The authors have declared that no competing interests exist.
Conceived and designed the experiments: HY AF SU. Performed the experiments: HY TY SM AF MY YM SS HO SU KM HM TT. Analyzed the data: VNT HY AF MY YM SS HO SU KM. Contributed reagents/materials/analysis tools: VNT HY AF MY YM SS HO SU HM TT. Wrote the paper: VNT HY AF SU HM TT.
Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been suggested as a possible mechanism underlying the improvement in type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG). However, the reason for enhanced GLP-1 secretion during glucose challenge after LSG remains unclear because LSG does not include intestinal bypass. In this study, we focused on the effects of LSG on GLP-1 secretion and intestinal motility during the oral glucose tolerance test (OGTT) using cine magnetic resonance imaging (MRI) before and 3 months after LSG.
LSG was performed in 12 obese patients with a body mass index >35 kg/m2. Six patients had T2DM. OGTT was performed before and 3 months after the surgery. Body weight, hemoglobin A1c (HbA1c), and GLP-1 levels during OGTT were examined, and intestinal motility during OGTT was assessed using cine MRI.
Body weight was significantly decreased after surgery in all the cases. HbA1c was markedly decreased in all the diabetic subjects. In all cases, GLP-1 secretion during OGTT was enhanced and cine MRI showed markedly increased intestinal motility at 15 and 30 min during OGTT after LSG.
LSG leads to accelerated intestinal motility and reduced intestinal transit time, which may be involved in the mechanism underlying enhanced GLP-1 secretion during OGTT after LSG.
Morbid obesity is currently a worldwide health problem because it promotes the development of various diseases, including cardiovascular disease and type 2 diabetes mellitus (T2DM), which considerably increase mortality. However, current therapies, such as diet, exercise, lifestyle modification, and medication, seem to be insufficient for treating morbid obesity.
There is strong evidence that bariatric surgery can cure not only obesity but also its comorbidities. Laparoscopic sleeve gastrectomy (LSG) is typically performed before biliopancreatic diversion in the treatment of morbid obesity for high-risk patients, but LSG has recently been applied as a single-stage procedure because of its technical simplicity, remarkable postoperative weight loss, and T2DM remission
However, the mechanism underlying the improvement in T2DM after LSG has not been elucidated until now. Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be a mechanism underlying the improvement in T2DM after LSG
A previous study with scintigraphy
Twelve obese patients with a body mass index (BMI) >35 kg/m2 were recruited into the study. Among these, 6 patients had T2DM and 2 diabetic patients had hemoglobin A1c (HbA1c) levels >7.8%. Patients were eligible to participate in the study if they were between 20 and 65 years of age, and had a BMI between 30 and 35 kg/m2 with T2DM. Candidates were excluded if they had type 1 diabetes, severe diabetic complications, or a contradiction for either surgery. We also excluded subjects with a history of gastrointestinal motility disorders or inflammatory bowel disease. In addition to any assessments required for inclusion, each participant was assessed by a multidisciplinary team. The Ethics Review Committee of Shiga University of Medical Science (Shiga, Japan) approved all protocols described in this study, and all participants provided written informed consent.
LSG was performed with the patient in a supine position using a standard 5-port laparoscopic technique with a 45-Fr gastric tube to calibrate the sleeve, and dissection of the greater curvature began approximately 5–6 cm from the pylorus, as described previously
On the first day after surgery, the patient was administered a clear liquid diet, which progressed to a complete liquid diet for 2 weeks, followed by a soft diet for 1 week, eventually advancing to a regular diet.
OGTT was performed 1 week before and 3 months after the surgery. GLP-17–36 levels during OGTT were measured using commercially available enzyme-linked immunosorbent assay kits (Linco Research Inc., St. Charles, MO, USA).
