Selected studies that addressed associations of
Abstract
Helicobacter pylori colonizes the stomach and causes chronic gastritis, which most often remains asymptomatic. However, in a small proportion of infected persons, it causes peptic ulcers and gastric cancer. We reviewed recent evidence of the association between H. pylori infection and diabetes mellitus (DM). Numerous studies have shown a positive association between H. pylori infection and DM, however, findings are still conflicting. Such a link is biologically plausible, given the importance of the stomach in the homeostasis of systems outside the digestive tract; however, the mechanisms by which H. pylori might affect the risk of DM are not clear. Current knowledge indicates that H. pylori infection can affect the regulation of ghrelin and leptin, two hormones that play central roles in energy homeostasis in humans. Yet, methodological limitations are present in studies that addressed the relationships of H. pylori infection with DM and with possible risk factors for DM, including inadequate control of confounders. The important question of whether H. pylori eradication might be beneficial for glycemic control in diabetic patients is still unresolved. Future well-designed studies are needed to address these research questions, which are of clinical and great public health significance.
Keywords
- Helicobacter pylori
- diabetes mellitus
- epidemiology
1. Introduction
Following
Several studies have shown associations between
2. H. pylori infection, changes in gastric physiology and metabolic hemostasis
Although the role of
In addition,
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Isomoto et al. [44] |
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↓ | ↓ | ND | ND |
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NS | NS | ND | ND | |
Chuang et al. [46] |
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Males: ↓ Females: NS |
ND | NS | ND |
Jun et al. [52] |
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NS | NS | NS | ↑ |
Nishi et al. [53] |
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ND | ND | NS | ↑ |
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ND | ND | NS | ||
Francois et al. [45] |
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NS | ND | NS | ND |
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Pre-meal: NS Post meal: ↑ |
ND | ↑ | ND | |
Azuma et al. [47] |
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ND | ND | ↑ | |
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ND | ND | NS | ↓ | |
Jang et al. [54] |
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NS | ↑ | NS | ND |
Roper et al. [41] |
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NS | Fundic: NS Antral: NS Gastric juice:↑ |
↓ | Fundic: NS Antral:↓ |
Breidert et al. [43] |
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ND | ND | NS | Antrum: NS Corpus:↑ |
Altogether, these studies suggest that
3. H. pylori infection and diabetes mellitus
DM refers to a group of metabolic disorders that manifest with hyperglycemia. DM is classified based on the pathogenic course that results in hyperglycemia, with two broad categories designated as type 1 DM (T1DM) and type 2 DM (T2DM). T1DM is the result of interaction among genetic, environmental and immunological factors that eventually leads to destruction of beta cells in the pancreas and complete or near-complete insulin deficiency. T2DM consists of various disorders with variable levels of insulin resistance, impaired insulin secretion and increased glucose production. T1DM usually occurs in childhood and adolescence, and comprises 5–10% of all DM cases [55]. T2DM typically develops in adulthood and is responsible for the majority (90–95%) of DM cases [55].
DM is a major public health problem [56–60], causing an enormous burden to patients and their families, as well as to health care systems. The prevalence of T2DM is increasing globally [56–60] due to increases in life expectancy and obesity [56, 58]. It is estimated that 240 million people have T2DM, and that in 2025 about 380 million will have the disease, while 418 million will have impaired glucose tolerance (IGT) [56]. The burden of DM is amplified given its significant macro and microvascular complications (such as cardiovascular disease, kidney disease), in addition to peripheral neuropathy [55].
There are well-established risk factors for T2DM [61–67], including sociodemographic factors [64, 68, 69], lifestyle factors (e.g., obesity, physical inactivity, poor diet [61–67]) and high glucose levels reflecting IGT [65, 66]. Changes in diet (i.e., higher consumption of whole grain products and exchanging unsaturated fat for saturated fat), and in particular physical activity and avoidance of obesity, can prevent T2DM through changes in body fat and other mechanisms [61, 67, 70–72]. These may reduce the incidence of DM by 28–59% [72]. Such interventions are also important for better control of diabetes [70, 73]. Current evidence suggests that there must be additional factors besides lifestyle that contribute to the occurrence of DM.
