Helycobacter

pyloriEmbargoed until 12.01A.M. EDT, Wednesday, March 14, 2012
MAJOR ARTICLE

Association Between Gastric Helicobacter pylori
Colonization and Glycated Hemoglobin Levels
Yu Chen1,2,3 and Martin J. Blaser3,4,5
1Department of Environmental Medicine, 2New York University Cancer Institute, 3Department of Medicine and 4Department of Microbiology, New York
University School of Medicine; and5Department of Veterans Affairs Medical Center, New York, New York

(See the editorial commentary by Cohen and Muhsen, on pages 1183–5.)

Background. Few studies have evaluated the potential influence of Helicobacter pylori on biomarkers for diabetes.
Methods. We conducted cross-sectional analyses using data from 7417 participants in the National Health and
Nutrition Examination Survey (NHANES)III (aged $18 years) and 6072 participants in NHANES 1999–2000
(aged $3 years) to assess the association between H. pylori and levels of glycosylated hemoglobin (HbA1c).
Results. There was no association between H. pylori and history of self-reported diabetes. Helicobacter pylori
seropositivity, especially H. pylori cagA positivity, was positively associated (P , .01, NHANES III; P 5 .02,NHANES 1999–2000) with HbA1c levels after excluding individuals with history of diabetes and controlling for
potential confounders. There was also a synergistic interaction between H. pylori and higher body mass index (BMI),
such that increased levels of HbA1c associated with having both H. pylori and higher BMI were greater than the sum
of their individual effects (P for interaction , .01). Thisinteraction was observed consistently in both NHANES III
and NHANES 1999–2000 and for H. pylori cagA positivity in NHANES III.
Conclusions. The findings indicate a role of H. pylori in impaired glucose tolerance in adults that may be
potentiated by higher BMI level.

Diabetes mellitus, a chronic disease marked by high
levels of sugar in the blood, is common and increasing
around the world [1].Although major risk factors for
type 2 diabetes, such as obesity, have been identified,
research that assesses susceptibility to diabetes risk due
to obesity is needed.
The mammalian stomach produces leptin and ghrelin, 2 hormones involved in energy homeostasis [2, 3]
and whose interactions affect obesity, insulin sensitivity, and glucose homeostasis [4, 5]. Helicobacter
pylori aregram-negative bacteria that colonize the
human stomach; increasing evidence indicates that
H. pylori is involved in the regulation of these 2 hormones [6]. Helicobacter pylori is an ancient organism

Received 16 August 2011; accepted 14 November 2011.
Correspondence: Yu Chen, PhD, Departments of Environmental Medicine and
Medicine, New York University School of Medicine, 650 First Ave, New York, NY10016 (yu.chen@nyumc.org).
The Journal of Infectious Diseases 2012;205:1195–202
Ó 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/jis106

that is highly prevalent in developing countries but is
falling in incidence in developedcountries [7, 8]. This
change in the microecology of human populations
due to the disappearance of H. pylori may have metabolic consequences both early and late in life and, in
particular, could affect risk of obesity and diabetes
by influencing the production of gastric leptin and
ghrelin [6].
The literature on the relationship between H. pylori
colonization and diabetes is inconsistent[9–15]. To
better understand the pathophysiologic mechanisms by
which H. pylori plays a role in diabetes etiology, studies
of diabetes biomarkers are needed. Glycated hemoglobin
(HbA1c) results from the nonenzymatic glycosylation of
hemoglobin, reflecting integrated blood glucose levels
during the preceding 3–4 months [16–18]; as such,
fasting is not necessary for its measurement. HbA1c...