Increased Triglyceride‑Glucose Index as a Predictive Biomarker for Gastroesophageal Reflux Disease and Erosive Reflux Disease

• The prevalence of GERD has influenced by multiple factors including obesity, dietary habits, and sedentary lifestyles                                    
• Recent interest has emerged in the metabolic underpinnings of GERD, particularly the role of insulin resistance (IR).                                     
• The triglyceride-glucose (TyG) index, derived from fasting plasma triglyceride and glucose concentrations, is plausible it may correlate with GERD risk or severity

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a prevalent esophageal motility disorder characterized by the retrograde movement of gastric contents into the esophagus, resulting in clinical manifestations such as pyrosis and, in some cases, regurgitation.", and esophageal mucosal injury [1]. The prevalence of GERD has been rising globally, influenced by multiple factors including obesity, dietary habits, and sedentary lifestyles [2]. Recent interest has emerged in the metabolic underpinnings of GERD, particularly the role of insulin resistance (IR), which may contribute to the pathophysiology of GERD through mechanisms involving delayed gastric emptying, increased abdominal pressure, and esophageal dysmotility [3].

The triglyceride-glucose (TyG) index, derived from fasting plasma triglyceride and glucose concentrations, is widely recognized as a practical and dependable surrogate indicator of insulin resistance [3]. Compared to more invasive methods like the hyperinsulinemic-euglycemic clamp or the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose (TyG) index offers a more practical and economical alternative for assessing insulin resistance, and its diagnostic performance has been validated in various populations [4]. Given the strong association between insulin resistance and obesity-related comorbidities, it is plausible that the TyG index may correlate with GERD risk or severity.                                                    

Recent studies have begun to explore the link between metabolic indices, including TyG, and gastrointestinal disorders [5]. However, the evidence regarding a direct relationship between the TyG index and GERD remains limited and inconclusive, necessitating further clinical investigation.                                            

Understanding the relation between GERD and the TyG index could offer novel insights into the metabolic contributors to GERD and may help identify high-risk individuals through a simple biochemical marker.

PATIENTS AND METHODS

This cross-sectional study was conducted on 70 patients having gastroesophageal disease and normal controlled patients of the same age and sex came to endoscopy unit complaining of gastroesophageal symptoms but negative to GERD.

The participants selected from records of outpatients and inpatients of tropical medicine department (Menoufia University hospital) in the period from January 2024 to March 2025 and they classified into two groups; GI: Include patients with GERD. GII: Include normal controlled patients of the same age and sex. Exclusion criteria were that patients receiving ongoing anti-diabetic therapy, fasting plasma glucose ≥ 126mg/dl, Individuals with antecedent cancer or gastrectomy, current use of lipid-lowering drugs targeting triglycerides, or severe hypertriglyceridemia (TG>400mg/dl).

Comprehensive history-taking was conducted, emphasizing the presence of dyspeptic manifestations (e.g., epigastric pain, nausea, vomiting, heartburn, regurgitation, gastrointestinal bleeding), along with assessment of smoking habits, alcohol use, and relevant medical history including hypertension. Clinical examination was done including general and abdominal. Anthropometric measurements, including height, body weight, and waist circumference, were recorded. Body mass index (BMI) was calculated as body weight divided by height squared (kg/m2).

Laboratory investigations: included fasting glucose, total cholesterol, TG, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol levels, and h.pylori stool antigen.   The TyG index was calculated using the formula: [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)] / 2.

Upper endoscopic evaluation was done. The diagnosis of GERD was established using endoscopic evaluation, with reflux esophagitis classified according to the Los Angeles (LA) grading system (grades A–D). Erosive reflux disease (ERD) was defined as the presence of LA grade B or higher [6]. There was no time lag between endoscopic evaluation and laboratory investigations.

RESULTS

Statistical analysis

Data collection, organization, and analysis were performed using  Personal computer conforming to IBM standards with Version 26 of the Statistical Package for the Social Sciences(SPSS) (IBM Corp., Armonk, NY: IBM Corp). Statistical analysis performed were descriptive statistics e.g. qualitative data were expressed as Number (N), percentage (%), while quantitative data were expressed as mean (x̅), standard deviation (SD) and analytic statistics e.g.  Student’s t-test (t) is a test of significance used for comparison of quantitative variables between two groups of normally distributed data, while for qualitative variables chi- square, (ANOVA) used for the differentiation of three classes of variants according to the mean. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under curve (AUC), were calculated by using the receiver operating characteristic curve (ROC) which is a graphic representation of the relationship between them at different cutoff points for a diagnostic test.

