Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial

Abstract

Abnormal gastric accommodation (GA) and gastric emptying contribute to pathophysiology in functional dyspepsia (FD). Secretin is a key regulator of GA in animal studies. Our aim was to study the effects of secretin on gastric motility, satiation, postprandial symptoms, and key hormones. We performed two double-blind, randomized, saline-controlled crossover trials in 10 healthy volunteers and 10 patients with FD by Rome IV criteria. We used measured GA (by validated SPECT method) after a 111In radiolabeled Ensure 300-mL meal and quantified gastric emptying for 30 min by scintigraphy. Satiation was measured by volume to fullness (VTF) and maximum tolerated volume (MTV) on an Ensure nutrient drink test and postprandial symptoms 30 min post-MTV. Fasting and postprandial GLP-1, GIP, and HPP were measured. The ages and sex distribution of healthy controls and patients with FD were similar. Compared with placebo, secretin delayed gastric emptying at 30 min in both health [−11% (−16, −4), P = 0.004]; and FD [−8% (−9, 0), P = 0.03]. Satiation (VTF and MTV), GA, and plasma levels of GLP-1, GIP, and HPP did not differ between treatment arms in health or FD. On ANCOVA analysis (adjusting for age and sex), secretin did not consistently increase postprandial symptoms in health or FD. Secretin delayed gastric emptying in both health and FD without significantly altering GA, VTF, or MTV or selected hormones. Thus, secretin receptor activation may provide a novel therapeutic mechanism for patients with FD and rapid gastric emptying. NEW & NOTEWORTHY The naturally occurring hormone secretin retards gastric emptying of solids without deleteriously affecting gastric accommodation, satiation, other upper gastrointestinal hormones, or postprandial symptoms. Given these findings, a subset of patients with rapid gastric emptying (e.g., the estimated 20% of patients with functional dyspepsia) could be candidates for treatments that stimulate a secretin receptor such as sacubitril, which inhibits neprilysin, an enzyme that degrades secretin.

Association Between Food Intake and Gastrointestinal Symptoms in Patients With Obesity

“…Participants completed the abridged Bowel Disease Questionnaire, a 16-item form that has been used to evaluate various functional GI symptoms ( Supplementary Material ). 32 …”

Nocebo response intensity and influencing factors in the randomized clinical trials of functional dyspepsia: A systematic review and meta‐analysis

“…The average rate of nasopharyngitis among the studies was 9.3% (41/442), as reported by Matsueda et al 26 The average rate of constipation was 6% (95% CI 1%-10%; P < 0.01), including 31 patients in eight studies 15,16,18,19,22,24,28,32 (Figure 4A). The average rate of headache was 5% (95% CI 3%-8%; P = 0.02), with 11 studies 12,14,18,[20][21][22][23]25,34,35,37 including 36 patients (Figure 4B). While the average rate of diarrhea was 3% (95% CI 1%-4%; P < 0.01), with 10 studies 12,14,18,19,21,22,25,26,29,37 including 48 patients (Figure 4C).…”

Gastrointestinal hormones and regulation of gastric emptying

“…It is involved in the small bowel pH regulation through inducing bicarbonate secretion and suppression of gastric acid secretion. In addition, secretin induces gastric relaxation, delays gastric emptying and induces secretion of pancreatic enzymes [93 ▪ ,94] (Fig. 2).…”