Abstract
Background & Aims
Idiopathic gastroparesis (IG) is a common but poorly understood condition with significant morbidity. We studied characteristics of patients with IG enrolled in the NIDDK Gastroparesis Clinical Research Consortium Registry.
Methods
Data from medical histories, symptom questionnaires, and 4-hour gastric emptying scintigraphy studies were obtained from patients with IG.
Results
The mean age of 243 IG patients studied was 41 years; 88% were female, 46% were overweight, 50% had acute onset of symptoms, and 19% reported an initial infectious prodrome. Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Predominant presenting symptoms were nausea (34%), vomiting (19%), and abdominal pain (23%). Women had more severe nausea, satiety, constipation and overall gastroparesis symptoms. Patients who experienced acute onset IG had worse nausea than those with insidious onset. Overweight patients had more bloating and gastric retention at 2 hours, but less severe loss of appetite. Patients with severely delayed gastric emptying had worse vomiting, more severe loss of appetite and overall gastroparesis symptoms. Severe anxiety and depression was present in 36% and 18%, respectively. 86% met criteria for functional dyspepsia, primarily postprandial distress syndrome.
Conclusions
IG is a disorder that primarily affects young women, beginning acutely in 50% of cases; unexpectedly, many patients are overweight. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a diverse syndrome that varies by sex, body mass, symptom onset, and delay in gastric emptying.
Keywords: gastroparesis, gastric emptying, nausea, vomiting, functional dyspepsia
INTRODUCTION
Gastroparesis is a chronic gastric motility disorder characterized by delayed gastric emptying (1). Symptoms include early satiety, postprandial fullness, nausea, vomiting and abdominal discomfort. Gastroparesis can occur in several clinical settings, in particular as a complication of diabetes and gastric surgery. In many cases, the underlying cause is not known and the term idiopathic gastroparesis (IG) is used.
IG has significant morbidity, yet its clinical features are poorly characterized since reports have been limited by a relatively small number of patients. IG occurs more commonly in women. Two series of patients with IG published by McCallum et al (2) and Harrell et al (3) suggest that symptom onset and body mass might impact on patient presentation.
The National Insitutes of Diabetes and Digestive and Kidney Diseases (NIDDK) Gastroparesis Registry was established in 2006 in order to enroll a sufficiently large number of patients to elucidate the clinical features of gastroparesis. The aims of this study were to determine clinical and other features of IG and determine their association with gender, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity.
METHODS
The NIDDK Gastroparesis Clinical Research Consortium (GpCRC) is a cooperative network of seven clinical centers and one Data Coordinating Center. The Gastroparesis Registry was implemented as an observational study of patients with gastroparesis (ClinicalTrials.gov Identifier: NCT00398801). The Registry consists of patients meeting specific entry criteria with symptoms of at least 12 weeks duration, delayed gastric emptying on scintigraphy, and no abnormality causing obstruction on upper endoscopy. Registry data at enrollment include detailed history and physical examinations, validated symptom questionnaires, upper endoscopy results (within 1 year of enrollment), 4 hour gastric emptying scintigraphy results (within 6 months of enrollment), and laboratory tests.
During face-to-face interviews with each subject, the study physicians or coordinators completed case report forms including data relating to symptoms, disease profile, associated medical conditions, and medication and supplemental therapies. Patients were questioned about the onset of their gastroparesis symptoms, being either acute or insidious onset, if they had an initial infectious prodrome with resultant chronic GI symptoms, and to specify the infectious prodrome symptoms: upper respiratory flu-like symptoms, food-poisoning symptoms, gastroenteritis, or other. The clinical severity of gastroparesis was graded on a scale originally proposed by Tack et al and reported in the American Neurogastroenterology and Motility Society (ANMS) review on treatment of gastroparesis (4). The severity was graded as grade 1: mild gastroparesis (symptoms relatively easily controlled and able to maintain weight and nutrition on a regular diet); grade 2: compensated gastroparesis (moderate symptoms with only partial control with use of daily medications, able to maintain nutrition with dietary adjustments); grade 3: gastric failure (refractory symptoms that are not controlled with the patient having ER visits, frequent doctor visits or hospitalizations and/or inability to maintain nutrition via oral route).
Each patient filled out the 20 item Patient Assessment of Upper Gastrointestinal Disorders Symptoms Severity Index (PAGI-SYM) questionnaire which assesses symptoms of gastroparesis, dyspepsia, and gastroesophageal reflux disease (5). It includes the nine symptoms of the Gastroparesis Cardinal Symptom Index (GCSI) which asks about nausea, retching, vomiting, stomach fullness, inability to finish meal, excessive fullness, loss of appetite, bloating, and abdominal distension (6,7). The GCSI equals the mean of the nausea/vomiting subscore, postprandial fullness/early satiety subscore, and bloating subscore where: Nausea/vomiting subscore = mean of scores for nausea, retching, and vomiting; Postprandial fullness/early satiety sub-score = mean of scores for stomach fullness, inability to finish meal, excessive fullness, and loss of appetite; and Bloating subscore = mean of scores for bloating and large stomach. The PAGI-SYM also inquires about symptoms of gastroesophageal reflux including daytime heartburn, heartburn lying down, daytime chest discomfort, nighttime chest discomfort, daytime reflux, nighttime reflux, and bitter taste. Patients are asked to assess the severity of their symptoms during the previous two weeks using a 0 to 5 scale where no symptoms = 0, very mild = 1, mild = 2, moderate = 3, severe = 4, and very severe = 5.
Psychological functioning was assessed using the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). BDI is a widely used 21-question multiple-choice self-report inventory that relate to depression, cognition, and physical well-being and is extensively employed to quantify depression in a range of clinical conditions (8,9). Each answer is scored on a scale of 0 to 3. Higher total scores indicate more severe depressive symptoms with 29–63 indicating severe depression (8). The STAI consists of 20 questions relating to state anxiety (a temporary or emotional state) and 20 questions pertaining to trait anxiety (long standing personality trait anxiety with a general propensity to be anxious) and has been well validated (10). A score of >44 denotes significant anxiety.
A portion of the Rome III Diagnostic Questionnaire for Adult Functional GI Disorders relating to functional gastroduodenal disorders and irritable bowel syndrome was administered (11). An analysis program developed by the Rome Foundation was utilized to obtain Rome III diagnoses (http://www.romecriteria.org/rome_iii_sas/).
Gastric emptying scintigraphy was performed using a low-fat, egg white meal with imaging at 0, 1, 2, 4 hours after meal ingestion, as described by a multicenter study (12) and endorsed by the Society of Nuclear Medicine and ANMS (13). This protocol ensures standardized information about delayed gastric emptying across the seven sites. Delayed gastric emptying was graded according to the gastric retention at 4 hours: mild (≤20% gastric retention at 4 hours), moderate (>20 to 35%), and severe (>35%) (13,14).
Laboratory tests obtained on each patient included complete blood count with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP).
Patients were prospectively enrolled at seven centers from January 2007 to March 15, 2010 into the ongoing NIDDK Gastroparesis Registry. This report focuses on patients with IG, that is, patients with delayed gastric emptying scintigraphy > 60% at 2 hours and/or > 10% at 4 hours, and the main reason for gastroparesis evaluation not being from diabetic, postsurgical causes, or other known causes.
Statistical Methods
A set of baseline characteristics including demographic, lifestyle, anthropomorphic, laboratory values, co-morbidities, co-medications, psychological evaluation test scores, gastroparesis specific medical history, gastric emptying scintigraphy results and symptom severity scores from the PAGI-SYM were analyzed in both univariable and multivariable logistic regression analyses to show the pattern of these characteristics among IG patients and to also show variations in these patterns across five major IG patient sub-groups: (1) sex – female vs. male, (2) body mass – overweight vs. normal, (3) symptom onset – acute vs. insidious, (4) severity of delay in gastric retention at 4 hours – mild, moderate or severe, and (5) gastroparesis severity using gastroparesis severity scale and symptom severity based on GCSI score. Univariable results are expressed as mean ± standard deviation (SD) or by percentages, where appropriate. The statistical significance of differences in clinical features within each of the IG sub-groups was tested using either a chi-square test for non-ordered categories, Fisher’s exact test, or a Cochran-Armitage test for trend for ordered categorical features. Continuous features were analyzed using a Wilcoxon rank sum test or a Kruskal-Wallis test (15). A series of six bi-directional stepwise (forward and backward) multiple binary logistic regression analyses were used to determine the independent set of characteristics associated with each of the IG sub-groups. Characteristics identified by either the forward or backward procedures were combined into a single model from which the final set of significant and independent characteristics were selected (16). A P-value of 0.05 was used both for the addition or deletion of candidate characteristics in the stepwise procedures. The results for GCSI were derived from separate analyses which did not include the nine individual symptom scores that are components of the GCSI. All final models for each IG-subgroup were found to have adequate goodness of fit. All P values are two-sided, nominal, with a level of 0.05 considered to be statistically significant.
For analyses, both SAS v9.1 (SAS Institute, Cary, NC) and Stata release 11 (Stata Corp, College Station, TX) statistical software were used (17).
RESULTS
Demographic Information
243 patients with IG were enrolled in the NIDDK Registry at the time of data analysis (March 15, 2010). This represented 61% of the total number of patients with delayed gastric emptying enrolled (243 idiopathic, 131 diabetic, 27 other causes). Of the 243 patients with idiopathic gastroparesis, 214 (88%) were female and 218 (90%) were white (Table 1). At the time of enrollment, the mean age was 41±14 (SD) years with 30% age 30 years or less. Mean BMI was 25.6±6.9 kg/m2 with 8% underweight (BMI<18), 47% normal weight (BMI 18 to <25), 20% overweight (BMI 25 to 30), and 26% obese (BMI>30). One third of the IG patients were well educated with college education or higher and over half had annual incomes of $50K or higher.
Table 1.
