leptin and Gastroesophageal-Reflux

Central obesity is involved in the pathogenesis and progression of Barrett's esophagus to esophageal adenocarcinoma. Involved are likely both mechanical and nonmechanical effects. Mechanical effects of increased abdominal fat cause disruption of the gastroesophageal reflux barrier leading to increased reflux events. Nonmechanical effects may be mediated by inflammation, via classically activated macrophages, pro-inflammatory cytokines, and adipokines such as Leptin, all of which likely potentiate reflux-mediated inflammation. Insulin resistance, associated with central obesity, is also associated with both Barrett's pathogenesis and progression to adenocarcinoma. Molecular pathways activated in obesity, inflammation and insulin resistance overlap with those involved in Barrett's pathogenesis and progression.

Topics: Adiponectin; Barrett Esophagus; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Obesity, Abdominal

Obesity is an important public health problem worldwide. It increases the risk of many chronic diseases such as diabetes and cardiovascular diseases. Meanwhile, obesity is a major risk factor for several types of cancer including gastric cancer. Possible mechanisms linking obesity with gastric cancer may include obesity associated gastro-oesophageal reflux, insulin resistance, altered levels of adiponectin, leptin, ghrelin, and an abnormally increased blood level of insulin-like growth factor (IGF). Helicobacter pylori (H. pylori) infection is a well-recognized risk factor for peptic ulcer and gastric cancer. Recent studies have revealed an increased prevalence of H. pylori infection in obese patients, providing another clue for the increased incidence of gastric cancer in obese population. If this connection can be confirmed in animal models and a large cohort of patients, then eradicating H. pylori together with life style modification in obese individuals may help prevent the development of gastric cancer in the increasingly obese population.

Topics: Adiponectin; Animals; Gastroenteritis; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Obesity; Risk Factors; Signal Transduction; Stomach Neoplasms

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain

To review the concept of a possible link between asthma and obstructive sleep apnea syndrome (OSAS) and the impact on asthma symptoms of treatment of OSAS with continuous positive airway pressure (CPAP) in patients with both conditions.. The Ovid, MEDLINE, and PubMed databases from 1950 to the present were searched for relevant articles regarding a possible relationship between asthma and OSAS and the effectiveness of CPAP in treating OSAS.. Articles describing pathophysiologic conditions occurring in OSAS that may be linked to asthma pathogenesis were used for this review.. The data suggest that OSAS is an independent risk factor for asthma exacerbations. CPAP has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Ameliorative mechanisms of treatment with CPAP include mechanical and neuromechanical effects, gastroesophageal acid reflux suppression, local and systemic anti-inflammatory effects (including suppression of increased serum levels of inflammatory cytokines, chemokines, and vascular endothelial growth factor), cardiac function improvements, leptin level suppression, weight reduction, and sleep restoration.. Asthma and OSAS are increasingly troublesome public health issues. Mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics. We describe potential mechanisms whereby CPAP, the first line of therapy for OSAS, might modify airway smooth muscle function and asthma control in patients with both disorders. Despite the ever-increasing population of patients with both disorders, large, prospective, randomized controlled studies are necessary to more fully evaluate CPAP and asthma outcomes.

Topics: Asthma; Continuous Positive Airway Pressure; Gastroesophageal Reflux; Heart; Humans; Inflammation; Leptin; Obesity; Respiratory Mechanics; Risk Factors; Sleep; Sleep Apnea, Obstructive

The main aim of the study was to assess the relationship between leptin, ghrelin, insulin-like growth factor 1 (IGF-1), and glucagon-like peptide 1 (GLP-1) blood levels and gastric motility in children with obesity compared to healthy children. Secondary aims were to assess the possible association between these hormones and obesity, reflux impedance parameters, reflux symptoms, other GI disorders, and quality-of-life scores within the same groups.. Children with obesity plus GERD symptoms and 2 control groups of children with obesity without GERD and healthy lean children aged 4-17 years underwent an auxological evaluation, an assessment of gastro-intestinal symptoms and quality of life, hormonal dosages, and an evaluation of gastric emptying time (GET) through 13C-octanoic acid breath test.. No significant association was found between hormones and gastric motility. Leptin and ghrelin levels were significantly associated with obesity parameters. No significant differences were found between GET and hormones of the patients with obesity, either with or without GERD.. Although we found an association between auxological parameters and both leptin and ghrelin levels, this association did not imply an effect on the upper GI motility. Therefore, our hypothesis that alterations of these hormones in children with obesity could affect gastric emptying, triggering GERD, was not supported by our data.

