Gastroparesis

Gastric emptying is a major determinant of postprandial blood glucose, accounting for ~35% of variance in peak glucose in both healthy individuals and those with type 2 diabetes. Gastric emptying is frequently disordered in individuals with diabetes (both abnormally delayed and accelerated). Delayed gastric emptying, i.e. diabetic gastroparesis, may be linked to upper gastrointestinal symptoms for which current treatment remains suboptimal; pharmacological acceleration of delayed emptying is only weakly associated with symptom improvement. Accordingly, the relationship between symptoms and delayed gastric emptying is not simply 'cause and effect'. In insulin-treated patients, disordered gastric emptying, even when not associated with gastrointestinal symptoms, can cause a mismatch between the onset of insulin action and the availability of absorbed carbohydrate, leading to suboptimal glycaemic control. In patients with type 2 diabetes, interventions that slow gastric emptying, e.g. glucagon-like peptide-1 receptor agonists, reduce postprandial blood glucose. This review focuses on recent insights into the impact of gastric emptying on postprandial blood glucose, effects of diabetes therapy on gastric emptying and the management of disordered gastric emptying in diabetes. In view of the broad relevance of gastric emptying to diabetes management, it is important that future clinical trials evaluating novel therapies that may affect gastric emptying should quantify the latter with an appropriate technique, such as scintigraphy or a stable isotope breath test.

PurposePylorus-preserving pancreatoduodenectomy (PPPD) has been the gold standard for pancreatic head lesion resection for several years. Some studies have noted that it involves more delayed gastric emptying (DGE) than classical Whipple (i.e., pancreatoduodenectomy with antrectomy). Our working hypothesis was that the classical Whipple has a lower incidence of DGE. We aimed to compare the incidence of DGE among pancreatoduodenectomy techniques.MethodsThis pragmatic, randomized, open-label, single-center clinical trial involved patients who underwent classical Whipple (study group) or PPPD (control group). Gastric emptying was clinically evaluated using scintigraphy. DGE was defined according to the International Study Group of Pancreatic Surgery (ISGPS) criteria. The secondary endpoints were postoperative morbidity, length of hospital stay, anthropometric measurements, and nutritional status.ResultsA total of 84 patients were randomized (42 per group). DGE incidence was 50% (20/40, 95% confidence interval (95% CI): 35-65%) in the study group and 62% (24/39, 95% CI: 46-75%) in the control group (p = 0.260). No differences were observed between both groups regarding postoperative morbidity or length of hospital stay. Anthropometric measurements at 6 months post-surgery: triceps fold measurements were 12 mm and 16 mm (p = 0.021). At 5 weeks post-surgery, triceps fold measurements were 13 mm and 16 mm (p = 0.020) and upper arm circumferences were 26 cm and 28 cm (p = 0.030). No significant differences were observed in nutritional status.ConclusionDGE incidence and severity did not differ between classical Whipple and PPPD. Some anthropometric measurements may indicate a better recovery with PPPD.Trial registrationClinicalTrials.gov Identifier: NCT03984734.

Altered gastric accommodation and intestinal morphology suggest impaired gastrointestinal (GI) transit may occur in the Wistar-Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague-Dawley (SD) rats under basal conditions and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor gastric emptying (4 h), small intestine (SI) transit (9 h), and large intestine transit (12 h). Plasma extracts were analyzed by lipid and hydrophilic interaction liquid chromatography (HILIC) and liquid chromatography-mass spectrometry (LC-MS). Cecal microbial composition was determined by Illumina MiSeq 16S rRNA amplicon sequencing and analysis using the QIIME pipeline. Stomach retention of beads was 77% for WKY compared with 35% for SD rats. GI transit was decreased by 34% (9 h) and 21% (12 h) in WKY compared with SD rats. Excluding stomach retention, transiting beads moved 29% further along the SI over 4-9 h for WKY compared with SD rats. Cecal Ruminococcus, Roseburia, and unclassified Lachnospiraceae genera were less abundant in WKY rats, whereas the minor taxa Dorea, Turicibacter, and Lactobacillus were higher. Diglycerides, triglycerides, phosphatidyl-ethanolamines, and phosphatidylserine were lower in WKY rats, whereas cholesterol esters and taurocholic acids were higher. The unexpected WKY rat phenotype of delayed gastric emptying, yet rapid SI transit, was associated with altered lipid and metabolite profiles. The delayed gastric emptying of the WKY phenotype suggests this rat strain may be useful as a model for gastroparesis.NEW & NOTEWORTHY This study reveals that the stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis and rapid small intestine transit, together with metabolic changes consistent with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats. This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model for gastroparesis.

