Introduction

The prevalence of functional dyspepsia (FD) and gastroparesis in diabetic patients remains unknown. A high prevalence of gastroparesis has been reported in diabetic patients reaching up to 5%.¹ However, recent consensus specified the symptom pattern for gastroparesis, with nausea and/or vomiting as predominant symptoms, now defined as “gastroparesis-like symptoms” (GPLS).² The global prevalence of GPLS has been estimated to reach only 1.2% in diabetic patients, but type 1 and type 2 diabetes were not assessed separately.²

Aims & Methods

We aimed to assess the prevalence and burden of FD and GPLS in primary care patients with diabetes, comparing patients with type 1 and type 2 diabetes. An online survey was addressed to diabetic patients through general practitioners and diabetic patient associations. The survey included the Rome IV questionnaire and the Patient Assessment of Gastro-Intestinal Disorders-Symptom Severity Index (PAGI-SYM) for upper gastro-intestinal symptoms. Anxiety, depression, somatization, and quality of life were also assessed by specific questionnaires (Generalized Anxiety Disorder GAD-7, Patient Health Questionnaire PHQ-9, PHQ-15, and PAGI-QoL questionnaires respectively).

Results

A total of 216 patients completed the questionnaires, among which 146 had type 1 diabetes, and 68 had type 2 diabetes, (2 patients did not know their type of diabetes). The median age of the population was 56 (50-61) years old, with 134 female patients (61.8%). The prevalence of FD was 13.0% with no difference between the 2 groups. The prevalence of GPLS reached 4.2% and was significantly higher in patients with type 2 diabetes (8.9% vs 2.1%; p=0.03). The burden of upper gastro-intestinal symptoms and their impact on quality of life was higher in type 2 diabetes patients with higher PAGI-SYM and PAGI-QoL scores while anxiety and somatization were not different between type 1 and type 2 diabetes patients (see Table). Overall, patients with GPLS had higher anxiety (9 vs 3; p=0.003), depression (12 vs 3; p=0.001) and somatization scores (16 vs 6; p<0.001) than patients without. Compared to patients with FD without GPLS, GPLS patients had numerically higher but not statistically different scores for symptom severity (51 vs 28; p=0.46), anxiety (9 vs 7; p=0.29), depression (12 vs 7; p=0.07), somatization (16 vs 11.5; p=0.16) and quality of life scores (52 vs 24; p=0.16).

Conclusion

This study confirms that the prevalence of GPLS seems to be higher in diabetic patients compared to available population data, especially in patients with type 2 diabetes. The impact of the symptoms was similar to the impact of FD in this population. Further studies are required to assess the prevalence of delayed gastric emptying in diabetic type 1 and 2 patients with GPLS.

References

1. Choung RS, Locke GR, Schleck CD, et al. Risk of Gastroparesis in Subjects with Type 1 and 2 Diabetes in the General Population. Am J Gastroenterol 2012;107:82-88.
2. Huang I-H, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J 2022;10:888-897.

Introduction

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Individuals with coeliac disease (CeD) commonly complain of persistent symptoms despite adhering to a gluten free diet (GFD). We analysed baseline data from the prospective pseudonymized German CeD Registry to identify factors associated with ongoing complaints.

Aims & Methods

​​​​​​After written informed consent, participants self-reported demographic, clinical and healthcare related information at baseline and yearly thereafter. Symptoms before diagnosis and during the four weeks prior to completing the baseline questionnaire were retrospectively assessed. Factors associated with symptoms after at least one year of gluten-free diet (GFD) were evaluated by multivariate logistic regression.

Results

From 11/2019 to 10/2021, 2164 participants provided baseline data: 78% were female, median age 36 years (range 1.1 to 93.2), median time since diagnosis 6.3 years (0 to 58.7), and median diagnostic delay (time from first symptom to diagnosis) 2.2 years (0 to 64.8). Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Individuals diagnosed in adulthood were more symptomatic compared to paediatric patients. Although 93.4% of participants reported improvement after diagnosis, a substantial proportion of those keeping a GFD >1year (n=1861, 86% of cohort) had ongoing symptoms. Factors associated with regularly experiencing above symptoms included female gender, having the same symptom before diagnosis, feeling insufficiently informed by their physician about CeD and implications for their daily life, and age at diagnosis (per decade), but not time since diagnosis (table).

