We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes.
Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately.
We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group.
A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

BACKGROUND: Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.
METHODS: A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary.
RESULTS: The intention-to-treat (ITT) population did not meet the prespecified primary endpoint at week 12 (difference in nausea severity change drug vs placebo; P = .741) or prespecified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points (weeks 2-4). In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at week 12.
CONCLUSIONS: Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. (ClincialTrials.gov, Number: NCT04028492).

Gastroparesis is a chronic and debilitating gastrointestinal disorder with few medical treatment options. Traditional surgical management has involved laparoscopic pyloromyotomy or gastric stimulation. In recent years, gastric peroral endoscopic myotomy (GPOEM) has become an attractive, less invasive option for patients with refractory gastroparesis. There is little information on the long-term clinical success of GPOEM in patients with refractory gastroparesis. This systematic review aims to evaluate the data on this procedure\'s long-term clinical efficacy and safety. A comprehensive literature review was done in PubMed, EMBASE, Ovid, and Google Scholar databases from the date of earliest entry in May 2017 up to August 15, 2022. The Gastroparesis Cardinal Symptom Index (GCSI) score, adverse reaction, and length of stay were analyzed. Eleven studies were eligible for inclusion (900 patients), seven of the studies were retrospective, while four were prospective. The GCSI is a 6-point Likert scale questionnaire that assesses improvement in gastroparesis. An average decrease of GCSI by 1 point compared to baseline GCSI for all patients (described as clinical success) was found in 662 patients out of 713 (92.8%) at one-year follow-up, 421 out of 460 (91.5%) at two-year follow-up, 270 out of 270 (100%) at three-year follow-up, and 102 out of 102 (100%) at four-year follow-up. Adverse events occurred in 62 out of 835 patients (in nine studies), with two of the most frequent being bleeding and mucosal tears. GPOEM is an effective and safe treatment option for patients with refractory gastroparesis, with symptom improvement noted up to four years postoperatively.

Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.

Gastroparesis (GP) is hallmarked by nausea, vomiting, and early satiety. While dietary and medical therapy are the mainstay of treatment, surgery has been used to palliate symptoms. Two established first-line surgical options are gastric electrostimulation (GES) and pyloric procedures (PP) including pyloroplasty or pyloromyotomy. We sought to compare these modalities\' improvement in Gastroparesis cardinal symptom index (GCSI) subscores and potential predictors of therapy failure.
All patients undergoing surgery at a single institution were prospectively identified and separated by surgery: GES, PP, or combined GESPP. GCSI was collected preoperatively, at 6 weeks and 1 year. Postoperative GCSI score over 2.5 or receipt of another gastroparesis operation were considered treatment failures. Groups were compared using Pearson\'s chi-squared and Kruskal-Wallis one-way ANOVA.
Eighty-two patients were included: 18 GES, 51 PP, and 13 GESPP. Mean age was 44, BMI was 26.7, and 80% were female. Preoperative GCSI was 3.7. The PP group was older with more postsurgical gastroparesis. More patients with diabetes underwent GESPP. Preoperative symptom scores and gastric emptying were similar among all groups. All surgical therapies resulted in a significantly improved GCSI and nausea/vomiting subscore at 6 weeks and 1 year. Bloating improved initially, but relapsed in the GES and GESPP group. Satiety improved initially, but relapsed in the PP group. Fifty-nine (72%) had surgical success. Ten underwent additional surgery (7 crossed into the GESPP group, 3 underwent gastric resection). Treatment failures had higher preoperative GCSI, bloating, and satiety scores. Treatment failures and successes had similar preoperative gastric emptying.
Both gastric electrical stimulation and pyloric surgery are successful gastroparesis treatments, with durable improvement in nausea and vomiting. Choice of operation should be guided by patient characteristics and discussion of surgical risks and benefits. Combination GESPP does not appear to confer an advantage over GES or PP alone.