Characteristics of idiopathic gastroparesis patients overall and for females and males
| Total (N = 243) |
Females (N = 214) |
Males (N = 29) |
P value† |
||||
|---|---|---|---|---|---|---|---|
| Characteristic | No. | Statistic* | No. | Statistic* | No. | Statistic* | |
| Demographic and lifestyle: | |||||||
| Age at enrollment (years): | 0.49 | ||||||
| 18–30 | 72 | 29.6% | 62 | 29.0% | 10 | 34.5% | |
| 31–44 | 80 | 32.9% | 74 | 34.6% | 6 | 20.7% | |
| 45–59 | 67 | 27.6% | 58 | 27.1% | 9 | 31.0% | |
| 60+ | 24 | 9.9% | 20 | 9.3% | 4 | 13.8% | |
| Average age | 243 | 41.0 ± 14.1 | 214 | 40.9 ± 14.0 | 29 | 41.6 ± 14.9 | 0.78 |
| Race: | 1.00 | ||||||
| White | 218 | 89.7% | 192 | 90.0% | 26 | 90.0% | |
| Black | 16 | 6.6% | 14 | 6.5% | 2 | 6.9% | |
| Other | 9 | 3.7% | 8 | 3.7% | 1 | 3.5% | |
| Married (yes vs no) | 143 | 58.9% | 126 | 58.9% | 17 | 58.6% | 0.97 |
| College degree or higher (yes vs no) | 80 | 32.9% | 71 | 33.2% | 9 | 31.0% | 0.82 |
| Income $50,000+ (yes vs no) | 139 | 57.2% | 122 | 57.0% | 17 | 58.6% | 0.87 |
| Ever smoked regularly‡ (yes vs no) | 81 | 33.3% | 65 | 30.4% | 16 | 55.2% | 0.008 |
| Ever drink (past yr) | 96 | 39.5% | 87 | 40.7% | 9 | 31.0% | 0.32 |
| Anthropometry: | |||||||
| Height (m) | 243 | 1.64 ± 0.08 | 214 | 1.62 ± 0.06 | 29 | 1.76 ± 0.07 | <0.001 |
| Weight (kg) | 243 | 68.6 ± 19.0 | 214 | 66.8 ± 18.1 | 29 | 82.0 ± 20.8 | <0.001 |
| Waist circumference (cm) | 243 | 85.0 ± 17.7 | 214 | 83.5 ± 17.5 | 29 | 95.7 ± 15.8 | <0.001 |
| Waist to Hip ratio health risk (sex-specific)‡ | 0.01 | ||||||
| Low | 89 | 36.6% | 73 | 34.1% | 16 | 55.2% | |
| Moderate | 62 | 25.0% | 53 | 24.8% | 9 | 31.0% | |
| High | 92 | 37.9% | 88 | 41.1% | 4 | 13.8% | |
| BMI category: | 0.04 | ||||||
| Underweight (<18 kg/m2) | 19 | 7.8% | 18 | 8.4% | 1 | 3.5% | |
| Normal (18–24 kg/m2) | 113 | 46.5% | 102 | 47.7% | 11 | 37.9% | |
| Overweight (25–30 kg/m2) | 49 | 20.2% | 37 | 17.3% | 12 | 41.4% | |
| Obese (>30 kg/m2) | 62 | 25.5% | 57 | 26.6% | 5 | 17.2% | |
| BMI (kg/m2) | 243 | 25.6 ± 6.9 | 214 | 25.4 ± 7.0 | 29 | 26.3 ± 5.9 | 0.21 |
| Inflammatory markers: | |||||||
| C-reactive protein (CRP) (mg/dL) | 243 | 0.7 ± 1.2 | 214 | 0.7 ± 1.3 | 29 | 0.6 ± 0.7 | 0.45 |
| C-reactive protein elevated (>0.8 mg/dL) | 51 | 21.0% | 44 | 20.6% | 7 | 24.1% | 0.66 |
| Erythrocyte sedimentation rate (mm/hr) | 243 | 14.4 ± 14.9 | 214 | 15.3 ± 15.2 | 29 | 7.4 ± 10.3 | <0.001 |
| ESR elevated (ESR > 20.0 mm/hr) | 51 | 21.0% | 49 | 22.9% | 2 | 6.9% | 0.05 |
| Psychological function inventories: | |||||||
| State Anxiety inventory average score | 243 | 45.2 ± 13.5 | 214 | 44.9 ± 13.1 | 29 | 47.7 ± 16.3 | 0.46 |
| State Anxiety inventory score ≥ 50 (severe) | 88 | 36.2% | 77 | 36.0% | 11 | 37.9% | |
| Trait Anxiety inventory average score | 243 | 43.9 ± 12.1 | 214 | 43.8 ± 12.1 | 29 | 45.0 ± 12.3 | 0.53 |
| Trait Anxiety inventory score ≥ 50 (severe) | 84 | 34.6% | 71 | 33.2% | 13 | 44.8% | |
| Beck Depression Inventory average score | 243 | 18.6 ± 10.8 | 214 | 18.5 ± 10.7 | 29 | 19.3 ± 11.2 | 0.71 |
| Beck Depression Inv score > 28 (severe) | 44 | 18.1% | 36 | 16.8% | 8 | 27.6% | 0.16 |
| Medical history: | |||||||
| Co-morbidities: | |||||||
| Average number of co-morbidities | 243 | 3.63 ± 2.69 | 214 | 3.68 ± 2.64 | 29 | 3.28 ± 3.10 | 0.22 |
| Migraine Headache (yes vs no) | 99 | 40.7% | 92 | 43.0% | 7 | 24.1% | 0.05 |
| Chronic fatigue syndrome (yes vs no) | 22 | 9.1% | 22 | 10.3% | 0 | 0.0% | 0.09 |
| Fibromyalgia (yes vs no) | 31 | 12.8% | 30 | 14.0% | 1 | 3.5% | 0.14 |
| Major depression (yes vs no) | 53 | 21.8% | 46 | 21.5% | 7 | 24.1% | 0.75 |
| Severe anxiety (yes vs no) | 30 | 12.4% | 26 | 12.2% | 4 | 13.8% | 0.77 |
| Co-medications: | |||||||
| Gastric acid suppressants (yes vs no) | 185 | 76.1% | 162 | 75.7% | 23 | 79.3% | 0.67 |
| Prokinetics (yes vs no) | 118 | 48.6% | 103 | 48.1% | 15 | 51.7% | 0.72 |
| Anti-emetics (yes vs no) | 174 | 71.6% | 154 | 72.0% | 20 | 69.0% | 0.74 |
| Estrogen, progesterone,OCP’s (yes v no) | 58 | 23.9% | 57 | 26.6% | 1 | 3.5% | 0.006 |
| Narcotic pain medications (yes vs no) | 103 | 42.4% | 92 | 43.0% | 11 | 37.9% | 0.60 |
| Medical marijuana use (yes vs no)‡ | 3 | 1.2% | 2 | 0.9% | 1 | 3.5% | 0.32 |
| Total enteral/parenteral support (yes vs no) | 28 | 11.5% | 25 | 11.7% | 3 | 10.3% | 1.00 |
| Post-menopausal (yes vs no) | 67 | 31.3% | 67 | 31.3% | n/a | ||
| Hysterectomy (yes vs no) | 59 | 27.6% | 59 | 27.6% | n/a | ||
| Age at onset of symptoms (years): | 0.64 | ||||||
| 9 – 20 | 41 | 16.9% | 36 | 16.8% | 5 | 17.2% | |
| 21 – 30 | 59 | 24.3% | 51 | 23.8% | 8 | 27.6% | |
| 31 – 44 | 71 | 29.2% | 66 | 30.8% | 5 | 17.2% | |
| 45 – 60 | 59 | 24.3% | 50 | 23.4% | 9 | 31.0% | |
| 61 + | 13 | 5.4% | 11 | 5.1% | 2 | 6.9% | |
| Average age | 243 | 36.1 ± 14.6 | 214 | 36.1 ± 14.6 | 26 | 36.0 ± 15.2 | 0.82 |
| Duration of symptoms at enrollment (yrs): | 0.20 | ||||||
| 0 – 1 | 93 | 38.3% | 81 | 37.9% | 12 | 41.4% | |
| 2 –4 | 76 | 31.3% | 67 | 31.3% | 9 | 31.0% | |
| 5 – 9 | 45 | 18.5% | 43 | 20.1% | 2 | 6.9% | |
| 10+ | 29 | 11.9% | 23 | 10.8% | 6 | 20.7% | |
| Average duration | 243 | 4.8 ± 6.5 | 214 | 4.8 ± 6.6 | 29 | 5.0 ± 6.1 | 0.83 |
| Initial infectious prodrome: | 45 | 18.6% | 40 | 18.7% | 5 | 17.9% | 0.92 |
| Upper respiratory flu-like illness | 11 | 4.6% | 8 | 3.7% | 3 | 10.7% | |
| Food-poisoning like symptoms | 11 | 4.6% | 9 | 4.2% | 2 | 7.1% | |
| Gastroenteritis | 16 | 6.6% | 16 | 7.5% | 0 | 0.0% | |
| Other | 8 | 3.3% | 8 | 3.7% | 0 | 0.0% | |
| Predominant symptom prompting evaluation: | |||||||
| Nausea vs all others | 83 | 34.2% | 73 | 34.1% | 10 | 34.5% | 0.97 |
| Vomiting vs all others | 47 | 19.3% | 43 | 20.1% | 4 | 13.8% | 0.42 |
| Abdominal pain vs all others | 56 | 23.1% | 51 | 23.8% | 5 | 17.2% | 0.43 |
| Bloating vs all others | 17 | 7.0% | 13 | 6.1% | 4 | 13.8% | 0.13 |
| Gastroesophageal reflux vs all others | 14 | 5.8% | 12 | 5.6% | 2 | 6.9% | 0.67 |
| Type of gastroparesis symptom onset: | 0.86 | ||||||
| Acute start | 122 | 50.2% | 107 | 50.0% | 15 | 51.7% | |
| Insidious start | 121 | 49.8% | 107 | 50.0% | 14 | 48.3% | |
| Nature of gastroparesis symptoms: | 0.91 | ||||||
| Chronic, but stable | 54 | 22.2% | 48 | 22.4% | 6 | 20.7% | |
| Chronic, but worsening | 82 | 33.7% | 73 | 34.1% | 9 | 31.0% | |
| Chronic with periodic exacerbations | 80 | 32.9% | 70 | 32.7% | 10 | 34.5% | |
| Cyclic pattern | 26 | 10.7% | 22 | 10.3% | 4 | 13.8% | |
| Gastroparesis severity: | 0.85 | ||||||
| Mild (grade 1) | 34 | 14.0% | 29 | 13.6% | 5 | 17.2% | |
| Compensated (grade 2) | 137 | 56.4% | 121 | 56.5% | 16 | 55.2% | |
| Gastric failure (grade 3) | 71 | 29.2% | 63 | 29.4% | 8 | 27.6% | |
| Irritable bowel syndrome or IBS‡ | 0.68 | ||||||
| Yes, pending exam/test | 157 | 64.6% | 137 | 64.0% | 20 | 69.0% | |
| No | 86 | 35.4% | 77 | 36.0% | 9 | 31.0% | |
| Gastric emptying (scintigraphy): | |||||||
| Percent gastric retention at 2 hr | 243 | 62.7 ± 16.6 | 214 | 63.1 ± 16.7 | 29 | 59.9 ± 16.0 | 0.38 |
| Percent gastric retention at 4 hr | 242 | 28.1 ± 18.8 | 213 | 28.9 ± 19.4 | 29 | 22.2 ± 13.3 | 0.10 |
| Severity of delayed gastric emptying - 4hr: | 0.14 | ||||||
| Mild (0 – 20%) | 108 | 44.6% | 92 | 43.2% | 16 | 55.2% | |
| Moderate (21% – 35%) | 66 | 27.3% | 58 | 27.2% | 8 | 27.6% | |
| Severe (> 35%) | 68 | 28.1% | 63 | 29.6% | 5 | 17.2% | |
| Severity of Symptoms:‡ | |||||||
| Nausea severity | 243 | 3.5 ± 1.4 | 214 | 3.6 ± 1.3 | 29 | 2.8 ± 1.7 | 0.02 |
| Retching severity | 243 | 1.8 ± 1.8 | 214 | 1.9 ± 1.8 | 29 | 1.5 ± 1.5 | 0.29 |
| Vomiting severity | 243 | 1.9 ± 1.9 | 214 | 2.0 ± 1.9 | 29 | 1.5 ± 2.0 | 0.15 |
| Feeling of stomach fullness severity | 241 | 3.7 ± 1.2 | 213 | 3.8 ± 1.1 | 28 | 3.0 ± 1.3 | <0.001 |
| Inability to finish meal severity | 243 | 3.6 ± 1.4 | 214 | 3.7 ± 1.3 | 29 | 2.8 ± 1.7 | 0.003 |
| Excessively full after meal severity | 243 | 3.7 ± 1.3 | 214 | 3.8 ± 1.2 | 29 | 3.2 ± 1.5 | 0.05 |
| Loss of appetite severity | 243 | 3.1 ± 1.5 | 214 | 3.1 ± 1.5 | 29 | 2.7 ± 1.7 | 0.24 |
| Bloating severity | 243 | 3.3 ± 1.5 | 214 | 3.4 ± 1.5 | 29 | 2.7 ± 1.6 | 0.03 |
| Visibly larger stomach severity | 243 | 2.9 ± 1.8 | 214 | 3.0 ± 1.8 | 29 | 2.0 ± 1.9 | 0.008 |
| Cardinal symptom index (GCSI)‡ | 241 | 3.0 ± 1.0 | 213 | 3.1 ± 1.0 | 28 | 2.5 ± 1.1 | 0.008 |
| Upper abdominal pain | 243 | 3.2 ± 1.7 | 214 | 3.2 ± 1.6 | 29 | 2.7 ± 1.8 | 0.09 |
| Upper abdominal discomfort | 243 | 3.3 ± 1.5 | 214 | 3.4 ± 1.5 | 29 | 3.0 ± 1.6 | 0.30 |
| GERD sub-scale‡ | 243 | 2.0 ± 1.4 | 214 | 2.0 ± 1.4 | 29 | 1.9 ± 1.3 | 0.73 |
| Constipation severity | 243 | 2.4 ± 1.8 | 214 | 2.6 ± 1.8 | 29 | 1.4 ± 1.5 | < 0.001 |
| Diarrhea severity | 243 | 1.9 ± 1.7 | 214 | 1.9 ± 1.7 | 29 | 2.1 ± 1.9 | 0.55 |
Means ± standard deviations or percents (%).