Conclusion

Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care. In this large cohort of patients with CeD we identified factors associated with persistence of symptoms despite keeping a GFD for at least one years. Early diagnosis, providing comprehensive education after confirmed diagnosis, and ensuring strict dietary adherence are pivotal for symptom resolution. A population-based mass-screening for CeD in childhood should be further explored. Implementing a multifaceted approach will enhance care for individuals with CeD and ultimately improve long-term health and well-being.

Introduction

Approximately 15-19% of patients suffering from irritable bowel syndrome (IBS) have an eating disorder (ED) based on a screening score or dietary assessment (1). Avoidant/restrictive food intake disorder (ARFID), a long-recognised eating disorder in children, is now recognised in adults. In a Swedish study, 13.2% of patients suffering from IBS reported severe dietary avoidance or restriction, suggestive of ARFID (2). A screening questionnaire for this disorder has recently been validated in French (NIAS-Fr, for Nine Item ARFID Screen in French) (3).

Aims & Methods

This study aims to assess the prevalence of ARFID in IBS in France, by comparing the NIAS-Fr questionnaire and the assessment by a specialised dietitian, and to look for links between its presence and the clinical phenotype of patients. This study was conducted between February and September 2024 in consecutive patients suffering from IBS and evaluated in a multidisciplinary day hospital structure. Clinical characteristics (age, gender, BMI, IBS subtype and its severity [IBS-SSS], presence of functional dyspepsia, diet and disease duration) and presence of ARFID (clinically or one abnormal NIAS-Fr subscale) were collected. A dietitian assessed the presence of “clinical ARFID”. The NIAS subscales allow for the diagnosis of patients as “picky eaters” (score ≥10), with “poor appetite” (score ≥9) and/or with a “fear of eating” (score ≥10). Patients with a history of ED diagnosed by a psychiatrist and/or an abnormal ED screening score (SCOFF ≥ 3 and/or global EDE-Q8 ≥ 4.0) were excluded from the analysis.

Results

Of the 95 patients with IBS according to Rome IV, 55 (57.9%) had at least one positive NIAS-Fr subscale, with 10 (10.5%) having an abnormal “picky eater” subscale, 16 (16.8%) an abnormal “poor appetite” subscale, and 49 (51.6%) an abnormal “fear of eating” subscale. Of these 95 patients, 15 were excluded from the analysis because of a history of eating disorders or an abnormal screening score. We therefore included 80 patients for analysis (77.5% women; mean age 48.5 ± 16.8 years, BMI 22.6 ± 4.6 kg/m²; 40.0% IBS-D, 38.8% IBS-C, and 20.0% IBS-M; 51.3% had associated dyspepsia; 62.5% were on a special diet at the time of assessment). The mean IBS-SSS score was 319.5 ± 88.2 points (severe forms in 61.2%). Among these 80 patients, 43 (53.8%) had at least one positive NIAS-Fr subscale, including 10.0% of "picky eaters," 16.3% of "poor appetite," and 48.8% of "fear of eating." Patients with at least one positive NIAS-Fr subscale had more frequent functional dyspepsia than those with a negative NIAS (65.1 vs. 35.1%, p = 0.013), but there were no differences in the other parameters assessed. According to the dietitian's assessment, 19 (23.8%) patients in our cohort had clinical ARFID, i.e., 44.2% of those with at least one positive NIAS-Fr subscale. In an IBS population, the specificity of the NIAS-Fr questionnaire for diagnosing clinical ARFID was 55.8% (95% CI: 41.1-69.6). None of the assessed parameters distinguished patients with and without clinical ARFID (p > 0.05).

Conclusion

ARFID symptoms are found in more than half of IBS patients treated in a tertiary care centre based on an abnormal NIAS-Fr screening questionnaire, after excluding other eating disorders. These patients frequently have associated functional dyspepsia and a normal BMI. Based on a dietary assessment, clinical ARFID is found in approximately one-quarter of IBS patients. The specificity of the NIAS-Fr in IBS is too low to allow a diagnosis of ARFID in this population.

