Helicobacter pylori eradication in diabetic patients: still far off the treatment targets.

Over 25 years after Barry and Marshall first linked it with peptic ulcer disease, Helicobacter pylori (HP) remains one of the most common infections worldwide. HP is associated with gastrointestinal problems ranging from simple non-ulcer dyspepsia to uncomplicated or complicated (perforation or bleeding) peptic ulcer disease, mucosa-associated lymphatic tissue (MALT) lymphoma disease, and gastric adenocarcinomas. Extraintestinal manifestations of HP include iron deficiency anemia and idiopathic thrombocytopenic purpura. Detection of HP can be achieved endoscopically by rapid urease testing, histology, or culture. Non-endoscopic methods include serological antibody testing, 14C-labeled urea breath test (UBT), and fecal antigen testing. The Maastricht III Consensus and the American College of Gastroenterology guidelines both recommend that HP eradication therapy should yield a success rate of 80%. Antimicrobial resistance is, however, a major problem, and clarithromycin resistance can be found in 4–40% of patients. Other predictors of poor outcome include non-adherence, smoking, alcohol consumption, and CagA-negative strains of HP. In routine clinical practice, these factors are either difficult to ascertain (antimicrobial resistance, CagA status) or difficult to influence (non-adherence, smoking, and alcohol). The issue of outcomes of attempted HP eradication in diabetic patients has long been neglected in the medical literature, and does not feature in the relevant guidelines. Recent studies have shown that standard triple therapy HP eradication regimens lead to eradication rates of 62% in type 1 diabetes mellitus (DM) patients, and 50% in type 2 DM patients. As these eradication rates clearly fail to meet the advised success rate of 80%, there is an urgent need for eradication regimes leading to better success rates in diabetic patients. Ataseven et al have tested a sequential regimen of pantoprazole and amoxicillin, followed by pantoprazole, metronidazole, and tetracycline. The rationale behind this approach was based on a meta-analysis that found sequential therapy superior to standard triple therapy when treating patients with Helicobacter pylori. However, Ataseven et al’s open-label trial of sequential therapy had a success rate of just under 60% in a cohort of patients suffering from type 2 diabetes. This is in line with standard triple therapy results in diabetic patients, hence sequential therapy is no better than the established regimens. Currently there is no regimen of HP eradication that has been shown to have an acceptable success rate in patients with type 2 diabetes. Where do these results leave primary and secondary care physicians caring for type 2 DM patients with HP? First of all, the focus should be on the degree of need to eradicate HP. While active peptic ulcer disease and gastric MALT lymphomas are absolute indications for HP eradication, the role of HP eradication remains controversial in indications such as non-ulcer dyspepsia, gastroesophageal reflux disease, and unexplained iron deficiency anemia. Patients who would normally undergo testing and treatment for uninvestigated dyspepsia could be investigated with an endoscopy to stratify them by risk, rather than be treated with a regimen that does not work 50% of the time. Secondly, when the need for HP eradication has been established in patients with type 2 DM, the success of eradication should be evaluated. The Maastricht III Consensus suggests 14C-urea breath testing for all patients after HP eradication, but the American guidelines find this approach neither practical nor cost-effective. In patients with type 2 DM, however, we feel the anticipated low success rate of eradication makes UBT worthwhile. Efforts should be made to achieve and prove HP eradication when the indication for it is strong, but in cases of controversial indications, the decision whether to attempt eradication should be based on the balance of likelihood of success and the likelihood of success leading to symptomatic improvement for the individual patient.