The significance of difference in categorical variables between groups was tested with either a chi-square test or Fisher’s Exact Test for non-ordered categories, the Cochran-Armitage test for trend for ordered categories, or with the Wilcoxon rank sum test for continuous measures. All P values are two-sided.
Definitions:
Ever smoked regularly defined as smoking ≥ 20 packs of cigarettes in a lifetime or ≥ 1 cigarette per day for a year.
Waist to hip ratio cardiovascular disease and diabetes health risk category based on NIDDK guidelines defined as follows: Low risk (≤ 0.95 for males, ≤ 0.80 for females), moderate risk (0.96 to 1.0 for males, 0.81 to 0.85 for females), high risk (≥ 1.0 for males, ≥ 0.85 for females)
Medical marijuana use determined via self-reported use in an “other category” of alternative therapies.
Irritable Bowel Syndrome or IBS diagnosis determined from the Rome III Diagnostic Questionnaire analyzed using an analysis program developed by the Rome Foundation (http://www.romecriteria.org/rome_iii_sas/, accessed 03 February 2010).
Symptom severity from the PAGI-SYM (Patient Assessment of GI Symptoms) questionnaire, scores range from 0–5
- Nausea sub-score = mean of the scores for nausea, retching, and vomiting
- Postprandial fullness/early satiety sub-score = mean of the scores for stomach fullness, inability to finish meal, excessive fullness, and loss of appetite
- Bloating sub-score = mean of the scores for bloating and large stomach
Gastroesophageal (GERD) sub-scale = mean of the scores for daytime heartburn, heartburn lying down, daytime chest discomfort, nighttime chest discomfort, daytime reflux, nighttime reflux, and bitter taste
The predominant symptom prompting evaluation of these patients was nausea in 34%, vomiting in 19%, abdominal pain in 23%, bloating in 7%, and gastroesophageal reflux in 6%. Overall, 22% of patients reported chronic stable symptoms, 34% described their symptoms as chronic and worsening, 33% reported chronic symptoms with periodic exacerbations, while 11% had a cyclic pattern of symptoms. 29% had refractory symptoms and could not maintain nutrition orally (gastric failure). The onset of symptoms of gastroparesis was acute in 50% and 19% of patients reported an infectious prodrome with onset of their gastroparesis symptoms. In these patients with IG, 36% scored severe for anxiety state and 35% scored severe for anxiety trait on the STAI, and 18% scored severe depression on the BDI. Patients averaged 3.6 other comorbidities including migraine headaches in 40%, fibromyalgia in 13%, and chronic fatigue syndrome in 9%.
Gender
Female patients comprised 214 of the 243 (88%) patients with gastroparesis (Table 1). Fewer females were overweight (25–30 kg/m2 BMI) (17% vs 41%, P=0.002) or had ever smoked regularly (30% vs 55%, P=0.008) compared to males. More females than males had migraine headaches (43% vs 24%, P=0.05). Females had an average of 7% higher gastric retention at 4 hours compared to males (28.9±19.4% vs 22.2±13.3%, P=0.10). Females had higher symptom severity scores than male patients for nausea (3.6±1.3 vs 2.8±1.7, P=0.02), stomach fullness (3.8±1.1 vs 3.0±1.3, P<0.001), inability to finish a meal (3.7±1.3 vs 2.8±1.7, P=0.003), excessive fullness after a meal (3.8±1.2 vs 3.2±1.5, P=0.05), bloating (3.4±1.5 vs 2.7±1.6, P=0.03), visible stomach distention (3.0±1.8 vs 2.0±1.9, P=0.008) and constipation (2.6±1.8 vs 1.4±1.5, P<0.001). The GCSI score was higher in females than in males (3.1±1.0 vs 2.5±1.1, P=0.008).
The 12 features associated with females with IG compared to males with IG identified from multiple logistic regression (Table 4) were: drank alcohol in past year (OR=3.49, P=0.04), higher waist to hip ratio category (overall P=0.002), less likely to be overweight or obese (OR=0.14, P=0.002), higher ESR (OR=1.89, P=0.004), more migraine headaches (OR=3.34, P=0.05) and anxiety disorder (7.92, P=0.03), less clinically severe depression (using BDI) (OR=0.20, P=0.01), more severe symptoms at enrollment including nausea (1.69, P=0.02), stomach fullness (OR=1.94, P=0.01), and constipation (OR=1.48, P=0.03), and less severe upper abdominal discomfort (OR=0.55, P=0.02) and diarrhea (OR=0.63, P=0.02). GCSI score was also higher in female compared to male IG patients (OR=1.89, P=0.02).
Table 4.
Multivariable logistic regression analysis to identify independent characteristics of patients with idiopathic gastroparesis that are associated with either sex, overweight, symptom onset, severity of gastric emptying delay, or severity of gastroparesis
| Characteristics Selected | Females Vs Males* |
Overweight Vs Normal* |
Acute Vs Insidious* |
Severe delay Vs Not severe* |
Gastric failure Vs Mild/Comp* |
Severe Symptoms Vs Less* |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR† | P | OR† | P | OR† | P | OR† | P | OR† | P | OR† | P | |
| Demographic and lifestyle: | ||||||||||||
| Sex: Females vs Males | n/a | n/a | 0.11 | <0.001 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Married (yes vs no) | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | 2.12 | 0.03 | n/s | n/s |
| College or higher education (yesVno) | n/s | n/s | 0.21 | <0.001 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Income: $50,000 or more (yes vs no) | n/s | n/s | n/s | n/s | n/s | n/s | 0.42 | 0.01 | n/s | n/s | n/s | n/s |
| Ever drink in past year | 3.49 | 0.04 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Anthropometry: | ||||||||||||
| Waist to hip ratio cardiovascular risk category (sex specific):‡ | 0.002 | 0.01 | 0.004 | 0.02 | n/s | n/s | ||||||
| Low risk | 1.00 | 1.00 | 1.00 | 1.00 | n/s | n/s | n/s | n/s | ||||
| Moderate risk | 2.14 | 0.25 | 1.67 | 0.26 | 4.02 | 0.002 | 1.63 | 0.29 | n/s | n/s | n/s | n/s |
| High risk | 12.20 | 0.002 | 3.40 | 0.004 | 1.48 | 0.28 | 3.19 | 0.006 | n/s | n/s | n/s | n/s |
| Overweight (BMI≥25 kg/m2) | 0.14 | 0.002 | n/a | n/a | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Inflammatory markers: | ||||||||||||
| C-reactive protein (CRP) (√mg/dL) | n/s | n/s | 2.90 | 0.008 | n/s | n/s | 0.42 | 0.03 | n/s | n/s | n/s | n/s |
| ESR (√mm/hr)‡ | 1.89 | 0.004 | 1.69 | <0.001 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Medical history: | ||||||||||||
| Co-morbidities: | ||||||||||||
| Migraine headache (yes vs no) | 3.34 | 0.05 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | 2.33 | 0.003 |
| Fibromyalgia (yes vs no) | n/a | n/a | n/s | n/s | 0.22 | 0.005 | 6.97 | <0.001 | n/s | n/s | 0.29 | 0.01 |
| Major depression (yes vs no) | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | 2.12 | 0.03 |
| Anxiety disorder (yes vs no) | 7.92 | 0.03 | 4.09 | 0.01 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Beck Depression Index score > 30‡ | 0.20 | 0.01 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s |
| Co-medications: | ||||||||||||
| Gastric acid suppressants | n/s | n/s | n/s | n/s | n/s | n/s | 2.65 | 0.03 | n/s | n/s | n/s | n/s |
| Prokinetics | n/s | n/s | n/s | n/s | 0.41 | 0.008 | n/s | n/s | n/s | n/s | n/s | n/s |
| Anti-emetics | n/s | n/s | n/s | n/s | 3.56 | 0.001 | 5.76 | <0.001 | 4.06 | 0.004 | n/s | n/s |
| Estrogen, progesterone, OCP’s | n/a | n/a | n/s | n/s | 0.43 | 0.03 | n/s | n/s | n/s | n/s | n/s | n/s |
| Total enteral/parenteral support (yes) | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | 6.41 | <0.001 | n/s | n/s |
| Post-menopausal (yes vs no) | n/a | n/a | n/s | n/s | n/s | n/s | n/s | n/s | 0.30 | 0.004 | n/s | n/s |
| Duration of symptoms at enrollment : | n/s | n/s | < 0.001 | n/s | n/s | n/s | ||||||
| 0 – 1.5 years | n/s | n/s | 1.00 | n/s | n/s | n/s | ||||||
| 1.6 – 4 years | n/s | n/s | n/s | n/s | 0.27 | 0.001 | n/s | n/s | n/s | n/s | n/s | n/s |
| 5+ years | n/s | n/s | n/s | n/s | 0.20 | <0.001 | n/s | n/s | n/s | n/s | n/s | n/s |
| Initial infectious prodrome (yesVno) | n/s | n/s | n/s | n/s | 4.43 | 0.001 | 0.30 | 0.02 | n/s | n/s | n/s | n/s |
| Gastric emptying (scintigraphy): | ||||||||||||
| Percent gastric retention at 2 hr | n/s | n/s | 1.03 | 0.004 | n/s | n/s | n/a | n/a | n/s | n/s | n/s | n/s |
| Percent gastric retention at 4 hr | n/s | n/s | n/s | n/s | n/s | n/s | n/a | n/a | n/s | n/s | 1.02 | 0.01 |
| Severity of symptoms:‡ | ||||||||||||
| Nausea severity | 1.69 | 0.02 | n/s | n/s | 1.37 | 0.01 | n/s | n/s | 1.45 | 0.006 | n/a | n/a |
| Vomiting severity | n/s | n/s | n/s | n/s | n/s | n/s | 1.25 | 0.02 | n/s | n/s | n/a | n/a |
| Feeling of stomach fullness severity | 1.94 | 0.01 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/a | n/a |
| Loss of appetite severity | n/s | n/s | 0.63 | <0.001 | n/s | n/s | 1.38 | 0.01 | n/s | n/s | n/a | n/a |
| Bloating severity | n/s | n/s | 1.34 | 0.03 | n/s | n/s | n/s | n/s | n/s | n/s | n/a | n/a |
| Upper abdominal discomfort | 0.55 | 0.02 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | ||
| Lower abdominal pain severity | n/s | n/s | 0.48 | 0.009 | 0.45 | 0.002 | n/s | n/s | n/s | n/s | ||
| Lower abdominal discomfort severity | n/s | n/s | 1.79 | 0.03 | 1.62 | 0.05 | n/s | n/s | n/s | n/s | ||
| Constipation severity | 1.48 | 0.03 | n/s | n/s | 0.80 | 0.02 | n/s | n/s | n/s | n/s | ||
| Diarrhea severity | 0.63 | 0.02 | n/s | n/s | n/s | n/s | n/s | n/s | n/s | n/s | ||
| Cardinal Symptom Index (GCSI)‡ | 1.89 | 0.02§ | n/s | n/s | n/s | n/s | 1.42 | 0.05§ | 1.49 | 0.02§ | n/a | n/a |
Females (N=213), Males (N=28)
Overweight defined as Body Mass Index (BMI) ≥ 25 kg/m2 (N=111), Normal or less defined as BMI < 25 kg/m2 (N=132)
Acute onset of symptoms (N=122), Insidious onset (N=120)
Severe delay in gastric emptying at 4-hours is % retention > 35% (N=68), Not severe delay (N=173)
Severe gastroparesis defined as Grade 3: gastric failure (N=72), Grade 1: mild and Grade 2: compensated gastroparesis (N=171) using the gastroparesis severity scale reported in the ANMS review on treatment of gastroparesis (4).