ImportancePatients with gastroparesis who do not respond to medical therapy may require surgical intervention, typically involving pyloroplasty (PP) alone or with implantation of a gastric electrical stimulation (GES) device.ObjectiveTo investigate the outcomes of combining PP with GES in medication-refractory gastroparesis.Design, setting, and participantsThis double-blind randomized clinical trial included patients who had diabetic or idiopathic gastroparesis. Patients from a US academic gastrointestinal motility clinic, who failed medical therapy, were included from January 10, 2017, to September 20, 2023. Patients were followed up for 6 months.InterventionsPatients with refractory gastroparesis underwent simultaneous implantation of GES with PP and were randomized into PP + GES-ON and PP + GES-OFF groups. In the PP + GES-ON group, the GES was turned on after surgery. In the PP + GES-OFF group, the device was kept off for 3 months and then was turned on for the following 3 months.Main outcomes and measuresSymptom scores measured with the Gastroparesis Cardinal Symptom Index (GCSI) and the total symptom score (TSS), gastric emptying, and hospitalization length of stay were recorded and compared at baseline and at 3-month and 6-month follow-up visits. Between-group comparisons at 3 months were performed using the Wilcoxon rank sum test following the intention-to-treat procedure.ResultsThe study included 38 patients with gastroparesis (24 females [63.2%]; mean [SD] age, 46.7 [13.2] years), of whom 31 (81.6%) had diabetic gastroparesis, and 7 (18.4%) had idiopathic gastroparesis. Patients were randomized to the PP + GES-ON (n = 19) or the PP + GES-OFF (n = 19) group. At 3 months, the improvement from baseline in the GCSI (median [IQR] ON: -2.2 [-2.6 to -1.5] vs median [IQR] OFF: -0.9 [-1.8 to -0.4]; median difference, -1.33 [95% CI, -2.34 to -0.33]; P = .01) and the TSS (median [IQR] ON: -15.0 [-16.0 to -8.0] vs median [IQR] OFF: -3.0 [-10.0 to -1.0]; median difference, -12.00 [95% CI, -17.49 to -6.51]; P = .005) was significantly greater in the PP + GES-ON compared with the PP + GES-OFF group. Both groups exhibited significantly faster and similar gastric emptying results compared with the baseline. When the PP + GES-OFF group had GES activated at 3 months, symptoms improved significantly by 6 months (median [IQR] GCSI at 6 months: 1.2 [0.4-2.5] vs at baseline: 3.3 [2.8-4.1]; median [IQR] TSS at 6 months: 8.0 [2.0-10.0] vs at baseline: 18 [14.0-21.0]), achieving results comparable with those patients who had their GES device on for the full 6 months. These results at 6 months were accompanied by a significant reduction in hospital length of stay (median [IQR] at 6 months: 0 [0-2.0] vs at baseline: 4.1 [0-10.1]) and an excellent safety profile.Conclusions and relevanceIn this randomized clinical trial, the combination of GES and PP yielded superior outcomes compared with PP alone, resulting in greater alleviation of gastroparesis symptoms and a reduction in hospitalization, which may enhance patient profiling and optimize decision-making for treatments.Trial registrationClinicalTrials.gov Identifier: NCT03123809.