Postsurgical gastroparesis is recognized as a gastrointestinal dysfunction syndrome following foregut surgery. Gastric peroral endoscopic myotomy (G-POEM) is suggested as a minimally invasive therapy for gastroparesis. But the long-term efficacy and safety of G-POEM in treating postsurgical gastroparesis are rarely explored.
The primary outcomes included the symptomatic improvement based on gastroparesis cardinal symptoms index (GCSI) and the improvement of gastric emptying. The secondary outcomes included the improvement of gastroesophageal reflux symptoms and complications of G-POEM.
The severity of postsurgical gastroparesis was not associated with the onset time and the course of the disease. G-POEM significantly reduced GCSI throughout the follow-up period (p < 0.0001). For different anastomotic site, a significant improvement of GCSI was found at 6 month post-G-POEM (F4,165 = 74.18, p < 0.0001). Subscale analysis of GCSI showed that nausea/vomiting, post-prandial fullness/early satiety, and bloating were improved significantly at 6-month post-G-POEM (p < 0.0001, respectively). Half-emptying and whole-emptying time were significantly shortened in patients with different anastomotic site post-G-POEM (half-emptying time: F3,174 = 65.44, p < 0.0001; whole-emptying time: F3,174 = 54.85, p < 0.0001). The emptying of ioversol was obviously accelerated after G-POEM. GCSI wasn\'t related to pyloric length, pyloric diameter, and thickness of pyloric wall. GERDQ was also used to evaluate the clinical efficacy of G-POEM. For each time points, GERDQ didn\'t differ significantly in patients with different anastomotic site (F4,104 = 0.8075, p = 0.5231). For patients with different anastomotic site, GERDQ was improved significantly at different time points (F4,104 = 59.11, p < 0.0001). The higher the esophageal anastomotic site was, the faster G-POEM improved the symptoms of gastroesophageal reflux. No one required re-hospitalization for any complication.
G-POEM is a minimally invasive therapy with long-term effectiveness and safety in treating postsurgical gastroparesis.

Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis.
We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018. Participants were randomly assigned to groups given oral tradipitant 85 mg (n = 77) or placebo (n = 75) twice daily for 4 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. The primary outcome from the intent-to-treat analysis was change from baseline to week 4 in average nausea severity, measured by the Gastroparesis Core Symptom Daily Diary.
Patients receiving tradipitant had a significant decrease in nausea score (reduction of 1.2) at week 4 compared with placebo (reduction of 0.7) (P = .0099) and a significant increase in of nausea-free days at week 4 (28.8% increase on tradipitant vs 15.0% on placebo; P = .0160). Patients with nausea and vomiting at baseline (n = 101) had an even greater decrease in nausea in when given tradipitant (reduction of 1.4) compared with those given placebo (reduction of 0.4) (P < .0001), as well as an increase in nausea-free days at week 4 (32.3% improvement on tradipitant vs 7.6% on placebo; P = .0003). The average nausea score was 1 or less at week 4 in 32.9% of patients given tradipitant compared with 11.8% of patients given placebo (P = .0013). A greater than 1-point improvement in Gastroparesis Cardinal Symptom Index score was observed in 46.6% of patients given tradipitant compared with 23.5% of patients given placebo (P = .0053).
Tradipitant resulted in statistically and clinically meaningful improvements in nausea and reduced vomiting, compared with placebo, in patients with idiopathic or diabetic gastroparesis. ClinicalTrials.gov, Number: NCT02970968.