Severity of symptoms based on the GCSI score from the PAGI-SYM questionnaire: Severe symptoms defined as GCSI ≥ 3.5 (N=90), Less severe symptoms defined as GCSI < 3.5 (N=150)
Independent characteristics and associated odds ratios were determined from bi-directional multivariable logistic regression analysis for each sub-group (sex, body mass, symptom onset, severity of delayed gastric empting, gastroparesis severity) using the full candidate set of characteristics shown in Tables 1–4, 6–7
n/a = Characteristic not in model due to instability of model due to multicollinearity.
n/s = Characteristic not significant at the 0.05 level
Definitions:
- Low risk (≤ 0.95 for males, ≤ 0.80 for females), moderate risk (0.96 to 1.0 for males, 0.81 to 0.85 for females, high risk (≥ 1.0 for males, ≥ for females)
ESR = Erythrocyte sedimentation rate
Beck Depression Index > 30 indicates clinically severe depression
Symptom severity from the PAGI-SYM (Patient Assessment of GI Symptoms) questionnaire, scores range from 0–5
- Nausea sub-score = mean of the scores for nausea, retching, and vomiting
-
Postprandial fullness/early satiety sub-score = mean of the scores for stomach fullness, inability to finish meal, excessive fullness, and loss of appetite
- Bloating sub-score = mean of the scores for bloating and large stomach
Odds ratios and P values determined from a separate model including GCSI instead of the 9 separate symptom severity scores.
Body mass
Of 243 patients with idiopathic gastroparesis, 132 (54%) were either normal weight or underweight whereas 111 (46%) were overweight or obese, which for further analysis, were pooled and labeled overweight (Supplemental Table 2). Overweight (BMI≥25 kg/m2) IG patients were older at symptom onset (38.1±14.4 vs 34.5±14.7 years, P=0.05) and were less educated (20% vs 44% college or more, P<0.001) than those who were not overweight (BMI<25 kg/m2). Overweight patients had similar type of symptom onset compared to normal weight individuals (52% vs 48% acute onset, P=0.40). An infectious-like prodrome was present in only 11% of overweight patients compared to 25% of normal weight patients (P=0.005). Increased gastric retention at 2 hours was more likely in overweight compared to normal weight patients (67±17% vs 60±16% retention, P=0.001), but gastric emptying was not significantly different at 4 hours (31±21 vs 26±17%, P=0.19). Patients who were overweight had elevated inflammatory markers compared to normal weight patients (ESR: 19±16 vs 10±13 mm/hr, P<0.001; and CRP: 0.9±1.2 vs 0.5±1.2, P<0.001). Overweight patients reported less severe loss of appetite (2.7±1.5 vs 3.4±1.4, P<0.001), had a lower score for inability to finish a meal (3.4±1.4 vs 3.8±1.4, P=0.02) and had higher gastroesophageal reflux scores (2.2±1.4 vs 1.9±1.4, P=0.06) compared to normal weight patients.
Multiple logistic regression resulted in 11 features associated with overweight (BMI≥25 kg/m2) versus normal weight (BMI<25 kg/m2) IG patients: less likely to be females (OR=0.11, P<0.001), lower income (OR=0.21 $50K+, P<0.001), higher waist to hip ratio category (overall P=0.01), higher ESR (OR=1.69, P<0.001), higher CRP (OR=2.90, P=0.008), increased anxiety disorder (4.09, P=0.01), higher percent gastric retention at 2 hours (OR=1.03, P=0.004), increased severity of bloating (1.34, P=0.03) and lower abdominal discomfort (OR=1.79, P=0.03) and less severe appetite loss (OR=0.63, P<0.001) and lower abdominal pain (OR=0.48, p=0.009) (Table 4).
Symptom Onset
Of the 122 patients who presented with acute symptoms at onset (Supplemental Table 3), 27.1% reported an infectious etiology compared to 10% of IG patients with an insidious symptom onset (P<0.001). The average score on the BDI was lower in patients with acute symptom onset compared to those with insidious onset (17±10 vs 20±12, P=0.03), and there was less reported fibromyalgia (6% vs 20%, P=0.001) in the acute onset group. Acute onset patients reported taking more anti-emetic medications than the insidious onset group (80% vs 63%, P=0.003). Patients with acute onset had a shorter duration of symptoms (3.5±4.4 vs 6.1±7.9 years, P<0.001), and tended to have more gastric failure (34% vs 24%, P=0.07) compared to those with insidious onset. Patients with acute onset reported less severe lower abdominal pain (1.8±1.6 vs 2.5±1.7, P=0.001), lower abdominal discomfort (2.0±1.7 vs 2.6±1.6, P=0.01), and constipation (2.2±1.9 vs 2.7±1.8, P=0.02) than patients with insidious onset.
Eleven features were associated with IG patients with acute onset compared to insidious onset of symptoms by multiple logistic regression analyses (Table 4). These were: higher waist to hip ratio category (overall P=0.004; moderate risk category vs low risk OR=4.02, P=0.002), less fibromyalgia (OR=0.22, P=0.005), less likely to use prokinetics (OR=0.41, P=0.008) and less likely to use estrogen/progesterone (OR=0.43, P=0.03), more likely to use anti-emetics (OR=3.56, P=0.001), shorter duration of symptoms (overall P<0.001), an initial infectious prodrome (OR=4.43, P=0.001), more severe nausea (OR=1.37, P=0.01) and lower abdominal discomfort (OR=1.62, P=0.05), and less severe lower abdominal pain (OR=0.45, P=0.002) and constipation (OR=0.80, P=0.02).
Gastric emptying
Overall, of 242 IG patients with gastric emptying scintigraphy results at 4 hours, delayed gastric emptying was mild (≤20% gastric retention) in 45%, moderate (>20 to 35%) in 27%, and severe (>35%) in 28% (Table 2). Patients with severe gastric retention had the lowest percent of incomes > $50K (41% vs 56% vs 69%, P<0.001), and reported more co-morbidities: Chronic fatigue syndrome (16% vs 9% vs 5%, P=0.01), fibromyalgia (24% vs 17% vs 4%, P<0.001), major depression (34% vs 20% vs 16%, P=0.006). Patients with severe gastric retention also reported more use of co-medications: anti-emetics (90% vs 58% vs 69%, P<0.001), gastric acid suppressants (85% vs 76% vs 71%, P=0.04), narcotics (57% vs 44% vs 32%, P=0.001). Patients with more severe retention had the longest duration of symptoms (5.9±7.6 vs 4.7±7.1 vs 4.2±5.2 years, P=0.09), and reported an initial infectious prodrome less frequently (10% vs 19% vs 24%, P=0.02). Patients with severe gastric emptying were more likely to be classified as having gastric failure (35%) compared to 26% with mild and moderate delay (P=0.06) Patients with severe retention reported more severe nausea (3.8±1.2 vs 3.4±1.3 vs 3.3±1.6, P=0.05), vomiting (2.5±1.9 vs 1.7±1.9 vs 1.8±1.9, P=0.01), retching (2.3±1.9 vs 1.5±1.6 vs 1.7±1.7, P=0.02), loss of appetite (3.4±1.4 vs 3.2±1.4 vs 2.8±1.6, P=0.04), upper abdominal discomfort (3.7±1.4 vs 3.4±1.3 vs 3.1±1.6, P=0.05), gastroesophageal reflux scores (2.5±1.4 vs 1.8±1.3 vs 1.9±1.4, P=0.007), and had higher GCSI scores (3.3±1.0 vs 2.9±0.8 vs 2.9±1.1, P=0.04) compared to patients with moderate or mild retention, respectively.
Table 2.
