2023 Impact Factor
2023 Impact Factor
,1 Yoosoo Chang,2,3,4 Seungho Ryu,2,3,4* and Chong Il Sohn1*
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Gastroesophageal reflux disease (GERD), characterized by the presence of symptoms or complications resulting from gastroesophageal reflux, is a chronic relapsing disease that impairs quality of life and is a significant public health challenge in Western nations.1,2 Moreover, the presence of endoscopically confirmed erosive esophagitis (EE) is linked to an elevated risk of Barrett’s esophagus and esophageal adenocarcinoma.3,4 In recent decades, the prevalence of EE has been rapidly increasing globally, as well as in Asian countries, including Korea. Therefore, identifying modifiable risk factors for EE to avoid further increases in its incidence and consequent complications is crucial.
Previous studies have reported a positive correlation between obesity and the occurrence of EE.5-8 The main mechanism by which obesity promotes gastroesophageal reflux and EE is via elevated intra-abdominal pressure with subsequent relaxation of the lower esophageal sphincter.9,10 Other studies have highlighted the significance of body fat distribution patterns, specifically abdominal adiposity, as being more influential than general obesity in increasing the risk of EE.5,11 In addition to the mechanical effects of increased intra-abdominal pressure that occurs in obesity, metabolically active visceral adipose tissue and cytokine-mediated mechanisms may also contribute to the development of EE.5,12 Metabolic disorders such as type 2 diabetes, dyslipidaemia, and metabolic syndrome reportedly affect the development of EE.13,14 These metabolic disorders and obesity frequently coexist but do not always coincide, and the extent of metabolic disturbances can vary among individuals with obesity.15 The variations in metabolic health among individuals with or without obesity, may have different implications regarding the risk of development and remission of EE.
Despite extensive research on EE occurrence, few studies have focused specifically on EE improvement.4,16 Moreover, the effects of obesity and metabolic health status on EE remission have not been explored, and whether metabolic unhealthiness, independent of obesity, influences the occurrence of EE remission remains unclear. Therefore, we aim to compare the EE remission risk among individuals with different phenotypes based on metabolic health and obesity status and investigate the effect of changes in metabolic health over time on the remission of EE in a large sample of Korean adults.
The Kangbuk Samsung Health Study included a cohort of Korean adults aged ≥ 18 years who underwent thorough annual or biennial health check-ups at one of the Kangbuk Samsung Hospital Total Healthcare Center clinics in Seoul and Suwon, Korea, as previously described.17,18 The study population comprised a subset of Kangbuk Samsung Health Study participants who were diagnosed with erosive oesophagitis during screening esophagogastroduodenoscopy (EGD) between January 2011 and December 2017 and underwent at least 1 follow-up endoscopy through December 2019 (n = 18 405). To evaluate the effect of metabolic health status and obesity on EE remission, we applied the following exclusion criteria at baseline (Figure): history of cancer, including gastric cancer; history of gastric surgery; use of gastrointestinal (GI) medication (digestive or antacids); diagnosis of gastroduodenal ulcer; diagnosis of EE; and missing data on body mass index (BMI) or metabolic indices. After excluding 1560 participants who fulfilled one or more of the exclusion criteria, 16 845 individuals were analyzed. To assess the association between changes in metabolic health status and the EE remission risk, we further excluded individuals with no subsequent visits after the first 2 visits, or those identified with EE remission at the second endoscopy. Consequently, 6955 participants were included in the final analysis.
Figure 1. Flow chart of study population.
This study was approved by the Institutional Review Board of Kangbuk Samsung Hospital (IRB No. KBSMC 2019-01-033). This study was conducted using anonymized retrospective data that were collected during routine health screenings; therefore, the need for written informed consent was waived.
Data on demographic factors, health-related behaviours, and medical histories were obtained using a standardized self-administered questionnaire. In addition, anthropometric measurements, blood pressure, and serum biochemical parameters were evaluated by trained medical staff during the health examinations.17,18
Blood samples were collected after a minimum of 10 hours of fasting and included lipid profiles, liver enzymes, high-sensitivity C-reactive protein (hsCRP), fasting blood glucose (FBG), and insulin. The homeostatic model assessment of insulin resistance (HOMA-IR) was performed using the following formula: fasting blood insulin (IU/L) × FBG (mg/dL)/405.