Symptoms of gastroparesis (Gp) can fluctuate at different times of the day. Our aims are (1) To characterize Gp symptom variability throughout the day and in relation to meals and (2) to compare the daily symptom variability in subtypes of Gp-diabetic gastroparesis (DGp) and idiopathic gastroparesis (IGp).
Patients with Gp filled Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) and completed a modified GCSI-DD seven times a day (GCSI-Throughout the Day [GCSI-TTD]; before and after meals, and before going to bed) over a 2-week period. KEY RESULTS: A total of 44 patients participated (86% females), including 29 (66%) with IGp, 13 (30%) with DGp, and 2 (4%) with postsurgical Gp. Using the GCSI-TTD, patients with Gp reported significant postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. Patients also had progressive worsening of the overall symptom severity, early satiety, stomach fullness, and abdominal pain during the day; however, nausea severity did not differ during the day. Number of vomiting and retching episodes did not show significant variations postprandially or during the day. Patients with IGp had greater symptom severity throughout the day and greater postprandial increase in symptoms compared to patients with DGp. CONCLUSIONS AND INFERENCES: Patients with Gp experience postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. These symptoms also progressively worsen during the day, except for the severity of nausea which persists throughout the day. Understanding the symptom variability in patients with Gp throughout the day and postprandially may be useful in treatment of patients with Gp.

Lewy body disease is postulated, by the Braak model, to originate in the enteric nervous system, before spreading to the central nervous system. Therefore, a high prevalence of gastroparesis symptoms would be expected in prodromal dementia with Lewy bodies (DLB) and be highest in those with a dopaminergic deficit on imaging. The aim of this study was to explore whether gastroparesis symptoms are an early diagnostic marker of prodromal DLB and explore the relationship between symptoms and dopaminergic imaging findings on FP-CIT SPECT.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 48 with MCI with suspected Lewy body disease (MCI-LB) and 27 with MCI with suspected Alzheimer\'s disease (MCI-AD). All patients completed the Gastroparesis Cardinal Symptom Index (GSCI) questionnaire and also underwent FP-CIT [123 I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging.
At least one symptom suggestive of gastroparesis was reported in 48% (n = 23) MCI-LB vs 37% MCI-AD (n = 10) (P = 0.36). Rates of definite symptoms of gastroparesis, as defined by a GCSI total score ≥ 1.90, were rare and rates in MCI-LB were not different from MCI-AD (6% vs 0%, p = 0.55). After adjusting for gender differences between groups, no difference in gastroparesis symptom prevalence (2.27 vs 0.81 P = 0.05) or severity score (0.62 vs 0.28, p = 0.28) was noted between normally and abnormally visually rated FP-CIT SPECT scans.
The GCSI is not a useful tool for differentiating MCI-LB from MCI-AD. A low rate of definite gastroparesis was detected in prodromal DLB. No association was found between gastroparesis symptoms and FP-CIT SPECT findings.

The GCSI questionnaire measures symptoms of gastroparesis (GP). Symptoms of FD overlap with GP. The ability of the GCSI to discriminate FD from GP is unknown.
By prospectively evaluating functional dyspepsia (FD) patients, we aimed to evaluate the ability of the Gastroparesis Cardinal Symptom Index (GCSI) to: (1) distinguish FD from GP; (2) predict symptom severity, anxiety, and depression; (3) correlate symptoms with gastric emptying.
FD patients (Rome III criteria) were identified, and upper endoscopy and gastric emptying scan (GES) data recorded. A total of 254 patients were mailed a questionnaire evaluating demographics, FD symptoms, mental well-being; the GCSI was included.
One hundred and twenty-three patients responded; of them, 75% were women and mean age was 49 (15 SD) years. 44.7% were categorized as postprandial distress subtype (PDS), 34.1% were epigastric pain subtype (EPS), and 21.1% were mixed type. The mean GCSI score was 2.02 (1.1 SD), slightly lower than historical GP controls (2.26-2.56). Mixed EPS-PDS subtype had the lowest GCSI scores (1.79; 0.91 SD). Bloating was the highest GCSI subscore (2.70; 1.53 SD), followed by fullness (2.31; 1.39 SD) and nausea (1.08; 1.19 SD). The GCSI total score did not correlate with anxiety and depression scores or with 4-h gastric emptying.
In this population of FD patients, GCSI scores were slightly lower than historical gastroparesis control patients, although within the reported range. These results suggest that the GCSI cannot accurately distinguish FD patients from GP patients. A more specific questionnaire is needed to aid in the diagnosis and management of these distinct gastrointestinal disorders.