Topics: Child; Correlation of Data; Esophageal pH Monitoring; Female; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Diseases; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Quality of Life

Abdominal obesity is a risk factor for Barrett's esophagus independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenic pathway of esophageal adenocarcinoma.. To evaluate whether ghrelin and leptin may partially explain the association between obesity and Barrett's esophagus.. We conducted a case-control study using patients with a new diagnosis of Barrett's esophagus (cases) and two control groups frequency matched to cases for age, gender, and geographic region: (1) patients with gastroesophageal reflux disease (GERD) and (2) a sample of the general population. We generated odds ratios using logistic regressions to evaluate quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for Barrett's esophagus. We evaluated potential interaction variables using cross products and ran stratified analyses to generate stratum-specific odds ratios.. A total of 886 participants were included in the analysis. Higher ghrelin concentrations were associated with an increased risk of Barrett's esophagus, when compared to the population controls, but not the GERD controls. Ghrelin concentrations were not associated with the frequency of GERD symptoms, but ghrelin's relationship with Barrett's esophagus varied significantly with the frequency of GERD symptoms. Leptin concentrations were positively associated with at least weekly GERD symptoms among the population controls and were inversely associated with Barrett's esophagus only among the GERD controls. Adjusting for waist circumference did not change the main associations.. Higher levels of ghrelin were associated with an increased risk of Barrett's esophagus among the general population. In contrast, leptin was positively associated with frequent GERD symptoms, but inversely associated with the risk of Barrett's esophagus among the GERD controls.

Topics: Adult; Aged; Barrett Esophagus; Biomarkers; California; Case-Control Studies; Female; Gastroesophageal Reflux; Ghrelin; Humans; Leptin; Logistic Models; Male; Middle Aged; Obesity, Abdominal; Odds Ratio; Risk Factors; Time Factors; Young Adult