Statistically significant increase in the weight, BMI, waist, obesity cases, smoking cases and H pylori infected patients in GERD group than controls, while no significant statistical difference between the study groups regarding age, gender, height, measured blood pressure parameters, including systolic and diastolic values and hypertensive cases. Table 1                                               

Laboratory findings showed significant increase in FBS, total cholesterol, TG, and LDL in GERD patients, also TyG index was markedly higher among GERD patients compared with the control group. The mean value in the GERD cohort reached 10.78 ± 2.75, while controls demonstrated a substantially lower mean of 4.495 ± 1.112. (Table 2, Fig 1). Upper endoscopy showed that there were 29 patients with GERD grade A (41.43%), 23 patients GERD grade B (32.86%), 16 patients GERD grade C (22.86%) and 2 patients GERD D (2.86%). Table 2                                   

 Univariate regression analysis demonstrated that the triglyceride-glucose (TyG) index was significantly associated with several risk factors for GERD. Current smoking, hypertension, and obesity showed positive correlations with higher TyG values (P = 0.045, 0.005, and 0.001, respectively). In addition, patients with erosive reflux disease (ERD) had significantly elevated TyG indices compared with those without ERD (P = 0.007). According to the Los Angeles classification, the TyG index tended to increase with disease severity, particularly in grade C, and ANOVA confirmed the overall significance across grades (P = 0.016). On the other hand, sex, H. pylori infection, and grade B did not demonstrate a significant effect on TyG index levels in the univariate model. Table 3

In the multivariate analysis, obesity was strongly associated with GERD, showing an odds ratio of 98.7 with a wide confidence interval (4.9–1991.5) and a highly significant P value (0.003). Similarly, H. pylori infection increased the risk by almost 23.6 times (95% CI: 2.1–264.5, P = 0.010). The TYG index demonstrated a protective effect, with an odds ratio of 0.625 (95% CI: 0.447–0.873, P = 0.006). In contrast, current smoking showed no significant independent association (OR = 0.20, 95% CI: 0.008–4.71, P = 0.318). Table4

The validity of TYG index in prediction of GERD by ROC curve at cut off level>7.5 with sensitivity 94.29, specificity 90, PPV 95.3, NPV100 and accuracy 92.3%. The validity of TYG index in prediction of ERD by ROC curve was at cut off level >9.4 with sensitivity 85.37, specificity 65.52, PPV 77.8, NPV 76 and accuracy 71%. Table 5, Figure 2, 3                                                           

Table 1: Base line and demographic and clinical characteristics of the study groups

Table 2: Laboratory and endoscopic findings between the studied groups

Data was presented as mean± SD or range or frequency (%). FBS: Fasting blood sugar, TG: triglyceride    HDL: high density lipoproteins LDL: Low density lipoprotein, TYG index: Triglyceride glucose index, LA: Los Anglos classification. *: significant as P value ≤ 0.05. GERD: gastroesophageal reflux disease.

Table3: Univariate analysis of risk factors for GERD

Data was presented as mean± SD or range or frequency (%). FBS: Fasting blood pressure, TG: triglyceride    HDL: high density lipoproteins LDL: Low density lipoprotein, TYG index: Triglyceride glucose index, LA: Los Anglos classification. *: significant as P value ≤ 0.05. GERD: gastroesophageal reflux disease.
Table 4: Multivariate analysis of risk factors for GERD

Data was presented as CI: confidence interval. *: significant as P value ≤ 0.05. GERD: gastroesophageal reflux disease, TYG: triglyceride-glucose index.

Table 5: ROC curve between GERD group, control group, ERD and no ERD

Data was presented as frequency (%). PPV: Positive predictive value, NPV: Negative predictive value, GERD: gastroesophageal reflux disease, TYG Index: triglyceride-glucose.