Characteristics of patients with idiopathic gastroparesis with mild, moderate, or severe delay in 4-hour gastric emptying
| Severity of delay in gastric emptying at 4 hours* | |||||||
|---|---|---|---|---|---|---|---|
| Mild (N = 108) |
Moderate (N = 66) |
Severe (N = 68) |
P value‡ |
||||
| Characteristic | No. | Statistic† | No. | Statistic† | No. | Statistic† | |
| Demographic and lifestyle: | |||||||
| Age at enrollment (yrs) | 108 | 39.9 ± 14.1 | 66 | 42.9 ± 14.8 | 68 | 41.0 ± 13.2 | 0.38 |
| Gender: Females | 92 | 85.2% | 58 | 87.9% | 63 | 92.7% | 0.15 |
| Married: (yes vs no) | 67 | 62.0% | 38 | 57.6% | 38 | 55.9% | 0.40 |
| College degree or higher (yes vs no) | 37 | 34.3% | 23 | 34.9% | 19 | 27.9% | 0.42 |
| Income $50,000+ (yes vs no) | 74 | 68.5% | 37 | 56.1% | 28 | 41.2% | <0.001 |
| Ever smoked regularly (yes vs no)§ | 36 | 33.3% | 20 | 30.3% | 24 | 35.3% | 0.83 |
| Ever drink (past year) | 49 | 45.4% | 25 | 37.9% | 21 | 30.1% | 0.45 |
| Anthropometry: | |||||||
| Waist circumference (cm) | 108 | 83.7 ± 16.8 | 66 | 82.9 ± 18.4 | 68 | 88.6 ± 8.0 | 0.08 |
| Waist to hip ratio | 108 | 0.85 ± 0.09 | 66 | 0.84 ± 0.15 | 68 | 0.86 ± 0.08 | 0.04 |
| Overweight: (yes vs no)§ | 44 | 40.7% | 32 | 48.5% | 34 | 50.0% | 0.21 |
| BMI (kg/m2) | 108 | 25.3 ± 6.8 | 66 | 24.5 ± 5.4 | 68 | 26.8 ± 8.0 | 0.37 |
| Inflammatory markers: | |||||||
| C-reactive protein (CRP) (mg/dL) | 108 | 0.7 ± 1.4 | 66 | 0.6 ± 1.2 | 68 | 0.7 ± 1.0 | 0.65 |
| CRP elevated (> 0.8 mg/dL) | 23 | 21.3% | 10 | 15.2% | 18 | 26.5% | 0.52 |
| ESR rate (mm/hr)§ | 108 | 13.4 ± 13.3 | 66 | 13.1 ± 12.4 | 68 | 17.0 ± 19.0 | 0.49 |
| ESR elevated (> 20 mm/hr)§ | 23 | 21.3% | 11 | 16.7% | 16 | 23.5% | 0.60 |
| Psychological function inventories: | |||||||
| State Anxiety inventory average score | 108 | 44.3 ± 13.9 | 66 | 44.1 ± 13.9 | 68 | 47.6 ± 12.4 | 0.21 |
| State Anxiety inventory score ≥ 50 | 38 | 35.2% | 21 | 31.8% | 28 | 41.2% | 0.09 |
| Trait Anxiety inventory average score | 108 | 43.0 ± 12.8 | 66 | 43.3 ± 11.8 | 68 | 45.9 ± 8.0 | 0.20 |
| Trait Anxiety inventory score ≥ 50 | 35 | 32.4% | 23 | 34.9% | 26 | 38.2% | 0.24 |
| Beck Depression Inventory avg score | 108 | 18.1 ± 10.6 | 66 | 17.1 ± 9.6 | 68 | 20.9 ± 11.9 | 0.18 |
| Beck Depression inventory > 28 | 18 | 16.7% | 8 | 12.1% | 18 | 26.5% | 0.08 |
| Medical history: | |||||||
| Co-morbidities: | |||||||
| Average number of co-morbidities | 108 | 3.13 ± 2.01 | 66 | 3.35 ± 2.80 | 68 | 4.72 ± 3.23 | 0.002 |
| Migraine Headache (yes vs no) | 43 | 39.8% | 25 | 37.9% | 31 | 45.6% | 0.63 |
| Chronic fatigue syndrome (yes vs no) | 5 | 4.6% | 6 | 9.1% | 11 | 16.2% | 0.01 |
| Fibromyalgia (yes vs no) | 4 | 3.7% | 11 | 16.7% | 16 | 23.5% | < 0.001 |
| Major depression (yes vs no) | 17 | 15.7% | 13 | 19.7% | 23 | 33.8% | 0.006 |
| Severe anxiety (yes vs no) | 12 | 11.1% | 5 | 7.6% | 13 | 19.1% | 0.13 |
| Co-medications: | |||||||
| Gastric acid suppressants (yes vs no) | 77 | 71.3% | 50 | 75.8% | 58 | 85.3% | 0.04 |
| Prokinetics (yes vs no) | 48 | 44.4% | 31 | 47.0% | 38 | 55.9% | 0.15 |
| Anti-emetics (yes vs no) | 74 | 68.5% | 38 | 57.6% | 61 | 89.7% | < 0.001 |
| Estrogen, progesterone,OCP’s (yes) | 28 | 25.9% | 14 | 21.2% | 16 | 23.5% | 0.78 |
| Narcotic pain medications (yes vs no) | 35 | 32.4% | 29 | 43.9% | 39 | 57.4% | 0.001 |
| Total enteral/parenteral support (yes/no) | 11 | 10.2% | 4 | 6.1% | 13 | 19.1% | 0.05 |
| Post-menopausal (yes vs no) | 28 | 30.4% | 22 | 37.9% | 17 | 27.0% | 0.42 |
| Age at symptom onset (years) | 108 | 35.7 ± 14.5 | 66 | 38.2 ± 15.4 | 68 | 35.1 ± 14.2 | 0.42 |
| Duration of symptoms at enrollment(yrs) | 108 | 4.2 ± 5.2 | 66 | 4.7 ± 7.1 | 68 | 5.9 ± 7.6 | 0.09 |
| Initial infectious prodrome: (yes vs no) | 26 | 24.1% | 12 | 18.5% | 7 | 10.3% | 0.02 |
| Predominant symptom: | |||||||
| Nausea vs all others | 38 | 35.2% | 20 | 30.3% | 24 | 35.3% | 0.77 |
| Vomiting vs all others | 17 | 15.7% | 16 | 24.2% | 14 | 20.6% | 0.37 |
| Abdominal pain vs all others | 25 | 23.2% | 13 | 19.7% | 18 | 26.5% | 0.68 |
| Type of gastroparesis symptom onset: | 0.37 | ||||||
| Acute start | 57 | 52.8% | 34 | 51.5% | 31 | 45.6% | |
| Insidious start | 51 | 47.2% | 32 | 48.5% | 37 | 54.4% | |
| Nature of gastroparesis symptoms: | 0.24 | ||||||
| Chronic, but stable | 21 | 19.4% | 21 | 31.8% | 12 | 17.7% | |
| Chronic, but progressively worse | 35 | 32.4% | 19 | 28.8% | 28 | 41.2% | |
| Chronic with periodic exacerbations | 38 | 35.2% | 22 | 33.3% | 19 | 27.9% | |
| Cyclic pattern | 13 | 12.0% | 4 | 6.1% | 9 | 13.2% | |
| Gastroparesis severity: | 0.17 | ||||||
| Mild (grade 1) | 13 | 12.0% | 11 | 16.7% | 10 | 14.7% | |
| Compensated (grade 2) | 61 | 56.5% | 43 | 65.2% | 33 | 48.5% | |
| Gastric failure (grade 3) | 34 | 31.5% | 12 | 18.2% | 24 | 35.3% | |
| Gastric failure vs less severe | 34 | 31.5% | 12 | 18.2% | 24 | 35.3% | 0.06 |
| Irritable bowel syndrome or IBS§ | 0.04 | ||||||
| Yes, pending exam/test | 63 | 58.3% | 44 | 66.7% | 50 | 73.5% | |
| No | 45 | 41.7% | 22 | 33.3% | 18 | 26.5% | |
| Gastric emptying (scintigraphy): | |||||||
| Percent gastric retention at 4 hr. | 108 | 13.3 ± 4.7 | 66 | 26.2 ± 4.1 | 68 | 53.5 ± 14.5 | < 0.001 |
| Severity of symptoms:§ | |||||||
| Nausea severity | 108 | 3.3 ± 1.6 | 68 | 3.4 ± 1.3 | 68 | 3.8 ± 1.2 | 0.05 |
| Retching severity | 108 | 1.7 ± 1.7 | 66 | 1.5 ± 1.6 | 68 | 2.3 ± 1.9 | 0.02 |
| Vomiting severity | 108 | 1.8 ± 1.9 | 66 | 1.7 ± 1.9 | 68 | 2.5 ± 1.9 | 0.01 |
| Stomach fullness severity | 106 | 3.7 ± 1.2 | 66 | 3.7 ± 1.1 | 68 | 3.8 ± 1.2 | 0.51 |
| Inability to finish meal severity | 108 | 3.4 ± 1.5 | 66 | 3.6 ± 1.3 | 68 | 3.8 ± 1.2 | 0.41 |
| Excessively full post meal severity | 108 | 3.6 ± 1.3 | 66 | 3.7 ± 1.3 | 68 | 3.9 ± 1.1 | 0.59 |
| Loss of appetite severity | 108 | 2.8 ± 1.6 | 66 | 3.2 ± 1.4 | 68 | 3.4 ± 1.4 | 0.04 |
| Bloating severity | 108 | 3.2 ± 1.7 | 66 | 3.3 ± 1.4 | 68 | 3.4 ± 1.4 | 0.71 |
| Visibly larger stomach severity | 108 | 2.8 ± 1.9 | 66 | 2.9 ± 1.8 | 68 | 3.0 ± 1.7 | 0.75 |
| Cardinal symptom index (GCSI)§ | 106 | 2.9 ± 1.1 | 66 | 2.9 ± 0.8 | 68 | 3.3 ± 1.0 | 0.04 |
| Upper abdominal pain | 108 | 2.9 ± 1.8 | 66 | 3.1 ± 1.5 | 68 | 3.5 ± 1.6 | 0.12 |
| Upper abdominal discomfort | 108 | 3.1 ± 1.6 | 66 | 3.4 ± 1.3 | 68 | 3.7 ± 1.4 | 0.05 |
| Lower abdominal pain | 108 | 2.0 ± 1.8 | 66 | 2.2 ± 1.4 | 68 | 2.5 ± 1.8 | 0.20 |
| Lower abdominal discomfort | 108 | 2.1 ± 1.7 | 66 | 2.4 ± 1.5 | 68 | 2.6 ± 1.8 | 0.18 |
| GERD sub-scale | 108 | 1.9 ± 1.4 | 66 | 1.8 ± 1.3 | 68 | 2.5 ± 1.4 | 0.007 |
| Constipation severity | 108 | 2.2 ± 1.8 | 66 | 2.7 ± 1.6 | 68 | 2.7 ± 1.9 | 0.10 |
| Diarrhea severity | 108 | 2.0 ± 1.7 | 66 | 1.6 ± 1.6 | 68 | 2.0 ± 1.8 | 0.21 |
Percent gastric retention at 4-hours: Mild= 20% or less, Moderate= 21% to 35%, Severe= >35%.
Means ± standard deviations or percents (%).
The significance of difference in categorical variables between groups was tested with either a chi-square test or Fisher’s Exact Test for non-ordered categories, the Cochran-Armitage test for trend for ordered categories, or with the Wilcoxon rank sum test for continuous measures. All P values are two-sided.
Definitions:
Ever smoked regularly defined as smoking ≥ 20 packs of cigarettes in a lifetime or ≥ 1 cigarette per day for a year.
Overweight = BMI ≥ 25 kg/m2
ESR = Erythrocyte sedimentation rate
Irritable Bowel Syndrome or IBS diagnosis determined from the Rome III Diagnostic Questionnaire analyzed using an analysis program developed by the Rome Foundation (http://www.romecriteria.org/rome_iii_sas/, accessed 03 February 2010).
Symptom severity from the PAGI-SYM (Patient Assessment of GI Symptoms) questionnaire, scores range from 0–5
Gastroparesis cardinal symptom index (GCSI) = mean of the sub-scores for nausea, postprandial fullness, and bloating.