To reveal the specific features of gastroesophageal reflux disease (GERD) associated with obesity and overweight, by investigating the clinical and endoscopic manifestations of the disease, 24-hour pH-metry scores, and leptin levels.. A total of 131 patients with GERD were examined. The data about complaints and those from life and medical histories were collected; anthropometric measurements and the results of blood biochemical tests, esophagoduodenoscopy (EPDS), and pH-metry were assessed; and the serum levels of leptin and its receptor were estimated. The patients were allocated into a study group (104 obese and/or overweight patients) and a comparison one (27 normal weight people).. Waist circumference, hip circumference, and blood glucose levels proved to be statistically significantly higher in the study group (p<0.00000, p<0.00002, and p<0.02, respectively). The obese patients were found to have a statistically significantly higher level of leptin and a lower level of its soluble receptors: the median leptin levels were 30.42 (13.42-45.62) ng/ml in the study group and 5.47 (3.35-7.68) ng/ml in the comparison group; the median levels of the receptors were 18.83 (14.98-25.11) ng/ml and 30.93 (24.68-33.53) ng/ml, respectively). This group showed a moderate negative correlation between these indicators (rs=-0.451; p<0.0004). The study group displayed higher pH values in the gastric cardia and body (p<0.05 and p<0.04, respectively). The mucosal contact time with the refluxate having with a low pH value (<4) in the above segments turned out to be longer in the comparison group (p<0.05). There were weight-independent relationships of the leptin level to its spread, aggressiveness quotient, to the highest pH value in the gastric cardia and body, and to the mucosal contact time with the refluxate having a pH below 4.0 (rs=0.543; p<0.006; rs=0.432; p<0.04; rs=0.431; p<0.04; rs=-0.450; p<0.03, respectively), leptin receptors with a pH ratio in the gastric cardia and body, to the number of reflux episodes longer than 5 minutes in the esophagus, and to the De Meester index for this indicator (rs=0.471; p<0.04; rs=-0.455; p<0.04; rs=-0,454; p<0.04, respectively).. Obese and overweight patients develop GERD in the presence of leptin resistance and biliary tract disease, which determines the specific features of the disease (alkaline or mixed refluxate) and the need for individualized therapy.. Цель исследования. Выявление особенностей течения гастроэзофагеальной рефлюксной болезни (ГЭРБ), ассоциированной с ожирением и избыточной массой тела, на основании изучения клинических и эндоскопических проявлений заболевания, данных суточной рН-метрии и продукции лептина. Материалы и методы. Обследовали 131 больного ГЭРБ. Выполняли сбор жалоб, анамнеза жизни и заболевания, оценку антропометрических показателей, биохимического анализа крови, результатов эзофагодуоденоскопии (ЭФГДС), рН-метрии, уровней лептина и его рецептора в сыворотке крови. Пациентов распределили в основную группу (104 больных с ожирением и/или избытком массы тела) и группу сравнения (27 с нормальной массой тела). Результаты. Окружность талии, бедер, уровень глюкозы в крови оказались статистически значимо выше в основной группе (p<0,00000; p<0,00002 и p<0,02 соответственно). У пациентов с ожирением выявлены статистически значимо более высокий уровень лептина и более низкий уровень растворимых рецепторов к нему: медиана уровня лептина 30,42 (13,42; 45,62) нг/мл в основной группе против 5,47 (3,35-7,68) нг/мл, медиана рецепторов - 18,83 (14,98; 25,11) нг/мл против 30,93 (24,68; 33,53) нг/мл. Между данными показателями в этой группе обнаружена отрицательная связь умеренной силы (rs=–0,451; p<0,0004). В основной группе отмечены более высокие значения рН в кардиальном отделе и теле желудка (p<0,05 и p<0,04 соответственно). Длительность контакта забрасываемого содержимого с низким рН (<4) в указанных отделах оказалась больше в группе сравнения (p<0,05). Выявлены независимые от массы тела взаимосвязи уровня лептина с разбросом, индексом агрессивности, максимальным значением рН в кардии и теле желудка и длительностью контакта забрасываемого содержимого с рН менее 4,0 (rs=0,543, p<0,006; rs=0,432, p<0,04; rs=0,431, p<0,04; rs=–0,450, p<0,03 соответственно), рецепторов к лептину с индексом соотношения рН в кардии и теле желудка, числом рефлюксов более 5 мин в пищеводе и индексом De Meester по данному показателю (rs=0,471, p<0,04; rs=–0,455, p<0,04; rs=–0,454, p<0,04 соответственно). Заключение. ГЭРБ у лиц с ожирением и избыточной массой тела формируется в условиях лептинорезистентности и патологии билиарного тракта, что обусловливает особенности течения заболевания (щелочное, смешанное забрасываемое содержимое) и необходимость индивидуализации терапии.

Topics: Adult; Biliary Tract Diseases; Body Mass Index; Body Weight; Comorbidity; Endoscopy, Digestive System; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin; Risk Factors; Russia; Statistics as Topic

The aim of this prospective study was to evaluate the impact of obesity, determined by different anthropometric measures, on clinical and endoscopic severity of GERD and the relation between serum leptin and clinical and endoscopic severity of GERD in Egyptian patients. The study was carried out at Ain Shams University Hospitals and Theodor Bilharz Research Institute, Cairo, Egypt. A total of 60 patients with clinically and endoscopically evident gastroesophageal reflux disease (GERD) were enrolled in this study as well as 20 healthy subjects matched for age and gender serving as the control group. Patients were divided according to their body mass index (BMI) into two groups: group 1 (n = 30): overweight and obese (BMI ≥ 25 and/or waist-to-height ratio [WHtR] ≥ 0.5) and group 2 (n = 30): normal weight (BMI ≥ 18 to < 25 and/or WHtR ≥ 0.4 to < 0.5). Upper gastrointestinal endoscopy, anthropometric measures, and symptom severity score questionnaire were done for all patients. Serum leptin hormone was assessed for patients and control groups.The evidence revealed statistically significant difference between the two groups in terms of different anthropometric measures (P < 0.00) except the height (P < 0.9), abdominal fat depot equations (P < 0.00), endoscopic findings according to Los Angeles classification (P < 0.001), symptom severity score (P < 0.00), and serum leptin hormone (43.96 ± 23.50 in group 1 vs. 7.5133 ± 8.18294 in group 2 and 6.98 ± 5.90 in the control group) (P = 0.00). Obesity in general and central (abdominal) obesity specifically has significant impact on clinical and endoscopic severity of GERD. Increased leptin hormone level is associated with clinical and endoscopic severity of GERD. Future trial on larger number of patients is emphasized.

