Metabolically Healthy Obesity and the Risk of Erosive Esophagitis: A Cohort Study

OBJECTIVES: Obesity is an established risk factor of erosive esophagitis, and metabolic unhealthiness has been implicated in the pathogenesis of erosive esophagitis. Yet, the risk of erosive esophagitis among obese individuals without obesity-related metabolic unhealthiness, a condition referred to as "metabolically healthy obese (MHO)", remains unclear. We examined the association between body mass index (BMI) categories and the development of erosive esophagitis in a cohort of metabolically healthy individuals. METHODS: We conducted a cohort study of 14,725 asymptomatic adults free of erosive esophagitis and metabolic abnormalities, who underwent repeated health checkups including screening endoscopy. A metabolically healthy state was defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance <2.5. The presence of erosive esophagitis was determined using endoscopy. RESULTS: During 81,385.2 person-years of follow-up, 1,865 participants developed erosive esophagitis (incidence rate, 22.9 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident erosive esophagitis comparing overweight (BMI 23.0-24.9) and obese (≥25) with normal-weight participants (18.5-22.9) were 1.12 (1.00-1.25) and 1.29 (1.14-1.47), respectively. In dose-response analyses, increasing BMI also showed positive association with overall and LA-B grade or higher. The association persisted in MHO individuals without central obesity. The association between waist circumference categories and the development of erosive esophagitis was also evident. DISCUSSION: In a large cohort of strictly defined metabolically healthy men and women, the MHO phenotype was associated with an increased incidence of erosive esophagitis, providing evidence that the MHO phenotype is not protective from gastroesophageal reflux disease.