Multivariable logistic regression comparing severe to not severe (mild plus moderate) gastric retention at 4 hours identified the following 9 features associated with severe retention (Table 4): lower income (OR=0.42, P=0.01), higher waist to hip ratio CVD risk category (overall P=0.02; high risk OR=3.19, P=0.006 vs low risk category), lower CRP (OR=0.42, P=0.03), more likely to have fibromyalgia (OR=6.97, P<0.001), use anti-emetics (OR=5.76, P<0.001), use gastric acid suppressants (OR=2.65, P=0.03) and less likely to have an initial infectious prodrome (OR=0.30, P=0.02). Patients with severe gastric retention had more severe vomiting (OR=1.25, P=0.02) and loss of appetite (OR=1.38, P=0.01). The GCSI score was significantly higher in patients with severe compared to less severe retention (OR=1.42, P=0.05).
Gastroparesis Symptom Severity
The severity of gastroparesis was also assessed using the gastroparesis severity scale (4) with gastroparesis severity graded as grade 1: mild gastroparesis, grade 2: compensated gastroparesis, and grade 3: severe gastroparesis with gastric failure (Supplemental Table 4). With increasing severity of gastroparesis, there were significantly increased symptoms of nausea, retching, vomiting, bloating, upper abdominal pain/discomfort, and symptoms of GERD. The GCSI score increased with increasing severity of gastroparesis (2.4±0.9 vs 3.0±1.1 vs 3.3±0.8, P<0.001). The retention at 2 and 4 hours was not significantly different among the different grades. There was an increase in the inflammatory markers CRP and ESR with increasing severity of gastroparesis. In addition, there were increased STAI and BDI scores. With increasing severity of gastroparesis, there were increased use of anti-emetics, narcotic pain medications, and nutritional support using TPN or jejunostomy tube. Multivariable logistic regression was used to identify independent characteristics of patients with IG that were associated with gastric failure compared to mild or compensated gastroparesis (Table 4). Use of antiemetic agents (OR=4.06; P=0.004), use of total/parenteral support (OR=6.41; P<0.001), nausea severity score (OR=1.45; P=0.006), and being married (OR=2.12; P=0.03) were associated with severe gastroparesis, whereas being postmenopausal was associated with mild/compensated gastroparesis (OR=0.30; P=0.004). In addition, the GCSI score was associated with severe gastroparesis (OR=1.49; P=0.02).
Symptom severity of gastroparesis was also assessed by dividing patients according to their GCSI score: mild or less (0–2.99), moderate (3.0–3.99), and severe (4.0–5.0) (Table 3). With increasing symptom severity, there was an increase in gastroparesis severity (P=0.004) and increased predominant symptom of nausea for gastroparesis evaluation. Percent gastric retention at 4 hours increased with increasing symptom severity (26±18% vs 27±18% vs 36±23%, P=0.06) and there was an increase in number of patients with severe delay in gastric emptying (P=0.03). Independent characteristics associated with severe symptom severity (GCSI≥3.5) compared to mild to moderate symptoms (GCSI<3.5) included more percent retention at 4 hours (OR=1.02; p=0.01), migraine headaches (OR=2.33; p=0.003), major depression disorder (OR=2.12; p=0.03), and less fibromyalgia (OR=0.29; p=0.01) (Table 4).
Table 3.
Characteristics of patients with idiopathic gastroparesis with mild, moderate or severe symptoms based on the Gastroparesis Cardinal Symptom Index
| Severity of symptoms by GCSI* | |||||||
|---|---|---|---|---|---|---|---|
| Mild GCSI: 0 – 2.99 (N = 114) |
Moderate GCSI: 3.0 – 3.99 (N = 86) |
Severe GCSI:4.0 – 5.0 (N = 41) |
P value‡ |
||||
| Characteristic | No. | Statistic† | No. | Statistic† | No. | Statistic† | |
| Demographic and lifestyle: | |||||||
| Age at enrollment (yrs) | 114 | 41.6 ± 16.0 | 86 | 41.3 ± 12.2 | 41 | 39.2 ± 12.1 | 0.68 |
| Gender: Females | 95 | 83.3% | 78 | 90.7% | 40 | 97.6% | 0.01 |
| Married: (yes vs no) | 63 | 55.3% | 54 | 62.8% | 25 | 61.0% | 0.38 |
| College degree or higher (yes vs no) | 43 | 37.7% | 25 | 29.1% | 12 | 29.3% | 0.21 |
| Income $50,000+ (yes vs no) | 72 | 63.2% | 40 | 46.5% | 26 | 63.4% | 0.46 |
| Ever smoked regularly (yes vs no)§ | 33 | 29.0% | 37 | 43.0% | 10 | 24.4% | 0.82 |
| Ever drink (past year) | 53 | 46.5% | 28 | 32.6% | 14 | 34.2% | 0.07 |
| Anthropometry: | |||||||
| Waist circumference (cm) | 114 | 85.3 ± 18.3 | 86 | 85.1 ± 18.0 | 41 | 84.3 ± 16.0 | 0.98 |
| Waist to hip ratio | 114 | 0.85 ± 0.09 | 86 | 0.86 ± 0.13 | 41 | 0.84 ± 0.08 | 0.89 |
| Overweight: (yes vs no)§ | 54 | 47.4% | 39 | 45.4% | 17 | 41.5% | 0.52 |
| BMI (kg/m2) | 114 | 25.7 ± 7.6 | 86 | 25.2 ± 6.1 | 41 | 25.8 ± 6.8 | 0.96 |
| Inflammatory markers: | |||||||
| C-reactive protein (CRP) (mg/dL) | 114 | 0.7 ± 1.5 | 86 | 0.5 ± 0.6 | 41 | 1.0 ± 1.2 | 0.02 |
| CRP elevated (> 0.8 mg/dL) | 21 | 18.4% | 14 | 16.3% | 16 | 39.0% | 0.03 |
| ESR rate (mm/hr)§ | 114 | 13.4 ± 16.5 | 86 | 15.4 ± 13.4 | 41 | 14.8 ± 13.5 | 0.06 |
| ESR elevated (> 20 mm/hr)§ | 20 | 17.5% | 20 | 23.3% | 10 | 24.4% | 0.27 |
| Psychological function inventories: | |||||||
| State Anxiety inventory average score | 114 | 42.8 ± 12.6 | 86 | 48.3 ± 14.2 | 41 | 45.8 ± 13.3 | 0.03 |
| State Anxiety inventory score ≥ 50 | 36 | 31.6% | 37 | 43.0% | 15 | 36.6% | 0.31 |
| Trait Anxiety inventory average score | 114 | 42.5 ± 12.0 | 86 | 46.2 ± 12.2 | 41 | 43.5 ± 11.7 | 0.12 |
| Trait Anxiety inventory score ≥ 50 | 25 | 30.7% | 35 | 40.7% | 14 | 34.2% | 0.42 |
| Beck Depression Inventory avg score | 114 | 15.5 ± 9.6 | 86 | 21.7 ± 11.0 | 41 | 21.0 ± 11.2 | < 0.001 |
| Beck Depression inventory > 28 | 13 | 11.4% | 22 | 25.6% | 9 | 22.0% | 0.04 |
| Medical history: | |||||||
| Co-morbidities: | |||||||
| Averag number of co-morbidities | 114 | 3.29 ± 2.64 | 86 | 3.76 ± 2.45 | 41 | 4.32 ± 3.24 | 0.06 |
| Migraine Headache (yes vs no) | 36 | 31.6% | 37 | 43.0% | 24 | 58.5% | 0.002 |
| Chronic fatigue syndrome (yes vs no) | 8 | 7.0% | 10 | 11.6% | 4 | 9.8% | 0.42 |
| Fibromyalgia (yes vs no) | 16 | 14.0% | 10 | 11.6% | 5 | 12.2% | 0.68 |
| Major depression (yes vs no) | 17 | 14.9% | 25 | 29.1% | 11 | 26.8% | 0.04 |
| Severe anxiety (yes vs no) | 14 | 12.3% | 10 | 11.6% | 6 | 14.6% | 0.78 |
| Co-medications: | |||||||
| Gastric acid suppressants (yes vs no) | 86 | 75.4% | 64 | 74.4% | 34 | 82.9% | 0.45 |
| Prokinetics (yes vs no) | 45 | 48.3% | 45 | 52.3% | 18 | 43.9% | 0.83 |
| Anti-emetics (yes vs no) | 79 | 69.3% | 58 | 67.4% | 35 | 85.4% | 0.12 |
| Estrogen, progesterone,OCP’s (yes) | 30 | 26.3% | 19 | 22.1% | 9 | 22.0% | 0.40 |
| Narcotic pain medications (yes vs no) | 43 | 37.7% | 36 | 41.9% | 23 | 56.1% | 0.06 |
| Total enteral/parenteral support (yes/no) | 9 | 7.9% | 9 | 10.5% | 9 | 22.0% | 0.02 |
| Post-menopausal (yes vs no) | 29 | 30.5% | 26 | 33.3% | 12 | 30.0% | 0.95 |
| Age at symptom onset (years) | 114 | 36.9 ± 16.1 | 86 | 36.1 ± 12.9 | 41 | 34.6 ± 13.6 | 0.85 |
| Duration of symptoms at enrollment(yrs) | 114 | 4.7 ± 6.7 | 86 | 5.1 ± 7.1 | 41 | 4.6 ± 4.5 | 0.70 |
| Initial infectious prodrome: (yes vs no) | 19 | 16.8% | 18 | 20.9% | 8 | 19.5% | 0.58 |
| Predominant symptom: | |||||||
| Nausea vs all others | 34 | 29.8% | 28 | 32.6% | 20 | 48.8% | 0.05 |
| Vomiting vs all others | 23 | 20.2% | 18 | 20.9% | 6 | 14.6% | 0.55 |
| Abdominal pain vs all others | 25 | 21.9% | 22 | 25.6% | 8 | 19.5% | 0.94 |
| Type of gastroparesis symptom onset: | 0.65 | ||||||
| Acute start | 57 | 50.0% | 41 | 47.7% | 23 | 56.1% | |
| Insidious start | 57 | 50.0% | 45 | 52.3% | 18 | 43.9% | |
| Nature of gastroparesis symptoms: | 0.005 | ||||||
| Chronic, but stable | 32 | 28.1% | 20 | 23.3% | 2 | 5.0% | |
| Chronic, but progressively worse | 26 | 22.8% | 33 | 38.4% | 22 | 55.0% | |
| Chronic with periodic exacerbations | 42 | 36.8% | 26 | 30.2% | 12 | 30.0% | |
| Cyclic pattern | 14 | 12.3% | 7 | 8.1% | 4 | 10.0% | |
| Gastroparesis severity: | 0.004 | ||||||
| Mild (grade 1) | 26 | 22.8% | 6 | 7.0% | 2 | 4.9% | |
| Compensated (grade 2) | 62 | 54.4% | 50 | 58.1% | 24 | 58.5% | |
| Gastric failure (grade 3) | 25 | 21.9% | 30 | 34.9% | 15 | 36.6% | |
| Gastric failure vs less severe | 25 | 21.9% | 30 | 34.9% | 15 | 36.6% | 0.03 |
| Irritable bowel syndrome or IBS§ | 0.34 | ||||||
| Yes, pending exam/test | 69 | 60.5% | 60 | 69.8% | 27 | 65.8% | |
| No | 45 | 39.5% | 26 | 30.2% | 14 | 34.2% | |
| Gastric emptying (scintigraphy): | |||||||
| Percent gastric retention at 2 hr. | 114 | 63.0 ± 16.8 | 86 | 62.0 ± 16.1 | 41 | 64.6 ± 16.1 | 0.80 |
| Percent gastric retention at 4 hr. | 113 | 26.3 ± 17.6 | 86 | 27.2 ± 17.9 | 41 | 35.7 ± 22.6 | 0.06 |
| Severity of delayed gastric emptying 4 hr: | 0.03 | ||||||
| Mild (0 – 20%) | 55 | 48.7% | 35 | 40.7% | 16 | 39.0% | |
| Moderate (21% – 35%) | 32 | 28.3% | 28 | 32.6% | 6 | 14.6% | |
| Severe (> 35%) | 26 | 23.0% | 23 | 26.7% | 19 | 46.3% | |
| Severity of symptoms:* | |||||||
| Nausea severity | 114 | 2.7 ± 1.4 | 86 | 3.9 ± 1.0 | 41 | 4.7 ± 0.6 | n/a |
| Retching severity | 114 | 1.1 ± 1.4 | 86 | 1.9 ± 1.6 | 41 | 3.8 ± 1.4 | n/a |
| Vomiting severity | 114 | 1.2 ± 1.7 | 86 | 1.9 ± 1.8 | 41 | 4.0 ± 1.0 | n/a |
| Stomach fullness severity | 114 | 3.0 ± 1.1 | 86 | 4.2 ± 0.8 | 41 | 4.7 ± 0.5 | n/a |
| Inability to finish meal severity | 114 | 3.0 ± 1.5 | 86 | 4.1 ± 1.0 | 41 | 4.4 ± 0.8 | n/a |
| Excessively full post meal severity | 114 | 3.0 ± 1.3 | 86 | 4.3 ± 0.9 | 41 | 4.6 ± 0.6 | n/a |
| Loss of appetite severity | 114 | 2.4 ± 1.4 | 86 | 3.6 ± 1.3 | 41 | 3.9 ± 1.2 | n/a |
| Bloating severity | 114 | 2.2 ± 1.4 | 86 | 4.0 ± 1.0 | 41 | 4.8 ± 0.4 | n/a |
| Visibly larger stomach severity | 114 | 1.6 ± 1.5 | 86 | 3.7 ± 1.3 | 41 | 4.5 ± 0.7 | n/a |
| Cardinal symptom index (GCSI)* | 114 | 2.1 ± 0.6 | 86 | 3.5 ± 0.3 | 41 | 4.4 ± 0.3 | n/a |