Obesity was defined as a BMI ≥ 25 kg/m2, which is the proposed cutoff value for Asians.19 Abdominal obesity is determined by a waist circumference ≥ 90 cm in men and ≥ 85 cm in women, according to the proposed cutoff values for Koreans.20,21
To be classified as metabolically healthy (MH), individuals were required to have neither insulin resistance (which was defined as having a high HOMA-IR (≥ 2.5)22 nor the following 4 metabolic abnormalities used in the National Cholesterol Education Program and Adult Treatment Panel-III criteria, except waist circumference: elevated FBG levels (≥ 100 mg/dL) or the use of glucose-lowering medications; elevated blood pressure (BP) (≥ 130 mmHg systolic, ≥ 85 mmHg diastolic) or use of antihypertensive drugs; elevated triglyceride levels (≥ 150 mg/dL) or use of a lipid-lowering agent; and reduced high-density lipoprotein cholesterol levels (< 40 mg/dL in men and < 50 mg/dL in women).23 Conversely, being classified as metabolically unhealthy (MU) required the presence of either insulin resistance or at least 1 of the 4 metabolic criteria listed above.
The study participants were categorized into 4 groups according to their obesity and metabolic status as follows: (1) MH nonobese; (2) MU nonobese; (3) MH obese; and (4) MU obese.
The alteration in metabolic health status between the first and second visits was classified into 4 groups: (1) persistent metabolically healthy (MH_MH); (2) metabolically healthy at baseline but progression to metabolically unhealthy at the second visit (MH_MU); (3) metabolically unhealthy at baseline but improvement to metabolically healthy at the second visit (MU_MH); and (4) persistent metabolically unhealthy at both visits (MU_MU).
Experienced endoscopists assessed erosive oesophagitis during EGD screening using an Evis Lucera CV-260 endoscope (Olympus Medical Systems, Tokyo, Japan). EE was diagnosed according to standard criteria based on mucosal breaks or minimal changes, such as erythema and/or whitish discoloration, and was graded using the Los Angeles (LA) classification with Japanese modifications, ranging from grades M to D.24 The analysis focused on the remission of LA-graded A to D EE. EE remission was defined as the presence of EE (LA-graded A to D EE) on endoscopy at the initial visit, followed by its absence on subsequent follow-up examinations.
The baseline characteristics of the participants were classified into 4 groups based on their obesity and metabolic health status. The primary outcome was EE remission (grades A to D). Each participant was followed up from baseline EGD examination until the remission of EE or the last visit, with EGD conducted before the end of 2019. The incidence rates were calculated as the number of incident cases divided by person-years of follow-up. To evaluate the association between the 4 groups and the remission of pre-existing endoscopic EE, Cox proportional hazard models were employed to determine the adjusted hazard ratios with 95% confidence intervals (CIs) for the primary outcome of EE remission compared with the reference exposure groups. The proportional hazard assumptions were assessed using the estimated log survival graphs, and no violations of the assumption were observed.
The model was adjusted for age and sex. A multivariate-adjusted model was constructed, which was further adjusted for confounding factors such as study center (Seoul or Suwon), year of EGD examination, smoking status (never, former, current, or unknown), alcohol consumption (0, < 20, ≥ 20 g/day, or unknown), physical activity (inactive, minimally active, health-enhancing physical activity, or unknown), education level (< 12, ≥ 12 years, or unknown), and total energy intake (quintiles or unknown). To incorporate changes in metabolic health status and obesity, and changes in covariates during the follow-up period, time-dependent analyses were performed, in which metabolic health, obesity category, alcohol consumption, smoking status, physical activity, and total energy intake were treated as time-varying covariates, and baseline sex, center, year of screening, and education level were treated as time-fixed variables. To evaluate the effect of metabolic health status on the subsequent remission of EE, subgroup analyses were performed on nonobese and obese individuals. We also evaluated the interactions based on obesity and compared the likelihood ratio tests between models with and without multiplicative interaction terms.
