    4. Young LJ,
    5. Jones MP,
    6. Horowitz M
    . Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med 2001;161:1989–1996pmid:11525701
    OpenUrlCrossRefPubMedWeb of Science
Back to top
Diabetes Care: 44 (3)

Current Issue

March 2021
Volume 44, Issue 3

  • Current Issue
  • Index by Author
  • Issue Archive
  • Podcasts
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Stomach Bugs and Diabetes: An Astounding Observation or Just Confounding?
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Stomach Bugs and Diabetes: An Astounding Observation or Just Confounding?
Christopher K. Rayner, Nicholas J. Talley, Michael Horowitz
Diabetes Care Mar 2012, 35 (3) 463-464; DOI: 10.2337/dc11-2470

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Stomach Bugs and Diabetes: An Astounding Observation or Just Confounding?
Christopher K. Rayner, Nicholas J. Talley, Michael Horowitz
Diabetes Care Mar 2012, 35 (3) 463-464; DOI: 10.2337/dc11-2470
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Acknowledgments
    • References
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Apps and the Woman With Gestational Diabetes Mellitus
  • The Prognostic Value of Time in Range in Type 2 Diabetes
  • Spontaneous or Deliberate: Effects of Acute Variations in Glycemia on Gastric Emptying in Type 1 Diabetes
Show more Commentaries

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.