Studies were performed in fifteen healthy volunteers [male:female, 12:4; age: 40 ± 5 years; body mass index (BMI): 26.5 ± 1.6 kg/m²]. Subjects were screened and excluded if they were diabetic, pregnant or breast feeding, had previous gastrointestinal surgery, a history of gastrointestinal disease or taking medications known to alter gastrointestinal motility. None of the subjects regularly smoked tobacco or drank more than 20 g of alcohol per day.

The protocol was approved by the research ethics committee of the Royal Adelaide Hospital, and each subject gave written informed consent prior to the commencement of the study.

Multi-lumen perfusion manometry: APD motility was assessed by a 100-cm multi-lumen perfusion manometric assembly (outer diameter 3.5 mm; Mui Scientific, Ontario, Canada). The assembly incorporated 15 pressure recording channels (side-holes spaced 1.5 cm apart), with a 4.5 cm sleeve-sensor, and an infusion port. Correct placement of the sleeve across the pylorus was determined using continuous measurement of the antro-duodenal transmucosal potential difference (TMPD) gradient[8]. The assembly was positioned so that five side holes (A1-A5) were located in the gastric antrum and seven in the proximal duodenum (Figure 1). The infusion port was located at the catheter tip to enable the delivery of enteral feed directly into the duodenum 9 cm distal to the pylorus. Thirteen manometric lumina were perfused with degassed water at a rate of 0.04 mL/min except for the sleeve perfused at a rate of 0.15 mL/min. To monitor TMPD two channels on either end of the sleeve were perfused with degassed 0.9% saline. Pressure and TMPD data were recorded on a computer using purpose written software program (Medical Measurement Systems, Enschede, The Netherlands)[8].

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Figure 1 Representative trace of intraluminal motility at (A) 0 kcal/min and at (B) 1. 5 kcal/min. Occlusive contraction waves commence in the antrum and propagate through the duodenum. At 1.5 kcal/min isolated pyloric pressure waves occurred more frequently and a reduction in propagated antral contractility was observed.

Blood glucose concentration: As hyperglycaemia has a major impact on gastric motility[9], blood glucose concentrations were measured using a portable glucometer (Precision Plus, Abbott Laboratories, Bedford, United States) every 20 min throughout the study.

Subjects were studied in the gastrointestinal motility laboratory of the Royal Adelaide Hospital after an overnight fast. The manometric catheter was inserted into an anaesthetised nostril and passed into the stomach. The catheter passed into the duodenum assisted by spontaneous peristalsis. A cannula was inserted into an antecubital vein for blood sampling.

Each subject received intraduodenal infusions of 50% glucose solution (Pharmalab NSW Australia) diluted in water at: (1) 0.5 kcal/min; (2) 1 kcal/min; (3) 1.5 kcal; and (4) 0 kcal/min (0.9% saline only). Each solution was prepared in separate 20 mL syringes by a study investigator who was not involved in the data analysis and infused at a rate of 1 mL/min. Randomisation of glucose load was computer generated. Each syringe was then covered by the investigator preparing the syringes and labelled according to the randomisation schedule. The syringe was connected to the manometric catheter using opaque minimal volume extension tubing to ensure blinding of the research staff.

Following correct positioning of the catheter sleeve across the pylorus, a 20 min fasting period commenced. At the end of the fasting period the scheduled load was infused directly into the duodenum, via a volumetric syringe driver [Terumo Syringe Pump (STC-523), Medtel Australia], followed by a 40 min “washout” period of 0.9% saline (1 mL/min). A similar schedule was followed for all glucose loads. Blood samples were taken every 20 min throughout the study period to measure blood glucose concentrations.

Manometric data were imported into Acqknowledge 3.2.7 and were analysed manually. The frequencies of APD pressure waves were determined as previously described[8]. In brief, pressure waves were included in the analysis when a rise in intraluminal pressure was greater than the minimum amplitude over the appropriate time-period and when the assembly was positioned correctly according to established TMPD criteria. Migrating motor complex (MMC) phase III activity associated pressure waves were considered to be representative of fasting motor patterns and were counted as zero for the period of phase III activity. Antral phase III MMC activity was defined as rhythmic pressure wave activity occurring at a maximum frequency (three pressure waves per minute) for at least one minute with a temporal relationship with duodenal activity. Duodenal phase III MMC was defined as a maximum frequency of 10-12 pressure waves/min for at least 2 min[8].

A pressure wave in the antrum and pylorus was defined as a pressure rise of 10 mmHg or more from baseline and lasting between 6.1 and 20 s[10]. Isolated pyloric pressure waves (IPPWs) were defined as pressure waves at least 10 mmHg amplitude recorded only in the sleeve channel[5]. A duodenal PW was defined as a pressure rise of 6 mmHg or more from baseline and lasting between 0.8 and 7 s[10]. Change in pyloric tone (basal pyloric pressure) was calculated as the difference in baseline pressure in the sleeve sensor from the duodenum[11] at 4-min intervals and presented as mean over 20 min.

Data are presented as mean ± SE. Repeated-measures analysis of variance (RM-ANOVA) were used to test for effects on pressure wave activity and pyloric tone of different caloric loads. Residuals were normally distributed and, furthermore, analyses using the equivalent non-parametric test (Friedman) remained significant. On testing there was no order effect apparent. Differences at the level of P < 0.05 were considered significant and allowed post-hoc comparison between loads which were corrected according to Bonferroni adjustment.

