Kuwelker, Saatchi

AbstractAimsGastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a 13C‐spirulina‐based gastric emptying breath test (GEBT) or scintigraphy predicting the severity of daily symptoms in diabetes mellitus.MethodsGastric emptying, symptoms during a gastric emptying study, either scintigraphy (n = 38) or GEBT (n = 111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms.Key ResultsGastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P < 0.0001). Symptoms during the GEBT (46%) and emptying thalf (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the thalf was insignificant. Patients who reported that one or more symptoms were more severe than the others during the GE study were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary.ConclusionsSymptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.

Abstract Background There is increased recognition of duodenal disturbances (inflammation, altered mucosal protein expression, and chemosensitivity) in functional dyspepsia (FD). Besides sensorimotor functions, enteric submucosal neurons also regulate epithelial ion transport. We hypothesized that duodenal mucosal ion transport and expression of associated genes are altered in FD. Methods Duodenal mucosal ion transport (basal and acetylcholine‐ and glucose‐evoked changes in short‐circuit current [Isc]) and expression of associated genes and regulatory miRNAs were evaluated in 40 FD patients and 24 healthy controls. Results Basal Isc (FD: 88.2 [52.6] μA/cm 2 vs healthy: 20.3 [50.2] μA/cm 2 ; P ≤ .0001), acetylcholine‐evoked Isc (FD: Emax 50.4 [35.8] μA/cm 2 vs healthy: 16.6 [15] μA/cm 2 ; P ≤ .001), and glucose‐evoked Isc responses (FD: E max 69.8 [42.1] μA/cm 2 vs healthy: 40.3 [24.6] μA/cm 2 ; P = .02) were greater in FD than in controls. The Emax for glucose was greater in FD patients on selective serotonin reuptake inhibitors. In FD, the mRNA expression of SLC4A7 and SLC4A4 , which transport bicarbonate into cells at the basolateral surface, and the apical anion exchanger SLC26A3 were reduced (false discovery rate <0.05), the serotonin receptor HTR4 was increased, and the serotonin transporter SLC6A4 was decreased. Selected miRNAs (hsa‐miR‐590‐3p, hsa‐miR‐32‐5p) that target genes associated with ionic transport were upregulated in FD. Conclusions Compared to controls, FD patients had greater baseline and agonist‐evoked duodenal mucosal secretory responses. These findings may be explained by reduced gene expression, which would be anticipated to reduce luminal bicarbonate secretion. The upregulated miRNAs may partly explain the downregulation of these genes in FD.

INTRODUCTION: Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aim was to ascertain whether epigenetic alterations in whole blood discriminate among patients with DM with normal, delayed, and rapid gastric emptying (GE). METHODS: Using the ChIP-seq (chromatin immunoprecipitation combined with next-generation sequencing) assays, we compared the genome-wide enrichment of 3 histone modifications (i.e., H3K4me3, H3K9ac, and H3K27ac) in buffy coats from 20 diabetic patients with gastrointestinal symptoms and normal (n = 6), delayed (n = 8), or rapid (n = 6) GE. RESULTS: Between patients with DM with delayed vs normal GE, there were 108 and 54 genes that were differentially bound (false discovery rate < 0.05) with H3K27ac and H3K9ac, respectively; 100 genes were differentially bound with H3K9ac in patients with rapid vs normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (e.g., CCR3 , CRLF2 , CXCR4 , IL5RA , and IL1RL1 ) and glucose homeostasis ( FBP-1 , PDE4A , and CMKLR1 ). For H3K9ac, the differentially occupied genes were related to T-cell development and function (e.g., ICOS and CCR3 ) and innate immunity ( RELB , CD300LB , and CLEC2D ). Compared with normal GE, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (e.g., TNFRSF25 and CXCR4 ) and genes related to insulin resistance and glucose metabolism. Motif analysis disclosed enrichment of binding sites for transcription factors relevant to the pathogenesis and complications of DM. DISCUSSION: GE disturbances in DM are associated with epigenetic alterations that pertain to dysimmunity, glucose metabolism, and other complications of DM.

AbstractAimsSome patients with upper gastrointestinal symptoms have rapid gastric emptying (GE). We aimed to compare patients with normal and rapid GE and to identify phenotypes among patients with rapid GE.MethodsAmong 2798 patients who underwent GE scintigraphy, we compared patients with normal and rapid GE and separately, patients with rapid GE at 1 hour (GE1), 2 hours (GE2), or both (GE12).ResultsIn 2798 patients, GE was normal (74%), delayed (18%), or rapid (8%). Among 211 patients with rapid GE, patterns were rapid GE1 (48%), 2 hours (17%), or 1 and 2 hours (35%); 42 (20%) had diseases that explain rapid GE. A combination of upper and lower gastrointestinal symptoms (54%) was more common that isolated upper (17%) or lower (28%) gastrointestinal symptoms (P < .001). Constipation was more prevalent in patients with rapid GE 2 (72%) than rapid GE 1 (47%) or rapid GE12 hours (67%) (P < .05). Among 179 diabetes mellitus (DM) patients, 15% had rapid GE, which was not associated with the DM phenotype. By multivariable analysis, insulin therapy (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.15‐0.88), and weight loss (OR, 0.10; 95% CI, 0.01‐0.78) were associated with a lower risk of rapid than normal GE in DM.ConclusionsEight percent of patients undergoing scintigraphy had rapid GE, which is most frequently associated with upper and lower gastrointestinal symptoms; constipation is common. Insulin therapy and weight loss were associated with a lower risk of rapid than normal GE in DM patients.