Topics: Abdominal Fat; Adult; Anthropometry; Body Height; Body Mass Index; Case-Control Studies; Egypt; Endoscopy, Gastrointestinal; Female; Gastroesophageal Reflux; Healthy Volunteers; Humans; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Severity of Illness Index

AIM OR OBJECTIVE: to examine the levels of leptin and its soluble receptor in the serum of patients with gastroesophageal refluxed disease (GERD) with different weight.. We examined 125 patients with GERD. We asked patients, assessed an anthropometric indices, did a biochemical analysis of blood, ultrasonic studies of abdominal, endoscope examination of the esophagus and stomach, pH monitoring, assessed levels leptin and its soluble receptor. We separated patients in two groups: the main group (n = 105) - patients with overweight and obesity, the comparison group (n = 20) - with normal weight.. Values of waist circumference, the hips, its relationship, level of glucose and triglycerides was higher in main group (p<0, (10) (10)3, p<0,00002, p<0,0096, p<0,02, p<0,008, respectively). Leptin levels in patients with obesity and overweight was significantly higher and the level of its receptors was significantly lower (mediana of leptin levels 29,81 (12,63-45,62) in main group versus 4,13 (3,03-5,79), mediana of leptin's receptors 18,74 (14,98-25,11) versus 31,82 (27,81-34,43), respectively). Between these indicators in main group was revealed negative correlation of moderate strength (rs= (-0,452), p<0,0004). In group with overweight and obesity a fairly significant correlation between the level of adipokines and severity of symptoms of GERD were found: negative correlation of moderate intensity between leptin and severity of dysphagia (rs= (-0,259), p<0,05) and positive correlation of moderate intensity between leptin's receptor and severity of belching (rs= (-0,295), p<0,02). As well as a fairly significant positive association of moderate strength between leptin levels and the maximum value of pH in the stomach (rs= (-0,499), p<0,03) and between leptin's receptor and index relationship of pH in the cardia of the stomach to the body (rs= (-0,505), p<0,04) were found.. leptinresistance in individuals with overweight and obesity is associated with features of GERD.

Topics: Female; Gastroesophageal Reflux; Humans; Leptin; Male; Obesity; Receptors, Leptin

Topics: Adipokines; Adiponectin; Barrett Esophagus; Female; Gastroesophageal Reflux; Humans; Insulin; Leptin; Male; Serum

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.. One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett's esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.. All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile), 80.1 (49.8-108.3) vs. 99.4 (65.8-131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0-120.8) vs. 32.8 (28.7-84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6-9.3) vs. 9.9 (9.6-10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1-9.2) vs. 9.2 (7.1-11.2) μg/ml, p = 0.026] than those without BE.. Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.

Topics: Adiponectin; Adult; Barrett Esophagus; Female; Gastroesophageal Reflux; Ghrelin; Heartburn; Humans; Leptin; Male; Middle Aged; Peptide YY; Surveys and Questionnaires

Risk prediction models for Barrett's esophagus (BE) have been developed using multiple demographic and clinical variables, but their predictive performance has been modest. Adding a multibiomarker risk score may improve discriminatory ability.. We used data from 141 patients with definitive BE and 138 controls participating in a case-control study at the Michael E. DeBakey Veterans Affairs Medical Center (Houston, TX) (97% men, 65% of controls were white, and 89% of cases were white). We derived and compared 3 prediction models. Model 1 included only gastroesophageal reflux disease (GERD) frequency and duration; model 2 included GERD frequency and duration, age, sex, race, waist-to-hip ratio, and Helicobacter pylori status; and model 3 included the variables in model 2 as well as a multibiomarker risk score based on serum levels of interleukin (IL)12p70, IL6, IL8, IL10, and leptin. We assessed their predictive accuracy in terms of discrimination using the area under the receiver operating characteristic curve and calibration analyses.. The multibiomarker risk score was associated significantly with risk for BE. Compared with persons with a score of 0, persons with a score of 3 or higher had a greater than 10-fold increased risk for BE (biomarker risk score, ≥3; odds ratio, 11.9; 95% confidence interval, 4.06-34.9; P trend < .001). Risk prediction using the multibiomarker score in conjunction with demographic and clinical features improved discrimination compared with using only GERD frequency and duration (area under the receiver operating characteristic curve, 0.85 vs 0.74; P = .01).. Based on data from a case-control study of predominantly white male veterans, a risk prediction model including a multibiomarker score, derived from serum levels of cytokines and leptin, as well as GERD frequency and duration, age, sex, race, waist-to-hip ratio, and H pylori infection, can identify persons in this population with BE more accurately than previous methods.

