Abstract
BACKGROUND & AIMS: Central obesity could increase the risk for Barrett's esophagus (BE) and esophageal adenocarcinoma by mechanical and/or metabolic mechanisms, such as hyperinsulinemia. We performed an epidemiologic study to determine whether prior type 2 diabetes mellitus (DM2) is associated with BE. METHODS: We performed a population-based case-control study using the General Practice Research Database, a UK primary care database that contains information on more than 8 million subjects, to identify cases of BE (using previously validated codes; n = 14,245) and matched controls without BE (by age, sex, enrollment date, duration of follow-up evaluation, and practice region by incidence density sampling; n = 70,361). We assessed the association of a prior diagnosis of DM2 with BE using conditional univariate and multivariable regression analysis. Confounders assessed included smoking, obesity measured by body mass index (BMI), and gastroesophageal reflux disease. RESULTS: BE cases were more likely than controls to have smoked (52.4% vs 49.9%), have a higher mean BMI (27.2 vs 26.9), and a higher prevalence of DM2 than controls (5.8% vs 5.3%). On multivariable analysis, DM2 was associated with a 49% increase in the risk of BE, independent of other known risk factors (odds ratio, 1.49; 95% confidence interval, 1.16-1.91). This association was stronger in women than men. Results remained stable with sensitivity analyses. CONCLUSIONS: In a large population-based case-control study, DM2 was a risk factor for BE, independent of obesity (as measured by BMI) and other risk factors (smoking and gastroesophageal reflux disease). These data suggest that metabolic pathways related to DM2 should be explored in BE pathogenesis and esophageal carcinogenesis.