| Upper abdominal pain | 114 | 2.4 ± 1.7 | 86 | 3.8 ± 1.2 | 41 | 3.9 ± 1.4 | < 0.001 |
| Upper abdominal discomfort | 114 | 2.6 ± 1.6 | 86 | 3.9 ± 1.1 | 41 | 4.2 ± 1.0 | < 0.001 |
| Lower abdominal pain | 114 | 1.5 ± 1.5 | 86 | 2.6 ± 1.6 | 41 | 3.3 ± 1.5 | < 0.001 |
| Lower abdominal discomfort | 114 | 1.7 ± 1.5 | 86 | 2.7 ± 1.7 | 41 | 3.2 ± 1.5 | < 0.001 |
| GERD sub-scale | 114 | 1.5 ± 1.2 | 86 | 2.2 ± 1.4 | 41 | 3.1 ± 1.4 | < 0.001 |
| Constipation severity | 114 | 1.8 ± 1.6 | 86 | 2.8 ± 1.8 | 41 | 3.5 ± 1.7 | < 0.001 |
| Diarrhea severity | 114 | 1.6 ± 1.5 | 86 | 2.0 ± 1.8 | 41 | 2.4 ± 1.9 | 0.05 |
Severity of symptoms based on the Gastroparesis Cardinal Index Score from the PAGI-SYM (Patient Assessment of GI Symptoms) questionnaires, scores range from 0–5): Mild= 0–2.9, Moderate= 3.0–3.99, Severe= 4.0–5.0. Two subjects were excluded due to a missing score on the Stomach Fullness Severity score.
Gastroparesis cardinal symptom index (GCSI) = mean of sub-scores for nausea, postprandial fullness, and bloating
Means ± standard deviations or percents (%).
The significance of difference in categorical variables between groups was tested with either the Cochran-Armitage test for trend for ordered categories or Fisher’s exact test, or with the Wilcoxon rank sum test for continuous measures. All P values are two-sided.
Definitions:
Ever smoked regularly defined as smoking ≥ 20 packs of cigarettes in a lifetime or ≥ 1 cigarette per day for a year.
Overweight = BMI ≥ 25 kg/m2
ESR = Erythrocyte sedimentation rate
Irritable Bowel Syndrome or IBS diagnosis determined from the Rome III Diagnostic Questionnaire analyzed using an analysis program developed by the Rome Foundation (http://www.romecriteria.org/rome_iii_sas/).
Functional GI disorders
Patients with IG were also classified according to Rome III criteria for functional dyspepsia and irritable bowel syndrome (Supplemental Table 5). Overall, 86.0% of the IG patients fit criteria for functional dyspepsia with 91.0% meeting criteria for postprandial distress syndrome (PDS), 1.2% for epigastric pain syndrome, 34.2% for chronic idiopathic nausea, 38.7% for functional vomiting, and 64.6% for irritable bowel syndrome (IBS). There were no statistically significant differences in any of these classifications between females and males. PDS was significantly higher in patients with severely delayed GE (96%), compared to moderately (92%), or mild delay (87%), P=0.05. There was a slightly higher prevalence of IBS in patients with severe delay in gastric emptying (74% vs 68% vs 58%, P=0.04; Supplemental Table 6). With increasing severity of gastroparesis, there was a higher prevalence of functional vomiting (8.8% for grade 1, 38.0% for grade 2, and 53.5% for grade 3; p<0.001) and a trend for higher prevalence of postprandial distress syndrome (85.3% for grade 1, 90.5% for grade 2, and 95.8% for grade 3; p=0.06) (Supplemental Table 7).
DISCUSSION
This study highlights the clinical and physiologic features of patients with IG. The 243 patients comprising this multicenter report is the largest series of patients with IG. The study confirms that IG is a disease that particularly affects young women. Half of cases presented acutely, often in association with an initial infectious-like prodrome. The predominant symptom prompting evaluation was nausea in 34%, vomiting in 19%, and abdominal pain in 23%. Although the majority of patients were normal or even underweight, many patients were overweight or obese at time of enrollment despite having nausea and vomiting. Severe delay in gastric emptying was associated with more severe symptoms of vomiting, loss of appetite. Thus, IG has phenotypic variability with gender, body mass, type of symptom onset, degree of delay in gastric emptying, and gastroparesis severity.
Most patients with IG are women. Our finding that 88% of IG were female with a mean age of 41 years is similar to several other studies (2,3). Harrell et al (3) and Soykan et al (2) showed that approximately 80% of patients with gastroparesis were female. Females have been also reported to comprise the majority of patients with diabetic gastroparesis (76%) and postsurgical gastroparesis (89%) (2).
Why gastroparesis has a predilection for young female subjects is not known. In normal subjects, gastric emptying is affected by gender, menopausal status, and phase of the menstrual cycle (18,19). In this series of patients with IG, women tended to have a more severe delay in gastric emptying than males with IG. Postmenopausal status was more frequent with less severe gastroparesis severity. Stanghellini et al reported female sex was an independent factor associated with delayed gastric emptying in patients with functional dyspepsia (20). Females may have less of a reserve of ‘normal function’ than males and therefore be more likely to develop symptoms to a given insult. Women may have delayed gastric emptying compared to men due to differences in ovarian hormones, altered enteric transmission and decreased contractility of the antrum, altered gastric fundal accommodation and sensation (18,19,21,22). In our series of patients with IG, females had higher symptom scores than male patients for nausea and stomach fullness. In a survey of adults in the community, symptoms of early satiety and nausea were found to be more common in females than in males (23).
Half of the patients with IG in this series had an acute onset of symptoms, with 19% having an initial infectious prodrome. A viral infection has been suggested to precede the development of gastroparesis symptoms in some patients (24). In another series of patients with gastroparesis, 23% of the idiopathic patients presented after an acute viral gastroenteritis-like illness (2,25). In our series of IG, patients with acute onset had on average a shorter duration of symptoms and were more likely to have an initial infectious prodrome compared to those with insidious onset. These patients tended to have more gastric failure than those with insidious onset. This potential viral etiology for gastroparesis suggests viral-induced dysfunction of the components that affect gastric contractility: nerves, interstitial cells of Cajal, and/or smooth muscle. These patients with infectious-like gastroparesis have been reported to have slow resolution of their symptoms over several years, in contrast to individuals with IG without a viral trigger who tend to show less improvement over time (24).
The majority of IG patients were either normal body weight (47%) or underweight (8%). Interestingly, 46% of the IG patients were overweight or obese which was unexpected in these patients with chronic nausea and vomiting. Overweight and obese patients were also noted in the Harrell series (3). Of note, the prevalence of both overweight/obesity and obesity in this series of IG is lower than for adult white females in the general population (46% vs 58% for overweight/obese, 26% vs 31% for obese) (26). The reason for obesity in patients with delayed gastric emptying is unclear. Of the overweight patients, 30% were losing weight at the time of enrollment. The overweight patients had less severe loss of appetite and a lower score for inability to finish a meal compared to normal weight individuals. One explanation is that IG patients in the overweight or obese category are likely to have less severe anorexia and hence could ingest more calories. Greater body mass index and gastric volume have been associated with reduced satiation (32). On the other hand, obesity may be a cause rather than a consequence of the gastroparesis. Our study confirmed inflammatory markers are more common in obese/overweight patients and ongoing inflammation may be a contributory factor to the development of gastroparesis. Myenteric inflammation has been noted in the stomach of some patients with gastroparesis (28,29).
A common assumption is that symptoms of gastroparesis can be attributed to delay in gastric emptying. However, most investigations have observed only weak correlations between symptom severity and the degree of gastric stasis. In diabetics, the correlation between global gastric symptoms and gastric emptying is poor (30) with only postprandial fullness associating with delayed emptying (31). In functional dyspepsia, symptoms of early satiety, postprandial fullness, nausea, and vomiting are more prevalent in individuals with delayed gastric emptying (20,32). This study shows that patients with relatively severe delay in gastric emptying >35% retention at 4 hours had more severe nausea, vomiting, retching, and loss of appetite compared to patients with moderate or mild retention using univariable analysis, of which vomiting, loss of appetite, and higher GCSI scores persisted using multivariable logistic regression analysis.
There is overlap between gastroparesis and functional dyspepsia as both symptoms and gastric emptying results may meet definitions for both in some patients (4,41). Some patients with mild abdominal pain, nausea, vomiting, and evidence of delayed emptying are considered to have functional dyspepsia by some clinicians and gastroparesis by others. Functional dyspepsia is diagnosed by having symptoms of postprandial fullness, early satiation, epigastric pain/burning (33). Since these symptoms are non-specific and cover gastric symptomatology and since our patients had to have gastric symptoms to enter the study, it is not surprising that many IG patients met criteria for functional dyspepsia. Indeed, 86% of patients with IG met criteria for functional dyspepsia. Over 90% had PDS and the presence of PDS increased with the severity of the delay in gastric emptying. This relation of PDS with delayed gastric emptying has been reported previously (34).
