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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 5  |  Page : 5-10

Laparoscopic jejunoileal side-to-side anastomosis for the treatment of type 2 diabetes mellitus in Chinese patients with a body mass index of 24–32 kg/m2


Department of Oncology Surgery, Xuzhou Central Hospital, Affiliated Hospital of Medical College of Southeast University, Xuzhou 221009, People's Republic of China

Date of Web Publication7-Oct-2016

Correspondence Address:
Minkang Zhang
Department of Oncology Surgery, Xuzhou Central Hospital, Affiliated Hospital of Medical College of Southeast University, Xuzhou 221009
People's Republic of China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.191618

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 > Abstract 


Objective: Laparoscopic jejunoileal side-to-side anastomosis (LJISSA) is an upcoming procedure that offers good metabolic improvement without causing significant malabsorption. The objective of this study was to evaluate the results of this novel procedure for the control of type 2 diabetes mellitus (T2DM) in patients with a body mass index (BMI) of 24–32 kg/m 2.
Materials and Methods: Fifty-seven patients with T2DM who underwent LJISSA between February 2010 and May 2013 were recruited in this study. Data collected included fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), 1 h postprandial C peptide (1 h C-P), and glycosylated hemoglobin (HbA1c).
Results: Postoperatively, glycemic parameters (FBG and 2 h PBG, HbA1c and 1 h C-P) improved in all 57 patients. At 12 months, 34 patients had a remission of diabetes, and the remaining 23 patients showed a significantly decreased requirement for oral hypoglycemic agents. The patients with a BMI of 28–32 kg/m 2 had significant weight loss of between 7.8% and 20% (P < 0.05), whereas weight loss was not significant in those with a BMI of 24–28 kg/m 2. The group achieving remission had a higher BMI (28–32 kg/m 2), shorter duration of diabetes (<10 years), and higher stimulated C-P (>4 ng/mL). These three factors may be the predictors of diabetes resolution at 12 months.
Conclusion: LJISSA seems to be a promising procedure for the control of T2DM. A multicenter study with a larger number of patients and a longer follow-up period is needed to substantiate our preliminary findings.

Keywords: Gastric bypass, jejunoileal side-to-side anastomosis, metabolic surgery, type 2 diabetes mellitus


How to cite this article:
Li J, Xie G, Tian Q, Hu Y, Meng Q, Zhang M. Laparoscopic jejunoileal side-to-side anastomosis for the treatment of type 2 diabetes mellitus in Chinese patients with a body mass index of 24–32 kg/m2. J Can Res Ther 2016;12:5-10

How to cite this URL:
Li J, Xie G, Tian Q, Hu Y, Meng Q, Zhang M. Laparoscopic jejunoileal side-to-side anastomosis for the treatment of type 2 diabetes mellitus in Chinese patients with a body mass index of 24–32 kg/m2. J Can Res Ther [serial online] 2016 [cited 2018 May 22];12:5-10. Available from: http://www.cancerjournal.net/text.asp?2016/12/5/5/191618




 > Introduction Top


Type 2 diabetes mellitus (T2DM) is considered a pandemic or even a plague of the modern world. The global prevalence of diabetes among adults aged 20–79 years was estimated to be 6.4% in 2010, and it is projected to increase to 7.7% by 2030.[1] China has one of the largest diabetes mellitus populations in the world.[2] The total number of people in China with diabetes is projected to increase from 20.8 million in 2000 to 42.3 million in 2030.[3] This rise in diabetes prevalence has led to an intense search for some alternatives to the current treatment of T2DM and its consequences.

