A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia.

BACKGROUND & AIMS: Dyspepsia is common in clinical practice and in the community. The relationship of the symptoms to meals and the pathophysiology in community dyspeptic patients is unclear. The purpose of this study was to measure symptoms, demographic features, and gastric motor and sensory functions associated with dyspepsia in the community. METHODS: A Modified Bowel Disease Questionnaire was mailed to a random sample of Olmsted County, MN, residents. Dyspeptic patients and healthy controls identified among community respondents completed further questionnaires, Helicobacter pylori serology, gastric emptying by scintigraphy, gastric accommodation by 99mTc-single-photon emission computed tomography imaging, and postprandial symptoms and satiation by a nutrient drink test. RESULTS: A total of 34.1% of community respondents reported dyspepsia within the past year, frequent (at least 25% of the time in the past year) in 17.5%, and 18.4% reported meal-related dyspepsia. Dyspepsia was frequent and related to meals in 10.8% of respondents. Compared with nondyspeptic controls, community dyspepsia was associated with higher aggregate symptom scores and bloating after a fully satiating meal. Community dyspepsia also was associated with higher somatization scores (P = .001), reporting of other somatic symptoms (P = .07), and general severity score on the symptom checklist 90 (P = .01), but not with disordered motor or sensory function. Gastric volumes, gastric emptying, and maximum tolerated volumes were not significantly different between community controls and dyspeptic patients. CONCLUSIONS: Meal-related dyspepsia is an important component of dyspepsia in the community. Community dyspeptic patients have higher symptom scores after a fully satiating meal, consistent with gastric hypersensitivity. This is associated with higher somatization scores rather than disorders of gastric emptying or volumes.

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers.

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.