Use of prokinetic agents, antiemetic agents, gastric acid suppressants, narcotic pain medications, and enteral/parenteral nutrition increased with increasing severity of delayed gastric emptying. This is not unexpected as these are the patients with more symptom burden. Use of narcotic analgesics which could potentially delay gastric emptying, however, was not associated with severely delayed gastric emptying in multivariable analysis.
The severity of gastroparesis was assessed by several methods including gastric retention on GES (13), a gastroparesis severity scale (4), and symptom severity using GCSI (7). Patients with severe gastric retention had more severe vomiting, loss of appetite, GCSI score, and more frequently used anti-emetics. Gastric failure was associated with nausea severity score, GCSI score, the use of antiemetic agents, and use of total/parenteral support, whereas being postmenopausal was associated with mild/compensated gastroparesis. Severe symptom severity was associated with increased gastric retention at 4 hours and depression. Thus, symptoms, gastric retention, current treatment, and psychosocial variables impact on the severity of the gastroparesis syndrome.
Patients in this multicenter study were recruited primarily from tertiary referral centers and may be more symptomatic and have higher number of co-morbid disorders than patients in the community. Interestingly, irritable bowel syndrome, fibromyalgia and major depression were greater in patients with severely delayed gastric emptying. Fibromyalgia by self report was also found to be present more often in patients with an insidious onset of gastroparesis, rather than an acute onset of symptoms. STAI and BDI scores tended to be higher in patients with severely delayed gastric emptying suggesting chronic gastroparetic symptoms in patients with IG can be associated with depression and anxiety. This is also seen in diabetic gastroparesis (35). Symptoms of functional dyspepsia, particularly PDS, have been associated with anxiety, depression, and somatization (36,37).
In conclusion, this study has shown that IG is a disorder that particularly affects young women. Half of cases presented acutely, often in association with an initial infectious prodrome. Patients with IG may be overweight or even obese. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a phenotypically diverse syndrome with substantial variations in symptom severity related to gender, body mass, type of symptom onset and degree of delayed gastric emptying and gastroparesis severity. The results provide the basis for studies to determine whether these variations of IG relate to differences in pathogenesis and whether they impact on clinical course and treatment outcome.
Supplementary Material
Footnotes
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The Gastroparesis Clinical Research Consortium (GpCRC) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974, U01DK074008).
Members of the Gastroparesis Clinical Research Consortium are listed in supplemental table 1.
No conflicts of interest exist.
Authors’ Contributions:
Henry P. Parkman: study conceptualization, patient recruitment, data interpretation, writing paper
William L. Hasler: study conceptualization, patient recruitment, writing paper
Linda Nguyen: study conceptualization, patient recruitment, writing paper
Pankaj J. Pasricha: study conceptualization, patient recruitment, writing paper
William J. Snape: study conceptualization, patient recruitment, writing paper
Gianrico Farrugia: study conceptualization, writing paper
Kenneth L. Koch: study conceptualization, patient recruitment, writing paper
Thomas L. Abell: study conceptualization, patient recruitment, writing paper
Richard W. McCallum: patient recruitment, writing paper
Katherine Yates: statistical analysis, writing paper
Linda Lee: study conceptualization, writing paper
Aynur Unalp-Arida: study conceptualization, writing paper
James Tonascia: study conceptualization, statistical analysis, writing paper
Frank Hamilton: study conceptualization, writing paper
REFERENCES
- 1.Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1592–1622. doi: 10.1053/j.gastro.2004.09.055. [DOI] [PubMed] [Google Scholar]
- 2.Soykan I, Sivri B, Sarosiek I, et al. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998;43:2398–2404. doi: 10.1023/a:1026665728213. [DOI] [PubMed] [Google Scholar]
- 3.Harrell SP, Studts JL, Dryden GW, et al. A novel classification scheme for gastroparesis based on predominant-symptoms presentation. J Clin Gastroenterol. 2008;42:455–459. doi: 10.1097/MCG.0b013e31815ed084. [DOI] [PubMed] [Google Scholar]
- 4.Abell TL, Bernstein VK, Cutts T, et al. Treatment of gastroparesis: a multidisciplinary clinical review. Neurogastroenterol Motil. 2006;18:263–283. doi: 10.1111/j.1365-2982.2006.00760.x. [DOI] [PubMed] [Google Scholar]
- 5.Rentz AM, Kahrilas P, Stanghellini V, et al. Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders. Qual Life Res. 2004;13:1737–1749. doi: 10.1007/s11136-004-9567-x. [DOI] [PubMed] [Google Scholar]
- 6.Revicki DA, Rentz AM, Dubois D, et al. Gastroparesis Cardinal Symptom Index (GCSI): development and validation of a patient reported assessment of severity of gastroparesis symptoms. Qual Life Res. 2004;13:833–844. doi: 10.1023/B:QURE.0000021689.86296.e4. [DOI] [PubMed] [Google Scholar]
- 7.Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther. 2003;18:141–150. doi: 10.1046/j.1365-2036.2003.01612.x. [DOI] [PubMed] [Google Scholar]
- 8.Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996;67:588–597. doi: 10.1207/s15327752jpa6703_13. [DOI] [PubMed] [Google Scholar]
- 9.Richter P, Werner J, Heerlein A, et al. On the validity of the Beck Depression Inventory. A review. Psychopathology. 1998;31:160–168. doi: 10.1159/000066239. [DOI] [PubMed] [Google Scholar]
- 10.Spielberger C, Gorsuch R, Lushene R. Manual for the state-trait anxiety inventory. Palo Alto, CA: Consulting Psychologists Press; 1970. [Google Scholar]
- 11.Drossman DA, Corazziari E, Delvaux M, et al. Rome III and the Functional Gastrointestinal Disorders. (3rd edition) 2006 [Google Scholar]
- 12.Tougas G, Eaker EY, Abell TL, et al. Assessment of gastric emptying using a low fat meal: establishment of international control values. Am J Gastroenterol. 2000;95:1456–1462. doi: 10.1111/j.1572-0241.2000.02076.x. [DOI] [PubMed] [Google Scholar]
- 13.Abell TL, Camilleri M, Donohoe K, et al. Consensus Recommendations for Gastric Emptying Scintigraphy. A Joint Report of the Society of Nuclear Medicine and The American Neurogastroenterology and Motility Society. Am J Gastroenterology. 2008;103:753–763. doi: 10.1111/j.1572-0241.2007.01636.x. [DOI] [PubMed] [Google Scholar]
- 14.Camilleri M. Diabetic Gastroparesis. N Engl J Med. 2007;356:820–829. doi: 10.1056/NEJMcp062614. [DOI] [PubMed] [Google Scholar]
- 15.Agresti A. Categorical Data Analysis. New York: John Wiley & Sons, Inc.; 1990. [Google Scholar]
- 16.Hosmer D, Lemeshow S. Applied Logistic Regression. Second ed. New York: John Wiley & Sons, Inc.; 2000. [Google Scholar]
- 17.SAS Institute, Inc. SAS software, version 9.1 of the SAS system for Windows. Cary, NC: 2002. [Google Scholar]; StataCorp. Stata statistical software: release 11. College Station, TX: 2009. [Google Scholar]
- 18.Hutson WR, Roehrkasse RL, Wald A. Influence of gender and menopause on gastric emptying and motility. Gastroenterology. 1989;93:934–940. doi: 10.1016/0016-5085(89)90758-0. [DOI] [PubMed] [Google Scholar]
- 19.Mones J, Carrio I, Calabuig R, et al. Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers. Eur J Nucl Med. 1993;20:600–602. doi: 10.1007/BF00176554. [DOI] [PubMed] [Google Scholar]
- 20.Stanghellini V, Tosetti C, Paternic A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996;110:1036–1042. doi: 10.1053/gast.1996.v110.pm8612991. [DOI] [PubMed] [Google Scholar]
- 21.Mearadji B, Penning C, Vu MK, et al. Influence of gender on proximal gastric motor and sensory function. Am J Gastroenterol. 2001;96:2066–2073. doi: 10.1111/j.1572-0241.2001.03940.x. [DOI] [PubMed] [Google Scholar]
- 22.Gangula PRR, Maner WL, Micci M-A, et al. Diabetes induced sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol GI. 2007;292:G725–G733. doi: 10.1152/ajpgi.00406.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol. 2005;3:543–552. doi: 10.1016/s1542-3565(05)00153-9. [DOI] [PubMed] [Google Scholar]
- 24.Oh JJ, Kim CH. Gastroparesis after a presumed viral illness: clinical and laboratory features and natural history. Mayo Clin Proc. 1990;65:636–642. doi: 10.1016/s0025-6196(12)65125-8. [DOI] [PubMed] [Google Scholar]
- 25.Bityutskiy LP, Soykan I, McCallum RW. Viral gastroparesis: a subgroup of idiopathic gastroparesis- clinical characteristics and long-term outcomes. Am J Gastroenterol. 1997;92:1501–1504. [PubMed] [Google Scholar]
- 26.NHANES 2001–2004. US: NCHS Health; 2006. [Google Scholar]
- 27.Delgado-Aros S, Cremonini F, Castillo JE, et al. Independent influences of body mass and gastric volumes on satiation in humans. Gastroenterology. 2004;126:432–440. doi: 10.1053/j.gastro.2003.11.007. [DOI] [PubMed] [Google Scholar]
- 28.Harberson J, Thomas R, Harbison S, Parkman HP. Gastric neuromuscluar pathology of gastroparesis: analysis of full-thickness antral biopsies. Dig Dis Sci. 2010;55:359–370. doi: 10.1007/s10620-009-1071-2. [DOI] [PubMed] [Google Scholar]
- 29.Lurken MS, Kashyap P, Parkman HP, et al. The pathological basis of gastroparesis. Gastroenterology. 2008;134(4) Suppl 1:A-536. [Google Scholar]
- 30.Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in insulindependent diabetes mellitus. J Gastroenterol Hepatol. 1986;1:97–113. [Google Scholar]
- 31.Jones KL, Russo A, Stevens JE, et al. Predictors of delayed gastric emptying in diabetes. Diabetes Care. 2001;24:1264–1269. doi: 10.2337/diacare.24.7.1264. [DOI] [PubMed] [Google Scholar]
- 32.Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783–788. doi: 10.1111/j.1572-0241.2003.07389.x. [DOI] [PubMed] [Google Scholar]
- 33.Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466–1479. doi: 10.1053/j.gastro.2005.11.059. [DOI] [PubMed] [Google Scholar]
- 34.Kindt S, Dubois D, Van Oudenhove L, et al. Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia. Neurogastroenterol Motil. 2009;21 doi: 10.1111/j.1365-2982.2009.01374.x. 1183-e105. [DOI] [PubMed] [Google Scholar]
- 35.Hasler WL, Parkman HP, Wilson LA, et al. Psychological dysfunction is associated with symptom severity but not disease etiology or degree of gastric retention in patients with gastroparesis. Am J Gastroenterol. 2010 Jun 29; doi: 10.1038/ajg.2010.253. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatization? Gut. 2008;57:1666–1673. doi: 10.1136/gut.2008.158162. [DOI] [PubMed] [Google Scholar]
- 37.Aro P, Talley NJ, Storskrubb T, et al. Association with uninvestigated and functional dyspepsia (Rome III) in a random adult population: the Kalixanda study. Gastroenterology. 2009;137:94–100. doi: 10.1053/j.gastro.2009.03.039. [DOI] [PubMed] [Google Scholar]
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