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Background: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections. H. pylori is one of the most common infection worldwide. Aim of the paper was to evaluate the prevalence of H. pylori infection, the efficacy of the most common H. pylori eradication therapies and the incidence of H. pylori reinfection after 12 months follow-up in IDDM and in a control group of dyspeptic patients matched for sex and age., Methods: 116 IDDM patients and 50 dyspeptic controls were evaluated for H. pylori infection through 13C-urea breath test (UBT). 64 IDDM infected patients and 50 dyspeptic infected controls were randomly assigned to 3 different 7-day eradication regimens: 1) amoxicillin, clarithromycin, pantoprazole; 2) tinidazole, clarithromycin, ranitidine bismuth citrate; 3) tinidazole, clarithromycin, pantoprazole. Patients not eradicated by the first cycle were subsequently submitted to a 7-day quadruple therapy with tinidazole, tetracycline, bismuth and pantoprazole. Gastrointestinal symptoms and side effects were evaluated. Thirty-four IDDM patients and 40 dyspeptic patients previously treated for H. pylori infection and successfully eradicated (confirmed both by UBT and histology) were re-evaluated after 12 months., Results: 37% of IDDM patients were infected. Mean age of IDDM infected patients was higher than negative (40+/-12 vs 32+/-10 yrs). None of the triple therapies used allowed an eradication higher than 62%. Conversely, the quadruple regimen eradicated 88% of patients. Minor side effects were observed in 10% of patients submitted to the triple therapies and in 25% of patients treated with the quadruple therapy (p<0.05). H. pylori re-infection was significantly higher in IDDM patients compared to controls: (38% vs 5% respectively, p<0.001). Mean age of IDDM re-infected patients was higher than negative (40+/-12 vs 32+/-10). Among IDDM patients daily insulin requirement and glicate haemoglobin were significantly higher in re-infected compared to uninfected patients (44+/-9 vs 35+/-8 U/I and 7,2+/-1 vs 6,8+/-0,8)., Conclusions: Prevalence of H. pylori infection in IDDM patients was similar to controls. IDDM patients show a low H. pylori eradication rate with a standard triple therapy regardless of the regimen utilized. The use of a quadruple regimen leads to the cure of a large percentage of the infected patients not eradicated by the first therapy, although it is accompanied by a greater incidence of minor side effects. A significantly higher incidence of H. pylori re-infection was observed in IDDM patients when compared to not IDDM controls. The data suggest that vaccine development seems to be the only effective long run treatment for this subset of patients.