This study provided for the first time a nation-wide population-based analysis with a large sample size on the association between T2DM and HP eradication. Diabetes was significantly associated with a higher incidence of HP eradication (Tables , , ), independent of comorbidities, medications, PES, occupation and living region (Tables and ). The odds ratios attenuated with increasing diabetes duration, probably due to the increased occurrence of comorbidities, which might also affect the incidence of HP eradication (Table ). Furthermore, use of calcium channel blockers (Table ) and insulin use in the diabetic patients (Tables , , ) were also significantly associated with HP eradication.
The higher incidence of HP eradication associated with diabetes could be explained by the following possibilities: the diabetic patients might have a higher chance of being detected for HP infection, or they might have a higher HP infection rate or a higher activity of HP infection. A higher detection rate is possible because the diabetic patients were more prone to have PES (Table ). However, this could not explain the whole picture because the higher incidence of HP eradication associated with diabetes remained significant after adjustment for PES and other covariates (Tables and ). Currently we do not have HP infection rates in Taiwanese diabetic and non-diabetic subjects. Some studies suggested that the HP infection rates are similar between non-diabetic and diabetic subjects in patients with either T1DM [3
] or T2DM [12
]. If this is the case, the higher incidence of HP eradication associated with diabetes (Tables ) may implicate that HP infection in the diabetic patients is more clinically active with more severe symptoms, leading to its diagnosis and the use of medications for its eradication.
Insulin use was consistently associated with a higher incidence of HP eradication, but none of the oral anti-diabetic agents was (Tables ). Insulin use may be a proxy for uncontrollable hyperglycemia with more severe disease. Therefore this observation might be explained in the following ways. HP infected patients might have deteriorated metabolic control [8
] and required insulin therapy; or they might have more severe diabetic conditions (e.g., diabetic gastroparesis) with gastrointestinal symptoms leading to more aggressive examination and diagnosis of HP infection.
A significantly higher rate of HP eradication was seen in subjects taking calcium channel blockers (Table ). It is interesting that calcium channel blockers are also associated with gastroesophageal reflux disease, probably due to its relaxation effect on lower esophageal sphincter [15
]. HP infection can induce pepsinogen release from chief cells (which may induce and aggravate peptic ulcer disease) via mechanisms involving calcium and calmodulin [16
]. However, L-type calcium channel is not responsible for the pepsinogen release induced by HP [16
]. Therefore it is unlikely that calcium channel blockers used in clinical practice would affect the peptic ulcers induced by HP. It was possible that the gastrointestinal symptoms associated with its use that led to the diagnosis of HP infection.
Recent studies suggest that HP eradication may reverse atrophic gastritis and improve intestinal metaplasia, which may contribute to the reduction of gastric cancer occurrence [17
]. Therefore, early diagnosis of HP infection with clinical use of medications to eradicate the infection is not only important for the treatment of the clinical symptoms related to the infection, but also for the prevention of gastric cancer. One clinical implication of the present study is that patients with T2DM, especially those treated with insulin, may belong to a high risk group requiring special medical attention.
HP infection rate in a community-based study in Taiwan was 54.4%, and it showed age-dependency without sexual difference [20
]. Although the present study suggested that clinical presentation of HP eradication was age-dependent (Tables and ), it also demonstrated a higher incidence of HP eradication in the male population (Tables and ). The reasons for a higher risk of HP eradication in men are still unknown. One possibility is that the activity of HP infection could be higher in men, which is correspondent to the higher risk of gastric cancer in men than in women in Taiwan [1
Except for eye disease, obesity and dyslipidemia (in diabetic patients only) all other comorbidities were significantly associated with HP eradication (Table ). This observation explained the attenuated odds ratios with prolonged diabetes duration (Table ), when chronic complications might set in and interfere with the association between diabetes and HP eradication.
Some studies suggested that people living in crowded condition or with lower socioeconomic status may have a higher risk of HP infection [21
]. In Taiwan, Taipei City is the most populated area. However, residents in relatively sparse area of Central Taiwan had significantly higher incidence of HP eradication than people living in other regions (Table ). This suggested that living in crowded condition might not be an important predisposing factor. On the other hand, people with an occupation as farmers or fishermen (occupation III) or with low family income (occupation IV) consistently showed significantly higher odds ratios (Table ), suggesting a possible role of socioeconomic status or its related condition of hygiene.
This study has several strengths. It is population-based with a large nationally representative sample, therefore, the study is not likely to be biased with respect to diabetes status or records of HP eradication. Because NHI is a universal and mandatory insurance with very high coverage but low co-payments, the detection rate would not tend to differ among different social classes.
Limitations included a lack of actual measurement of some recognized confounders such as personal hygiene, living condition, blood groups and genetic factors. We also did not have biochemical data including blood glucose, hemoglobin A1c
and lipid profiles to evaluate whether HP infection can affect metabolic control. This study evaluated the incidence of HP eradication and not the prevalence or incidence of HP infection. However, because most people infected with HP do not develop clinical disease [21
], estimation of prevalence or incidence of HP infection may not have clinical relevance as the evaluation of HP eradication does. Another concern is that there might be considerable under-diagnosis and under-treatment of HP infection. However, if the misclassification of the outcome is non-differential, an underestimation of the odds ratios is expected.