Interdigestive antroduodenal motility and gastric acid secretion

Background:

In humans, interdigestive acid secretion and antroduodenal motility are closely related with cyclic variations in acid secretion, synchronous with the various phases of the migrating motor complex (MMC). Duodenal acidification inhibits antral motility, but little is known about the effect of acute acid inhibition on antroduodenal motility.

Aim:

To study the effect of acute acid inhibition on antroduodenal motility.

Subjects:

Ten healthy volunteers (four men and six women; age range 20–31 years).

Methods:

Antroduodenal motility (perfusion manometry) and gastric acid secretion (continuous aspiration with recovery marker) were measured simultaneously. Each subject was studied twice in random order during (1) intravenous infusion of saline for one–two complete MMC cycles and (2) during acute acid inhibition with intravenous famotidine (bolus 20 mg, continuous infusion 4 mg/h) for one–two complete MMC cycles or at least 240 min.

Results:

In the saline study, acid output in phase III (2.1 ± 0.3 mmol/10 min) and late phase II (1.7 ± 0.2 mmol/10 min) was significantly (P < 0.05) increased over early phase II and phase I (1.2 ± 0.2 and 1.2 ± 0.2 mmol/10 min, respectively). Famotidine increased gastric pH to above pH 6 within 30 min. After acid inhibition, duration of MMC cycle during famotidine (106 ± 8 min) was not significantly different from the saline experiment (133 ± 14 min). Phase distribution of the MMC cycle was not significantly different between famotidine (I, II and III: 12 ± 3, 82 ± 3 and 5 ± 1%) and saline (I, II and III: 13 ± 3, 83 ± 3 and 4 ± 1%).

Conclusions:

Gastric acid secretion varies cyclically with interdigestive antroduodenal motility. Acute acid inhibition with intravenous famotidine does not significantly affect interdigestive antroduodenal motility.

     

Diabetes mellitus,genetic variants in the insulin-like growth factor pathway and colorectal cancer risk

Genetic variation in the insulin-like growth factor (IGF) pathway may further increase the risk of colorectal cancer (CRC) associated with type 2 diabetes mellitus (T2DM). Joint effects of T2DM and genetic variation in the IGF pathway on CRC risk can increase mechanistic insights. Participants from the Netherlands Cohort Study (n = 120, 852) completed a baseline questionnaire in 1986 when 55–69 years old (case–cohort, n_subcohort = 5,000, n_cases = 3,441 after 16.3 years follow-up). Self-reported DM at baseline with onset at ≥30 years was classified as T2DM. Eighteen single nucleotide polymorphisms (SNPs) from the IGF pathway were aggregated in a genetic risk score (GRS). Cox proportional hazard ratios (HRs) for CRC were estimated according to combinations of T2DM status with GRS tertiles and categories of an IGF1 19-CA repeat polymorphism. Baseline T2DM prevalence was 3.1% in subcohort members and 3.8% in CRC cases. Comparison of combined categories with non-T2DM individuals in the lowest GRS tertile as reference showed that those in the highest GRS tertiles with and without T2DM had significantly increased CRC risks, particularly those with T2DM (HR = 2.28, 95% CI: 1.11, 4.66). As compared to IGF1 19-CA wild-type carriers without T2DM, carrying two IGF1 19-CA variant repeat alleles were associated with a significantly decreased CRC risk in those without T2DM (HR = 0.76, 95% CI: 0.63–0.91). This association was absent when T2DM was present. Our study of joint effects indicated that the presence of unfavorable alleles in the IGF pathway may further increase the risk of CRC associated with T2DM.