Topics: Adult; Aged; Aged, 80 and over; Anthropometry; Barrett Esophagus; Biomarkers; Case-Control Studies; Cytokines; Demography; Female; Gastroesophageal Reflux; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Risk Assessment

Insulin and leptin have proliferative and anti-apoptotic effects. Ghrelin promotes gastric emptying and secretion of growth hormone and inhibits inflammation. We assessed whether diabetes mellitus and serum levels of insulin, leptin, and ghrelin are associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus.. We conducted a case-control study in 822 men undergoing colorectal cancer screening who were recruited to also undergo upper endoscopy. We identified 70 with Barrett's esophagus; 80 additional men with Barrett's esophagus were recruited shortly after their clinical diagnoses. Serum levels of insulin, leptin, and ghrelin were assayed in all 104 fasting men with Barrett's esophagus without diabetes and 271 without diabetes or Barrett's esophagus. Logistic regression was used to estimate the effects of diabetes and levels of insulin, leptin, and ghrelin on GERD and Barrett's esophagus.. Among men with GERD, diabetes was inversely associated with Barrett's esophagus (adjusted odds ratio [OR] = 0.383; 95% confidence interval [CI]: 0.179-0.821). Among nondiabetics, hyperinsulinemia was positively associated with Barrett's esophagus, but the association was attenuated by adjustment for leptin and ghrelin. Leptin was positively associated with Barrett's esophagus, adjusting for obesity, GERD, and levels of insulin and ghrelin (OR for 3(rd) vs 1(st) tertile = 3.25; 95% CI: 1.29-8.17); this association was stronger in men with GERD (P = .01 for OR heterogeneity). Ghrelin was positively associated with Barrett's esophagus (OR for an increment of 400 pg/mL = 1.39; 95% CI: 1.09-1.76), but inversely associated with GERD (OR for 3(rd) vs 1(st) tertile = 0.364; 95% CI: 0.195-0.680).. Based on a case-control study, leptin was associated with Barrett's esophagus, particularly in men with GERD. Serum insulin level was associated with Barrett's esophagus, but might be mediated by leptin. Serum ghrelin was inversely associated with GERD, as hypothesized, but positively associated with Barrett's esophagus, contrary to our hypothesis. Additional studies are needed in men and women to replicate these findings.

Topics: Aged; Barrett Esophagus; Case-Control Studies; Diabetes Complications; Endoscopy, Gastrointestinal; Gastroesophageal Reflux; Ghrelin; Humans; Incidence; Insulin; Leptin; Logistic Models; Male; Middle Aged; Risk Factors

Obesity is associated with gastroesophageal reflux disease (GERD). Leptin is a hormone which controls appetite and energy homeostasis. Alterations of its level in humans have been linked with obesity and related carcinogenesis. We postulated that the leptin level in plasma or tissues might be different according to the phenotype of GERD. We evaluated this hormone in patients with non-erosive reflux disease (NERD) and reflux esophagitis (RE) with demographic characteristics to confirm the postulation.. The patients with typical GERD symptoms such as acid regurgitation and heartburn were prospectively enrolled and evaluated. The demographic data included body mass index, waist circumference, smoking, and the consumption of coffee. Rapid urease test was done to evaluate the status of Helicobacter pylori infection. We measured plasma leptin level along with the tissue level, which was obtained from the fundus of stomach.. A total of 44 patients were evaluated (RE 20 cases, NERD 24 cases). No demographic data was different between the two groups, except waist circumference (mean 88.6 cm in RE, 80.9 cm in NERD, p=0.006), smoking (45% in RE, 12.5% in NERD, p=0.021) and coffee consumption (85% in RE, 50% in NERD, p=0.025). The level of plasma leptin was not different between the two groups. The level of tissue leptin was also not different between the two groups with an increasing tendency in RE (mean 32.5 ng/mL vs. 28.0 ng/mL in NERD).. We could not find any association between plasma and tissue leptin levels and the phenotype of GERD. However, increasing tendency in RE could afford to further studies in near future.