An example of a manometric trace at two different loads is shown in Figure 1.

Antral pressure waves: The effect of glucose loads on antral pressure wave activity is shown in Figure 2A. Increasing the caloric load had an effect on antral wave frequency (P = 0.007) with marked attenuation of antral pressure wave activity at 1.5 kcal/min, when compared to 0 kcal/min (0 kcal/min: 7.5 ± 1.8 waves/20 min vs 1.5 kcal: 2.8 ± 1.3 waves/20 min; P = 0.007).

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Figure 2 Antral, isolated pyloric, duodenal pressure waves and pyloric tone at differing caloric loads. A: Reduction in antral motility occurred with increasing glucose load with marked attenuation of antral pressure wave activity at 1.5 kcal/min, when compared to 0 kcal/min (0 kcal/min: 7.5 ± 1.8 waves/20 min vs 1.5 kcal: 2.8 ± 1.3 waves/20 min; P = 0.007); B: The frequency of isolated pyloric pressure waves increased with increasing caloric load. The number of waves/20 min were statistically different between 0 and 1.0 kcal/min (0 kcal/min: 8.0 ± 2.3 waves/20 min vs 1.0 kcal/min: 25.9 ± 3.7 waves/20 min; P = 0.002); C: The nutrient load did not effect duodenal wave frequency when comparing 0 kcal/min to 1.5 kcal/min (0 kcal/min: 24.4 ± 4.7 waves/20 min vs 1.5 kcal/min: 34.7 ± 4.9 waves/20 min; P = 0.22); D: Pyloric tone increased in response to increasing caloric loads (P = 0.015). Between 0.5 and 1.5 kcal/min the difference was significant (0.5 kcal/min: -0.4 ± 1.1 mmHg vs 1.5 kcal/min: 3.1 ± 1.3 mmHg; P = 0.008).

IPPWs: The effects of glucose loads on IPPW activity are shown in Figure 2B. The frequency of IPPWs were affected by caloric load (P < 0.001) with a substantial increase in pressure waves occurring with increasing nutrient (0 kcal/min: 8.0 ± 2.3 waves/20 min vs 1.0 kcal: 25.9 ± 3.7 waves/20 min; P = 0.002). The increasing frequency of IPPW during glucose infusion occurred in a dose dependent fashion with 1.0 kcal/min the observed threshold to stimulate the pylorus (0 kcal/min: 8.0 ± 2.3 waves/20 min vs 0.5 kcal/min: 14.2 ± 2.7 waves/20 min; P = 0.294; but 0.5 kcal/min 14.2 ± 2.7 waves/20 min vs 1.0 kcal: 25.9 ± 3.7 waves/20 min; P = 0.037).

Duodenal pressure waves: The effects of glucose loads on duodenal wave activity are shown in Figure 2C. There was a difference between treatments over time in duodenal motor wave activity with different caloric loads (P = 0.012). However, post-hoc testing did not reveal a difference between the individual loads (0 kcal/min: 24.4 ± 4.7 waves/20 min vs 34.7 ± 4.9 waves/20 min, P = 0.22; and 0.5 kcal/min 21.7 ± 3.3 waves/20 min vs 34.7 ± 4.9 waves/20 min, P = 0.058).

Pyloric tone: The effects of glucose loads on pyloric tone are shown in Figure 2D. There was an observed difference between treatments in pyloric tone (P = 0.015). The difference between 0 and 1.5 kcal/min was significant prior (P = 0.035), but not following Bonferroni adjustment (0.0 ± 0.9 vs 3.12 ± 1.3; P = 0.207). However, the difference remained significant between 0.5 and 1.5 kcal/min (-0.4 ± 1.1 vs 3.1 ± 1.3; P = 0.008).

Blood glucose concentrations were similar prior to commencing each infusion (0, 0.5, 1.0 and 1.5 kcal/min: 6.5 ± 0.3 mmol/L, 5.9 ± 0.2 mmol/L, 5.8 ± 0.3 mmol/L vs 5.7 ± 0.2 mmol/L; P = 0.625) and at the completion of the infusion (5.9 ± 0.2, 5.9 ± 0.2, 6.4 ± 0.3 vs 6.2 ± 0.2; P = 0.079).

Emptying of liquid nutrient from the stomach is regulated by antro-pyloro-duodenal (APD) motor activity. Nutrient within the small intestine initiates a feedback loop that affects motility of the APD area. Recent data suggest that the “doses” of lipid nutrient initiating these motor changes in health are much less than previously recognised. Likewise small intestinal carbohydrate infusions at rates that are within normal gastric emptying rates have marked effects on the APD unit. However, the specific threshold and/or hierarchy of the APD response to nutrient stimulation are unknown. The aim of this study was to assess the responses of the distal stomach to graded small intestinal nutrient stimulation in health.

The specific threshold and/or hierarchy of the APD response to nutrient stimulation are unknown.

This study shows that modulation of each component of the APD unit is hierarchical and dependent on caloric load; initially resistance to trans-pyloric flow occurs with isolated pyloric pressure waves and, subsequently, antral propulsive force decreases.

The implication of this finding is that small intestinal delivery of nutrient, even within so-called “normal” gastric emptying rates has a substantial effect on APD motor patterns.

APD manometry is a technique used to measure luminal occlusive contractions, which result in peristaltic flow.

This is a continuum of authors’ previous works and tested a role of diet in the duodenum in the stimulation of the APD motor response. It’s worth to publish on this journal as a brief report or communication.