MRI examinations were performed for each patient 1 week before and 3 months after the surgery. After 8 h of fasting, MRI was performed before as well as 15 and 30 min after oral intake of 225 mL of fluid containing 75 g of glucose. Imaging was performed as reported previously
Based on the cine MRI, 2 bowel segments, one located in the left upper quadrant as representative of the jejunal loops and the other located in the right lower quadrant as representative of the ileal loops, were chosen for assessment of contraction. In this process, bowel loops with a degree of distension similar to the rest of the loops in the same quadrant as well as remaining in the image plane during the sequential imaging without displacement out of the image plane were chosen for assessment. Frequencies of bowel contractions were counted visually on a monitor using cine MRI. Arrival of the orally administered fluid to the jejunum, ileum, and terminal ileum was assessed within each sequence (15 and 30 min after glucose intake) by the presence or absence of bowel distension and high signal fluid. The presence or absence of distension of the jejunal and ileal loops was also judged, and contraction frequencies were compared between distended and collapsed bowel loops after surgery.
We analyzed the data using SPSS version 17.0 software (SPSS Inc., Chicago, IL, USA) and the paired sample
The percentage of excess weight loss (%EWL) at 3 months after the surgery was 48% ±22% (
In both the nondiabetic and diabetic patients, GLP-17–36 secretion during OGTT was significantly enhanced. AUC of GLP-17–36 was significantly higher after LSG than before LSG (
Cine MRI scans before and 3 months after LSG were obtained in 9 of the 12 patients because of 3 patients refused examination, including 2 diabetic patients and 1 nondiabetic patient. Cine MRI was tolerated well in all 9 patients and provided sufficient quality of cine images to analyze bowel contractions and the state of small bowel transit. There was no significant difference in mean frequencies of contractions of the jejunum and ileum prior to glucose intake between before and after LSG. However, their contractions significantly increased at 15 and 30 min after glucose intake after LSG compared with those before LSG (
The percentage of patients whose glucose fluid reached the jejunum, ileum, and ileum terminal at 15 and 30 min after fluid intake was markedly increased after LSG (
In addition, the mean frequency of contractions of fluid-distended jejunum and ileum loops (6.1/min and 7.4/min, respectively) was significantly higher than that of contractions of collapsed jejunum and ileum loops (0.5/min and 1.4/min, respectively) (
We included video clips of 4 representative patients as a demonstration of changes in cine MRI after LSG (
Our study offers novel insights into the effects of LSG on intestinal motility using the novel cine MRI method. In summary, we demonstrated that LSG enhances GLP-17–36 secretion and accelerates intestinal motility and propagation of the test fluid during OGTT.
Previous studies have shown that LSG leads to improvement in glucose tolerance, which may be explained by the decrease in insulin resistance due to weight loss
To date, the reason for enhanced GLP-1 secretion after LSG still remains unclear because LSG does not include intestinal bypass. Patel RT et al. have recently depicted the role of the duodenum in promoting high levels of GLP-1 following sleeve gastrectomy
Our main scope was to evaluate postoperative alterations in small intestinal motility, an area much more obscure than the stomach. There are several ways to monitor and assess small bowel motility function, such as transit time analysis
Thus, cine MRI can enable visualization of movement of the entire intestine in real time before and after glucose intake. Using this novel method, we showed that intestinal motility was markedly accelerated and small bowel transit time was reduced after glucose intake in all patients following LSG. This acceleration of contraction was concurrently observed with faster arrival of the intake fluid and intestinal distension. The arrival of the glucose fluid might have changed the patterns of bowel contraction from a fasting pattern to a postprandial pattern. As demonstrated by Wakamiya et al.
Gastrointestinal motility is an integrated process that includes myoelectrical and contractile activities, tone, compliance, and transit
In agreement with previous studies
We acknowledged several limitations in the present study. As a first pilot study, we only enrolled 12 patients, and of these, only 9 underwent cine MRI. In addition, our reliance on liquid test meals appears to be the most serious limitation; thus, evaluation of gastrointestinal motility after ingestion of a solid test meal is required before our results can be generalized.
Nevertheless, for the first time, we clearly demonstrated that intestinal motility was markedly accelerated and bowel transit time reduced after LSG using a novel method.
In conclusion, LSG leads to accelerated intestinal motility and reduced intestinal transit time, which may be involved in the mechanism underlying enhanced GLP-1 secretion during OGTT after LSG. However, the exact mechanisms by which LSG affects intestinal motility remain unknown; therefore, further studies are needed to clarify this issue.
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A part of this work was presented by Hiroshi Yamamoto in International Federation for the Surgery of Obesity and metabolic disorders-Asian Pacific Chapter (IFSO-APC) in Rusutsu, Japan, 2011.