All analyses were performed using STATA (version 17.0; StataCorp LP, College Station, TX, USA).
At baseline, the average age of the 16 845 participants was 38.6 years (standard deviation, 8.1) and the proportion of male participants was 88.9% (Table 1). The prevalences of MH nonobese, MU nonobese, MH obese, and MU obese were 20.4%, 29.2%, 6.6%, and 43.7%, respectively. The MH group, including the MH nonobese and MH obese groups, tended to be younger with fewer current smokers than the MU group. Compared with the MU nonobese group, the MH obese group exhibited more favorable levels of metabolic components used for the definition of metabolic health, but had higher hsCRP levels.
Table 1 . Baseline Characteristics According to Metabolically Healthy and Obese Status (n = 16 845)
| Characteristics | Overall | Metabolically healthy and obese status | |||
|---|---|---|---|---|---|
| MH nonobese | MU nonobese | MH obese | MU obese | ||
| Number | 16 845 | 3438 | 4925 | 1117 | 7365 |
| Age (yr) | 38.6 (8.1) | 36.1 (7.1) | 40.1 (8.8) | 35.9 (6.9) | 39.2 (7.9) |
| Male | 88.9 | 72.2 | 90.9 | 89.8 | 95.3 |
| Current smoker | 39.0 | 27.1 | 40.6 | 34.3 | 44.2 |
| HEPA | 82.6 | 81.1 | 83.4 | 79.6 | 83.2 |
| High education levela | 86.6 | 88.5 | 85.3 | 90.5 | 86.0 |
| Hypertensionb | 17.6 | 0.0 | 18.8 | 0.0 | 27.8 |
| Diabetesc | 5.8 | 0.0 | 6.3 | 0.1 | 9.0 |
| History of CVD | 1.0 | 0.4 | 1.1 | 0.5 | 1.3 |
| Medication for dyslipidemia | 3.1 | 0.0 | 3.3 | 0.0 | 4.9 |
| Obesityd | 50.4 | 0.0 | 0.0 | 100.0 | 100.0 |
| Abdominal obesity | 41.1 | 4.6 | 9.2 | 59.8 | 76.6 |
| LA classification of erosive esophagitis | |||||
| A | 86.2 | 91.0 | 87.1 | 85.9 | 86.2 |
| B | 13.2 | 8.8 | 12.6 | 13.2 | 13.3 |
| C | 0.5 | 0.2 | 0.4 | 0.9 | 0.5 |
| D | 0.01 | 0 | 0 | 0 | 0.01 |
| Body mass index (kg/m2) | 25.3 (3.4) | 22.1 (1.9) | 23.1 (1.0) | 26.9 (1.8) | 28.1(2.7) |
| Systolic BP (mmHg) | 115.2 (12.1) | 107.1 (9.7) | 114.6 (11.8) | 112.9 (8.5) | 119.7 (11.7) |
| Diastolic BP (mmHg) | 74.0 (9.7) | 67.8 (7.3) | 74.3 (9.7) | 70.5 (6.9) | 77.3 (9.5) |
| Glucose (mg/dL) | 98.6 (17.7) | 90.1 (5.9) | 100.4 (18.6) | 91.3 (5.4) | 102.5 (20.2) |
| Total cholesterol (mg/dL) | 200.4 (35.3) | 189.9 (29.9) | 198.2 (35.7) | 199.6 (32.6) | 207.0 (36.4) |
| LDL-C (mg/dL) | 128.5 (32.8) | 114.8 (28.8) | 126.8 (32.1) | 128.7 (31.0) | 135.9 (32.8) |
| HDL-C (mg/dL) | 53.6 (14.0) | 66.1 (12.7) | 52.6 (13.6) | 60.2 (9.5) | 47.4 (10.9) |
| Triglycerides (mg/dL) | 122 (84-178) | 76 (58-99) | 127 (90-178) | 91 (72-115) | 159 (116-219) |
| ALT (U/L) | 26 (18-40) | 17 (13-25) | 23 (17-33) | 25 (18-36) | 35 (24-52) |
| GGT (U/L) | 34 (21-58) | 20 (14-30) | 31(21-51) | 29 (20-46) | 47 (31-74) |
| hsCRP (mg/L) | 0.6 (0.3-1.2) | 0.3 (0.2-0.7) | 0.5 (0.3-1.0) | 0.6 (0.4-1.1) | 0.9 (0.5-1.7) |
| HOMA-IR | 1.5 (1.0-2.3) | 1.0 (0.6-1.3) | 1.4 (0.9-1.7) | 1.3 (0.9-1.7) | 2.2 (1.5-3.1) |
| Total calorie intake (kcal/day)e | 1602.3 (1246.9-2019.8) | 1513.9 (1149.4-1931.1) | 1592.1 (1246.0-1958.7) | 1579.0 (1200.6-2037.8) | 1666.3 (1297.3-2101.5) |
a≥ College graduate.