DISCUSSION

In the present study, both body weight and body mass index showed statistically significant elevation, waist circumference, obesity prevalence, smoking frequency, and H. pylori among GERD patients compared with the controls was observed. The current results reinforce the notion that lifestyle and metabolic factors are key contributors to GERD pathogenesis. Adiposity, in particular, is strongly linked to increased intra-abdominal pressure, which promotes the retrograde movement of gastric contents into the esophagus [7]. Similar associations were reported by El-Serag et al., [8] who noted a higher incidence of GERD among individuals with central obesity and a higher BMI, suggesting mechanical and hormonal influences in GERD development .          

Importantly, no statistically significant differences were detected between GERD and control groups regarding age, gender, height, systolic and diastolic blood pressure, or hypertension prevalence. This agreed with Li et al. [9] demonstrated that metabolic disturbances particularly abdominal obesity, dyslipidemia, insulin resistance, and impaired glucose metabolism are stronger predictors of GERD than demographic factors like age or gender. This contrasts with earlier studies that reported higher GERD prevalence in older adults and females [10]. Our findings suggest that metabolic disturbances, rather than demographic parameters, may better predict GERD risk in certain populations.                                 

In terms of laboratory findings, GERD patients exhibited significantly elevated fasting blood sugar (FBS), triglycerides (TG), total cholesterol, and circulating levels of low-density lipoprotein (LDL), supporting the concept that GERD may be part of a broader metabolic dysfunction spectrum. The current data corroborate the results of Park et al., [11] who documented increased levels of metabolic parameters, including dyslipidemia and hyperglycemia, in GERD patients, especially those with erosive forms.                                                                                                                                      

In the univariate analysis, the TyG index, a validated surrogate marker for insulin resistance levels were significantly elevated in patients with GERD relative to the control group. This supports the hypothesis that insulin resistance may be mechanistically linked to GERD. Insulin resistance can affect esophageal motility, delay gastric emptying, and weaken lower esophageal sphincter (LES) tone, thereby facilitating reflux [4]. Han et al. [12] recently confirmed the link between a high triglyceride-glucose (TyG) index and the increased likelihood of developing GERD and ERD in a large cross-sectional cohort, highlighting TyG as a non-invasive predictor of esophageal mucosal damage. 

  In the multivariate analysis, obesity emerged as powerful independent predictor of GERD, with an odds ratio of 98.7 (95% CI: 4.9–1991.5, P = 0.003). This result agrees with previous meta-analyses that highlighted the central role of adiposity in reflux pathogenesis [7]. Likewise, H. pylori infection was found to increase GERD risk more than 23-fold (95% CI: 2.1–264.5, P = 0.010), consistent with some studies linking infection or eradication to reflux [13], although others reported a protective effect in certain populations [14]. Interestingly, the TyG index demonstrated an inverse association (OR = 0.625, 95% CI: 0.447–0.873, P = 0.006), which contradicts larger cohorts that described a positive relationship between higher TyG and GERD risk [15, 9].  This discrepancy may be explained by collinearity with obesity in our relatively small sample. The inverse association of TyG index in the multivariate analysis likely reflects collinearity with obesity, as both variables capture overlapping aspects of metabolic risk. When obesity was excluded from the model, TyG maintained a positive association with GERD, consistent with univariate and ROC finding.  Current smoking did not show an independent effect (OR = 0.20, P = 0.318), a result likely related to the limited number of smokers, since previous reports have consistently shown smoking to impair lower esophageal sphincter function and increase reflux episodes [16].  

Endoscopic evaluation in our study classified GERD patients into Los Angeles (LA) grades A through D, with the majority being grade A (41.43%) and grade B (32.86%). A notable finding was that the TyG index increased progressively with the severity of erosive reflux, especially in patients who were obese, hypertensive, or smokers. This observation aligns with the study by Wang et al., [17], who showed a significant elevation in TyG index values in patients with erosive esophagitis compared to NERD and control groups. These findings underscore the role of metabolic stress and lifestyle-related inflammation in mucosal injury.                                                                                 

Interestingly, no statistically significant difference in TyG index values was found in GERD patients with H. pylori infection. Existing evidence indicates that metabolic disturbances, as indicated by the TyG index and related parameters, likely overshadow the influence of Helicobacter pylori infection in the pathogenesis of GERD. When insulin resistance and dysmetabolism are prominent, any acid modulating effect of H. pylori become less clinically relevant, resulting in GERD cases, TyG levels did not differ significantly between those infected with H. pylori and those who were not [18], this contradicts some earlier studies that proposed H. pylori as a protective factor against ERD by reducing gastric acid secretion in chronic infection stages [19]. However, our data suggest that when metabolic risk factors are present, the influence of H. pylori on GERD may be less pronounced or non-contributory.                           