In addition to the association mentioned above, between
Associations of
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Jeon et al. [30] California |
Age >60 years |
Prospective cohort | Serum IgG by ELISA |
DM | Adjusted HR 2.69 (95% CI: 1.10–6.60) | Sex, education, smoking, cholesterol, DBP, HSV-1 |
Hsieh et al. [86] Taiwan |
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Cross-sectional | Gastric biopsy: culture, histology and rapid urease test | T2DM | OR 1.67 (95% CI: 1.19–2.35) | |
Chen and Blaser [81] USA |
Data from NHANES III NHANES 1999–2000 |
Cross-sectional | Serum IgG by ELISA |
DM | NHANES 1999–2000: Adjusted OR: 1.30 (95% CI: 0.94–1.80) BMI>25 OR (1.43; 95% CI: 1.00–2.03) NHANES III: Adjusted OR: 0.99 (95% CI: 0.80–1.23) |
Age, sex, race, BMI, smoking, education |
El-Eshmawy et al. [111] Egypt |
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Case-control | Serum IgG and IgA by ELISA | T1DM | OR 3.67 (95% CI: 2.07–6.55) | Matching by age, sex, SES |
Longo-Mbenza et al. [91] Democratic Republic of the Congo |
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Prospective cohort Follow-up 9.6±0.8 years |
Serum IgG by ELISA |
DM | OR: 0.97 (95% CI: 0.35–2.86) | |
Xia et al. [89] Australia |
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Case-control | Serum IgG by ELISA |
T1DM T2DM |
Overall 0.94 (95% CI: 0.65–1.39) T2DM: OR: 1.03 (95% CI: 0.71–1.52) T1DM: OR: 0.40 (95% CI: 0.15–0.94) |
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Demir et al. [90] Turkey |
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Case-control | Gastric biopsy: rapid urease test and histology | T2DM | OR: 1.15 (95% CI: 0.71–1.85) | |
Colombo et al. [112] Italy |
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Case-control | Serum IgG and IgA by ELISA | T1DM | OR: 0.87 (95% CI: 0.52–1.46) | Matching by age |
Cenerelli et al. [92] Italy |
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Case-control | UBT | T2DM | OR: 1.06 (95% CI: 0.41–2.76) | |
Dore et al. [87] |
(ages 12–75 years) |
Case-control | Serum IgG by ELISA |
T1DM T2DM |
T1DM: 0.59 (95%CI: 0.40–0.87) T2DM: 2.08 (95%CI: 1.52–2.85) |
In stratified analysis by age group, SES, the differences were not significant |
Lutsey et al. [88] |
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Cross-sectional | Serum IgG by ELISA |
DM | Crude OR: 1.65 (95%CI: 1.16–2.34) Adjusted OR: 1.12 (0.78–1.62) |
Age, sex, rate, education and site |
4. H. pylori infection and glycemic control among diabetic patients
Given the observed associations between
The question of whether
5. H. pylori infection and metabolic syndrome
Metabolic syndrome is a cluster of metabolic risk factors that are associated with increased risk for atherosclerotic cardiovascular disease, T2DM and their complications. These factors include atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, increases small low-density lipoproteins [LDL], and low concentration of high-density lipoproteins [HDL]), elevated blood pressure and elevated fasting glucose levels known as impaired fasting glucose (IFG) or prediabetes [102, 103], which lead to a prothrombotic and proinflammatory state. The main risk factors for metabolic syndrome include obesity, mainly abdominal obesity and insulin resistance [103], as well as aging, physical inactivity and diet rich with saturated fat and cholesterol [103].
Recent studies have tested the hypothesis of a positive association between
The evidence from epidemiological studies on the association between
A recent large cross-sectional study conducted among 3578 persons aged 18–64 years from Taiwan has demonstrated that
A population-based study conducted among adults aged 25 years or over in Iran also reported a 1.5-fold significantly increased prevalence of metabolic syndrome (according to NCEP-ATP-III criteria) among
Gunji et al. [106], in a well-designed study carried out among 5488 Japanese men (mean age 47± 5 years) and 1906 women (mean age 46±4 years), demonstrated a significant positive relationship between
While there is a growing compelling evidence from large epidemiological studies supporting the existence of a positive association between
6. Conclusions and future directions
Current evidence is conflicting regarding the question of whether
Addressing these research questions is of great public health and clinical significance given the high prevalence of
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