bDefined as systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, a history of hypertension, or current use of anti-hypertensive medications.
cDefined as a fasting serum glucose ≥ 126 mg/dL, Hemoglobin A1c ≥ 6.5% a history of diabetes, or current use of anti-diabetic medications.
dBody mass index ≥ 25 kg/m2.
eAmong 11 572 participants with plausible estimated energy intake levels (within 3 standard deviations of the log-transformed mean energy intake).
MH, metabolically healthy; MU, metabolically unhealthy; HEPA, health-enhancing physically active; CVD, cardiovascular disease; LA, Los Angeles; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein-cholesterol; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; hsCRP, high sensitivity C-reactive protein; HOMA-IR, homeostasis model assessment of insulin resistance.
International System of Units (SI) conversion factors: to convert glucose to millimoles per liter, multiply by 0.0555; total cholesterol, HDL-C, and LDL-C to millimoles per liter, multiply by 0.0259; triglycerides to millimoles per liter, multiply by 0.0113; AST, ALT, and GGT to microkatals per liter, multiply by 0.0167; and hsCRP to nanomoles per liter, multiply by 9.524.
Data are expressed as mean (standard deviation), percentage, or median (interquartile range).
During a median follow-up of 2.2 years (interquartile range, 1.8-4.0 years; maximum, 8.8 years), 10 259 cases of EE remission (incidence rate, 242.6 cases per 103 person-years) were identified (Table 2). In a multivariate-adjusted time-dependent model that considered the changing status of BMI categories, metabolic health, and other confounders over time as time-varying covariates, the MH nonobese (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.23-1.37) and MU nonobese (adjusted HR, 1.17; 95% CI, 1.12-1.23) groups demonstrated a significantly higher remission of LA-grade A to D EE than the MU obese group (reference), with the highest remission observed in the MH nonobese group, whereas the MH obese group did not.
Table 2 . Remission of Erosive Esophagitis by Metabolically Healthy Status Among 16 845 Participants With Erosive Esophagitis (Los Angeles Classification A to D) at Baseline
| Metabolically healthy and obese status | PY | Cases of remission | Remission rate (cases per 103 PY) | Age and sex-adjusted HR (95% CI) | Multivariable-adjusted HRa (95% CI) | HR (95% CI)b in model using time-dependent variables |
|---|---|---|---|---|---|---|
| MH nonobese | 7982.7 | 2286 | 286.4 | 1.22 (1.16-1.29) | 1.21 (1.14-1.28) | 1.30 (1.23-1.37) |
| MU nonobese | 12 068.2 | 3139 | 260.1 | 1.14 (1.09-1.20) | 1.14 (1.08-1.19) | 1.17 (1.12-1.23) |
| MH obese | 2953.5 | 595 | 201.5 | 0.92 (0.85-1.01) | 0.93 (0.85-1.01) | 0.98 (0.90-1.06) |
| MU obese | 19 278.0 | 4239 | 219.9 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
aEstimated from Cox proportional hazard models. Multivariable model 1 was adjusted for age, sex, center, year of screening exam, smoking status, alcohol intake, physical activity, educational level and total energy intake.
bEstimated from Cox proportional hazard models with body mass index category, alcohol consumption, smoking status, physical activity, and total energy intake as time-dependent categorical variables and baseline age, sex, center, year of screening exam, education level as time-fixed variables.