Topics: Adult; Aged; Body Mass Index; Coffee; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Middle Aged; Obesity; Phenotype; Smoking; Waist Circumference

Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis.. To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia.. From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay.. Of 269 individuals enrolled, 105 were Helicobacter pylori-negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123-333) pg/mg) compared with normal (126 (78-221) pg/mg) or inflamed (114 (76-195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus.. Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression.

Topics: Barrett Esophagus; Endoscopy, Digestive System; Esophagitis; Esophagus; Female; Gastric Mucosa; Gastroesophageal Reflux; Humans; Leptin; Male; Metaplasia; Middle Aged; Receptors, Leptin; Retrospective Studies; Sensitivity and Specificity

Obesity is associated with increased risks of Barrett's oesophagus and oesophageal adenocarcinoma. Alterations in serum leptin and adiponectin, obesity-related cytokines, have been linked with several cancers and have been postulated as potential mediators of obesity-related carcinogenesis; however, the relationship with Barrett's oesophagus remains unexplored.. Serum leptin and adiponectin concentrations were measured on two subsets of participants within a case-control study conducted in Brisbane, Australia. Cases were people aged 18-79 years with histologically confirmed Barrett's oesophagus newly diagnosed between 2003 and 2006. Population controls, frequency matched by age and sex to cases, were randomly selected from the electoral roll. Phenotype and medical history data were collected through structured, self-completed questionnaires. Odds ratios (OR) and 95% CI were calculated using multivariable logistic regression analysis.. In the pilot analysis (51 cases, 67 controls) risks of Barrett's oesophagus were highest among those in the highest quartile of serum leptin (OR 4.6, 95% CI 0.6 to 33.4). No association was seen with adiponectin. In the leptin validation study (306 cases, 309 controls), there was a significant threefold increased risk of Barrett's oesophagus among men in the highest quartile of serum leptin (OR 3.3, 95% CI 1.7 to 6.6) and this persisted after further adjustment for symptoms of gastro-oesophageal reflux (OR 2.4, 95% CI 1.1 to 5.2). In contrast, the risk of Barrett's oesophagus among women decreased with increasing serum leptin concentrations.. High serum leptin is associated with an increased risk of Barrett's oesophagus among men but not women. This association is not explained simply by higher body mass or gastro-oesophageal reflux among cases. The mechanism remains to be determined.

Topics: Adiponectin; Adolescent; Adult; Age Distribution; Aged; Barrett Esophagus; Biomarkers; Body Mass Index; Female; Gastroesophageal Reflux; Humans; Leptin; Male; Middle Aged; Pilot Projects; Sex Distribution; Sex Factors

In the Western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastro-oesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However, there is no plausible biological mechanism of association between H. pylori, obesity, and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake, and body composition, was studied in H. pylori positive asymptomatic subjects.. Plasma ghrelin, leptin, and gastrin were measured for six hours after an overnight fast, before and after cure of H. pylori in 10 subjects. Twenty four hour intragastric acidity was also assessed.. After cure, median (95% confidence intervals) integrated plasma ghrelin increased from 1160.5 (765.5-1451) pg/ml x h to 1910.4 (1675.6-2395.6) pg/ml x h (p=0.002, Wilcoxon's rank sum test), a 75% increase. This was associated with a 14% increase in 24 hour intragastric acidity (p=0.006) and non-significant changes in leptin and gastrin. There was a significant positive correlation between plasma ghrelin and intragastric acidity (r(s) 0.44, p=0.05, Spearman's rank correlation).. After H. pylori cure, plasma ghrelin increased profoundly in asymptomatic subjects. This could lead to increased appetite and weight gain, and contribute to the increasing obesity seen in Western populations where H. pylori prevalence is low. This plausible biological mechanism links H pylori, through increasing obesity and GORD, to the increase in oesophageal adenocarcinoma observed in the West.

Topics: Adenocarcinoma; Adult; Esophageal Neoplasms; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Peptide Hormones; Radioimmunoassay