References

(1) Wuestenberghs et coll. Intérêt du dépistage des troubles du comportement alimentaire au cours du syndrome de l’intestin irritable. JFHOD 2024 (number 000694)
(2) Melchior et coll. Food Avoidance and Restriction in Irritable Bowel Syndrome: Relevance for Symptoms, Quality of Life and Nutrient Intake. Clin Gastroenterol Hepatol. 2022;20(6):1290-1298.e4.
(3) Van Ouytsel et coll. Translation of the nine item avoidant/restrictive food intake disorder screen (NIAS) questionnaire in French (NIAS-Fr). Neurogastroenterology & Motility 2024 ; 36 (4) : e14757.

Disclosure

Nothing to disclose.

Introduction

Intestinal ischemia-reperfusion injury (IRI) is a life-threatening condition caused by an abrupt obstruction of mesenteric blood flow. Reestablishing blood flow (reperfusion) is necessary to save intestinal tissue but unintentionally exacerbates damage induced by ischemia. Mitochondria are sensitive to IRI; if damaged, they release cytotoxic molecules that can aggravate injury. Therefore, removal of damaged mitochondria is essential for cellular survival. The selective clearance of mitochondria via autophagy, mitophagy, has been reported to protect against IRI in other organs, but its role in the intestine remains unknown.

Aims & Methods

The main objective of this study was to assess mitochondrial damage and evaluate signs of mitophagy in response to hypoxia-reoxygenation in a human small intestinal organoid (SIO) model and the differences therein between crypt-like (CL) and villus-like (VL) organoids. Both SIOs phenotypes were exposed to hypoxia-reoxygenation, and mitochondrial damage was assessed by live-cell imaging of mitochondrial membrane potential using fluorescent dye tetramethylrhodamine methyl ester (TMRM). In addition, ultrastructural changes in mitochondria were evaluated by transmission electron microscopy (TEM). Finally, mitochondrial content, autophagy, and mitophagy markers were assessed using quantitative PCR (qPCR) and Western blot.

Results

A drastic decrease in TMRM fluorescence, indicating impaired mitochondrial activity, was mainly observed in VL organoids and not in CL organoids. Mitochondrial ultrastructural changes were observed in both phenotypes, including mitochondrial swelling and disrupted cristae following hypoxia, whereas after 480 minutes reoxygenation, mitochondria exhibited a tubular or small round shape. Mitochondrial content markers were decreased in both organoid phenotypes following hypoxia-reoxygenation. Most importantly, only CL organoids showed a significant increase in autophagy and mitophagy markers.

Conclusion

Mitochondria of VL organoids are more severely damaged by hypoxia-reoxygenation, whereas CL organoids might be protected by inducing mitophagy. The occurrence of mitophagy is currently further validated with live-cell imaging.

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce weight loss, and have been associated with an overall decreased risk of esophageal cancer. Obesity is strongly associated with esophageal adenocarcinoma and substantial weight loss may decrease the risk of this malignancy, whereas weight loss does not decrease the risk of esophageal squamous cell carcinoma. We examined the hypotheses that GLP-1RA treatment decreases the risk of esophageal adenocarcinoma.

Aims & Methods

This population-based case-control study included all cases of esophageal adenocarcinoma and esophageal squamous cell carcinoma in adults who had dispensed medication for type 2 diabetes in Denmark (2007-2020), Finland (2011-2018), Iceland (2009-2019), Norway (2007-2019), or Sweden (2007-2020). For each case participant, >10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from well-validated nationwide health-data registries with prospectively collected data. Multivariable logistic regression provided odds ratios (OR) for esophageal adenocarcinoma and esophageal squamous cell carcinoma with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, obesity, alcohol overconsumption, and tobacco smoking.

Results

This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with non-users (adjusted OR 1.3, 95% CI 1.1-1.5). However, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8).

Conclusion

Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. Confounding by indication may have been the most important, or even the sole, contributor to the decreased risk of esophageal squamous cell carcinoma observed, although anticarcinogenic mechanisms of GLP-1RAs other than weight loss cannot be ruled out.