In our study, the TyG index demonstrated excellent predictive capability for GERD, with a threshold value above 7.5 yielding a sensitivity of 94.29%, specificity of 90%, and overall diagnostic accuracy of 92.3%. These findings suggest the TyG index may function as a reliable and practical non-invasive screening tool, particularly in settings with limited access to endoscopic evaluation. Our results are in line with prior research by Simental-Mendía et al., [3] who established that the triglyceride-glucose index offered a consistent and accessible measure of insulin resistance in clinical and epidemiological contexts. Additional support comes from a large Korean cohort study by Kim et al., [15], which observed a stepwise increase in the risk of both GERD and erosive reflux disease (ERD) across TyG index quartiles, with the highest quartile associated with more than a fourfold increase in GERD risk and over sevenfold increase in ERD risk compared to the lowest quartile.

On the other hand, some studies have reported more modest predictive value of the TyG index in GERD. A population-based investigation involving over 120,000 Taiwanese individuals found a statistically significant association between TyG index and GERD; however, the strength of this association was relatively weak, with other obesity-related measures such as waist-to-hip ratio and visceral adiposity showing stronger correlations [12]. Furthermore, in pediatric and lower-risk populations, the TyG index has shown only moderate diagnostic utility. For example, a study conducted in Argentine school-aged children reported limited sensitivity and specificity, with area under the ROC curve estimates around 0.70 [20]. These observations suggest that although the TyG index holds promise as a GERD biomarker, especially in metabolically at-risk adults, its diagnostic performance may vary based on population characteristics and clinical context.

For ERD prediction, the TyG index had a cut-off value of >9.4 with sensitivity of 85.37% and specificity of 65.52%, indicating lower specificity but still reasonable diagnostic power. This finding suggests that while TyG can help stratify patients with higher mucosal damage, it may need to be combined with other markers or clinical indicators for precise risk stratification.

A limitation of the present study is that the TyG index was not reassessed after correction of obesity, dyslipidemia, or hyperglycemia. As a result, it remains unclear whether improvements in these metabolic parameters would alter the observed association between TyG and GERD. In addition, the relatively small sample size may have contributed to the wide confidence intervals observed in the multivariate model, particularly for obesity. Despite these limitations, our study has strengths, including the use of both univariate and multivariate analyses, as well as ROC curve evaluation, which together provide a more comprehensive assessment of the relationship between metabolic indices and GERD.

CONCLUSION

The present study adds to the Growing body of research that supports a strong link between metabolic dysregulation especially insulin resistance and GERD, particularly ERD. The TyG index shows promise as a non-invasive, cost-effective tool for early identification of at-risk patients. Future longitudinal studies are needed to explore whether TyG reduction through metabolic interventions could reduce GERD severity or progression.

List of abbreviations

GERD: gastroesophageal reflux disease, IR: insulin resistance, TyG: triglyceride-glucose, BMI: body mass index, HDL: high-density lipoprotein, ERD: erosive reflux disease, IQR: interquartile range, FBS: fasting blood sugar, LDL: low-density lipoprotein, LES: lower esophageal sphincter.                                                   

Ethical approval:

Written informed consent was obtained from all participants prior to their enrollment in the study, in accordance with institutional and ethical guidelines. The study was approved by the institutional review board with an approval number (10/2024 TROP 7).                

Author contribution:

Conceptualization: H.M.E & W.A.S, methodology: H.M.E, W.A.S Formal analysis and investigation: W.A.S Writing—original draft preparation: H.M.E, writing—review and editing: W.A.S, H.M.E, supervision, validation and final editing: H.M.E, all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding: No funds

Conflict of interest: None