PY, person-years; HR, hazard ratio; MH, metabolically healthy; MU, metabolically unhealthy.
Remission of EE (LA grades A to D) was significantly higher in the absence of high BP, high triglycerides, and low high-density lipoprotein cholesterol compared to their presence. This association did not significantly differ by obesity status (Supplementary Table 1). EE remission tended to be higher in nonobese participants in the absence of high glucose, but this was not statistically significant in overall, obese, and nonobese groups. The number of LA-C and LA-D EE cases were 86 and 1, respectively. Among LA-B EE cases at baseline (n = 2243), the association between metabolic components and EE remission was similar for high BP, with none of the metabolic components significantly associated with EE remission, and no significant interaction by obesity (Supplementary Table 2).
In sensitivity analyses, we adjusted for GI medication use during the follow-up period and performed a sensitivity analysis after excluding the 241 participants who took GI medication during follow-up. These analyses yielded results similar to the original findings. We have included this information in Supplementary Tables 3 and 4.
When the metabolic health and non-obesity were separately evaluated in EE remission, both were significantly associated with EE remission (Supplementary Table 5).
Table 3 presents the remission of EE according to the changing status of metabolic health between the first and second visits. Compared with the persistent MU group (MU_MU) as a reference, the persistent MH group (MH_MH; adjusted HR, 1.37; 95% CI, 1.23-1.52) and both the improvement and worsening groups of metabolic health status (MU _MH and MH_MU; adjusted HR, 1.28; 95% CI, 1.12-1.46 and adjusted HR, 1.15; 95% CI, 1.01-1.30, respectively) showed higher EE remission, with the highest remission rate observed in the persistent MH group, in the time-dependent model (Table 3).
Table 3 . Remission of Erosive Esophagitis by Changes of Metabolically Healthy Status Among 6955 Participants With Erosive Esophagitis (Los Angeles Classfication A to D) at Baseline
| Changes of metabolically healthy status | PY | Cases of remission | Remission rate (cases per 103 PY) | Age and sex-adjusted HR (95% CI) | Multivariable-adjusted HRa (95% CI) | HR (95% CI)b in model using time-dependent variables |
|---|---|---|---|---|---|---|
| MH_MH | 6469.2 | 1915 | 296.0 | 1.23 (1.11-1.36) | 1.23 (1.11-1.37) | 1.37 (1.23-1.52) |
| MH_MU | 4466.9 | 966 | 216.3 | 0.98 (0.87-1.11) | 0.98 (0.87-1.11) | 1.15 (1.01-1.30) |
| MU_MH | 3498.7 | 963 | 275.2 | 1.09 (0.96-1.24) | 1.08 (0.94-1.23) | 1.28 (1.12-1.46) |
| MU_MU | 27 847.5 | 6415 | 230.4 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
aEstimated from Cox proportional hazard models. Multivariable model 1 was adjusted for age, sex, center, year of screening exam, smoking status, alcohol intake, physical activity, educational level and total energy intake.
bEstimated from Cox proportional hazard models with body mass index category, alcohol consumption, smoking status, physical activity, and total energy intake as time-dependent categorical variables and baseline age, sex, center, year of screening exam, education level as time-fixed variables.
PY, person-years; HR, hazard ratio; MH, metabolically healthy; MU, metabolically unhealthy; MH_MH, persistent metabolically healthy; MH_MU, metabolically healthy at baseline but progression to metabolically unhealthy at the second visit; MU_MH, metabolically unhealthy at baseline but improvement to metabolically healthy at the second visit; MU_MU, persistent metabolically unhealthy at both visits.
The association between metabolic health changes and EE remission did not differ significantly by obesity or abdominal obesity status (Table 4). Increased EE remission in the persistent MH group was consistently observed in the individuals without either general or abdominal obesity.
Table 4 . Remission of Erosive Esophagitis by Changes of Metabolically Healthy Status According to Obesity Among Participants With Erosive Esophagitis (Los Angeles Classification A to D) at Baseline
| Changes of metabolically healthy status | Multivariable-adjusted HRa (95% CI) | P for interaction by obesity | ||
|---|---|---|---|---|
| Obesity based on BMI (n = 6955) | Nonobese BMI < 25 kg/m2 (n = 3230) | Obese BMI ≥ 25 kg/m2 (n = 3725) | ||
| MH_MH | 1.29 (1.14-1.46) | 0.96 (0.76-1.20) | 0.078 | |
| MH_MU | 0.99 (0.84-1.16) | 0.96 (0.78-1.17) | ||
| MU_MH | 1.17 (0.98-1.39) | 0.94 (0.76-1.16) | ||
| MU_MU | 1.00 (reference) | 1.00 (reference) | ||
| Abdominal obesity based on waist circumference (n = 6099) | Abdominal nonobese (n = 3419) | Abdominal obese (n = 2680) | ||
|---|---|---|---|---|
| MH_MH | 1.22 (1.07-1.39) | 1.02 (0.78-1.33) | 0.630 | |
| MH_MU | 0.99 (0.84-1.16) | 0.91 (0.72-1.16) | ||
| MU_MH | 1.03 (0.86-1.23) | 1.04 (0.81-1.34) | ||
| MU_MU | 1.00 (reference) | 1.00 (reference) | ||
aEstimated from Cox proportional hazard models. Multivariable model 1 was adjusted for age, sex, center, year of screening exam, smoking status, alcohol intake, physical activity, educational level and total energy intake.
BMI, body mass index; MH, metabolically healthy; MU, metabolically unhealthy; MH_MH, persistent metabolically healthy; MH_MU, metabolically healthy at baseline but progression to metabolically unhealthy at the second visit; MU_MH, metabolically unhealthy at baseline but improvement to metabolically healthy at the second visit; MU_MU, persistent metabolically unhealthy at both visits.
In this large-scale cohort study of young and middle-aged Korean adults, we examined the EE remission according to different phenotypes based on metabolic health and obesity status. Compared with the MU obese group, the nonobese (MH nonobese and MU nonobese) groups exhibited a significantly higher rate of EE remission with the highest EE remission observed in the MH nonobese group. We also investigated the association between changes in the metabolic health status and EE remission. Both the persistent MH and improvement groups (MU to MH) demonstrated a significantly increased rate of EE remission compared with the persistent MU group, with the highest EE remission observed in the persistent MH group. Therefore, maintaining and improving metabolic health may contribute to the remission of EE. Additionally, an increased rate of EE remission was consistently observed in the persistent MH group, even in individuals without obesity (or abdominal obesity). Our results indicated that metabolic health, even in the absence of obesity, may play a crucial role as an independent factor in EE remission.
Most previous studies have primarily focused on identifying the factors that lead to EE. Currently, research focusing specifically on the remission of EE is limited.4,16,25 Few studies have been conducted regarding the association between decreased BMI and improvement in GERD symptoms or remission of EE.4,25 A retrospective longitudinal study involving 15 295 health check-up participants with GERD symptoms reported that weight loss (≥ 2 kg/m2 decrease in BMI; adjusted HR, 2.34; 95% CI, 1.70-2.83) or decreased waist circumference (≥ 5 cm decrease in waist circumference; adjusted HR, 2.16; 95% CI, 1.56-2.90) significantly improved GERD symptoms in individuals with general or abdominal obesity.25 Another retrospective longitudinal study of 1126 individuals with EE demonstrated that a reduction in BMI (adjusted HR [95% CI] for BMI reduction of ≤ 1, 1-2, and ≥ 2 kg/m2; 1.09 [0.89-1.35], 1.31 [1.10-1.72], and 2.12 [1.44-3.12], respectively) was significantly associated with the remission of EE in a dose-response relationship.4 The traditional view links general (elevated BMI) and abdominal obesity (increased waist circumference) to EE through acid reflux caused by increased gastroesophageal sphincter gradient arising from increased intra-abdominal pressure and prolonged transient lower esophageal sphincter relaxation.9,10,26 However, given that not all obese individuals have EE, the pathogenesis must be multifactorial and cannot be solely attributed to a single physiological parameter.27,28 Recently, new perspectives suggest that metabolic and inflammatory pathways may play a role.9,29 Visceral adipose tissue overproduces pro-inflammatory cytokines which can lead to esophageal circular muscle relaxation and gastrin secretion;26,30,31 various adipocytokines derived from the visceral adipose tissue further contribute to systemic inflammation, creating a vicious cycle that aggravates each mechanism.26,29 These processes, combined with pathological acid exposure, can cause chronic inflammation at the esophagogastric junction, ultimately leading to the development and exacerbation of EE.14,26,29 Recently, one prospective cohort study involving 163 patients with EE assessed the longitudinal impact of abdominal visceral fat volume and its changes, measured using cross-sectional computed tomography, on the remission of EE.16 In this study, a higher visceral fat volume at follow-up and a greater increase in this volume during the follow-up period were significantly linked to decreased remission of EE in a dose-dependent manner, suggesting that reducing visceral fat may promote the remission of EE.16 Another longitudinal study from Taiwan including 603 participants with EE at baseline revealed that having metabolic syndrome independently attenuated the likelihood of EE remission (relative risk, 0.74; 95% CI, 0.53-0.98).28 Nonetheless, these studies did not distinguish between the impacts of obesity and metabolic abnormalities, both of which likely contribute to the remission of EE. Growing evidence indicates that obesity can be divided into specific phenotypes depending on the presence or absence of metabolic disorders, such as hypertension, diabetes, and dyslipidaemia.32-34 These phenotypes bear clinical significance, and individuals with varying obesity and metabolic health statuses likely face different likelihoods of EE remission. In the present study, metabolic health and nonobesity were identified as independent and significant contributing factors to EE remission after adjustment for other potential confounders. Additionally, even among nonobese (and nonabdominally obese) individuals, maintaining or enhancing metabolic health independently and favourably affected EE remission. Although obesity and metabolic abnormalities are closely related and could have confounded the outcomes, our findings suggest that separate or combined phenotypes of sustained nonobesity and metabolic health appear to contribute independently to EE remission. Further studies are required to assess the importance of ameliorating insulin resistance and promoting metabolic health on EE remission.
To our knowledge, this is the first longitudinal cohort study to compare the risk of EE remission among MH nonobese, MU nonobese, MH obese, and MU obese groups. Importantly, this large-scale investigation incorporated high-quality, standardized clinical and laboratory parameters, along with a detailed phenotype based on repeated assessments of obesity and metabolic health status according to a strict definition. Furthermore, this is the first study to distinguish between the influences of metabolic health status and obesity and to establish an association between metabolic health, temporal changes, and remission of EE.
Nevertheless, this study has several limitations. First, the lack of information regarding co-medications, such as proton pump inhibitors and histamine-2 receptor antagonists, which could potentially have a therapeutic effect on EE, made it impossible to exclude the possibility that participants whose EE was resolved with the use of these medications were included in the study.14,35 Second, the study did not assess interobserver variations in endoscopic diagnoses of EE. However, all endoscopic examinations and procedures were conducted by experienced board-certified gastroenterologists who applied the same classification system with a well-defined definition of EE for all participants. Finally, because the study’s results were mainly derived from a sample of young, middle-aged, and relatively healthy Koreans, the generalizability of the findings to older age groups or individuals of different races may be limited. Despite these limitations, our data contribute significantly to enhance the understanding of the distinct role of metabolic health on the rate of EE remission.
In conclusion, metabolic health independently contributes to EE remission, irrespective of obesity status. Considering the association between metabolic health and EE remission, individuals with EE should assess their metabolic health status and strive to achieve a healthy metabolic state.
None.
None.
Seungho Ryu and Chong Il Sohn designed and directed the study, including quality assurance and control; Seungho Ryu analysed the data and designed the analytical strategy for the study; Seungho Ryu and Chong Il Sohn supervised field activities; and Nam Hee Kim and Yoosoo Chang drafted the manuscript. All the authors interpreted data and conducted a literature review and prepared the Materials, Methods, and Discussion sections. All authors contributed to the critical revision of the manuscript.
Note: To access the supplementary tables mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm24058.
Author ORCID Information
Nam Hee Kim Yoosoo Chang Seungho Ryu Chong Il Sohn |
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