Currently, one of the most interesting alternatives is the surgical treatment of T2DM. It is well known that surgical procedures originally designed to treat morbid obesity may cause remission or significant improvement of T2DM. Traditionally, bariatric procedures have been reserved for patients with a body mass index (BMI) >40 kg/m 2, or >35 kg/m 2 for those with significant comorbidities. The remarkable impact of these operations on diabetes raises the possibility of surgical therapy for less obese patients with T2DM. Trials of Roux-en-Y gastric bypass (RYGB) in people with BMI <35 kg/m 2 have reported similar or even higher diabetes remission rates than those conducted in severely obese patients.[4],[5] Given that leaner individuals lose less total and percent body weight after RYGB than do more obese persons, the similarity in T2DM response hints that the operation might exert antidiabetic effects unrelated to weight loss.[6],[7],[8],[9] Consistent with this concept, experimental studies indicate that variations of RYGB improve T2DM in both obese and nonobese diabetic animals.[10],[11],[12],[13] Recent animal and clinical studies indicate that 50% to 60% of intestinal bypass or resection procedures can resolve diabetes in streptozotocin-induced diabetic rats [14] and restore glucose homeostasis in nonobese or mildly obese patients with T2DM.[15] Here, we present a new technique – called laparoscopic jejunoileal side-to-side anastomosis (LJISSA). The main goal was to offer all the known benefits of enhanced neuroendocrine response from faster stimulation of the distal bowel,[16],[17],[18],[19] without excluding or resecting any segments of the digestive tract. Jejunoileal side-to-side anastomosis is designed to allow partly undigested food into the distal ileum, and therefore would not significantly reduce intestinal absorption. This alteration of the intestinal tract aims to change the bowel's response to food intake and enhance incretin release, which ultimately has beneficial effects on pancreatic β-cell function and likely generates satiety signals.[16],[17],[18],[19] We, therefore, include selected nonobese and mildly obese patients with patients T2DM in our current study. We report the results of LJISSA treatment in 57 patients with T2DM, with a follow-up of 1 year.


 > Materials and Methods Top


The Scientific and Research Board of Southeast University and the Ethical Committee of Affiliated Xuzhou Hospital, Medical College of Southeast University of China, reviewed and approved the study protocol. All patients provided written informed consent after being informed thoroughly about the benefits and risks involved. Inclusion criteria for this study were as follows: age 18–65 years; BMI 24–32 kg/m 2, and poorly controlled T2DM as reflected by a glycosylated hemoglobin (HbA1c) level of ≥6.5%; a stimulated C-peptide (C-P) level of >1.5 ng/mL. Diagnosis of T2DM was based on the criteria of the American Diabetes Association and was considered valid if established by an endocrinologist or diabetes specialist.[20] The exclusion criteria were: type 1 diabetes mellitus; undetectable fasting C-P; positive urine ketones; pregnancy; coexisting severe hepatic, pulmonary, renal, cardiovascular, neurological, or psychiatric diseases; and obesity due to organic illness. LJISSA was performed in 57 patients between February 2010 and May 2013. All patients had been diagnosed with T2DM. Participants ranged in age from 29 to 60 years, had a duration of diabetes of 1 to 19 years, and preoperative BMI from 24 to 32 kg/m 2. Preoperatively, 39 (68.4%) patients required insulin or oral hypoglycemic agents (OHGAs), seven patients (12.3%) were receiving both insulin and OHGAs for glycemic control, and 11 (19.3%) other patients received no interventions for control. To evaluate the impact on LJISSA on patients with different mean BMI values, the patients were divided into two groups: Group A (24≤ BMI <28 kg/m 2, n = 27) and Group B (28≤ BMI <32 kg/m 2, n = 30). Before the operation, patients were assessed by a specialized team, including a surgeon, an endocrinologist, an anesthetist, a psychiatrist, and a dietician. Operative details recorded were operation time, duration of hospitalization, and complications, including early hemorrhage and bowel habit, until the last follow-up session. Follow-up visits were scheduled at 1 week and at 1, 3, 6, 9, and 12 months after surgery. Postoperative data collected included fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), 1 h postprandial C-P (1 h C-P), HbA1c, medication usage, and BMI. If patients were not taking antidiabetic medications and had a normal FBG of <7.0 mmol/L and a normal HbA1c of <6.5%, their condition was considered resolved. Those with an HbA1c of ≤7% despite no use of antidiabetic medications were considered to have achieved glycemic control. If the FBG decreased by >1.4 mmol/L or the HbA1c decreased by >1%, the patients' condition was considered to have improved.

Operative procedure

The operation was performed under general anesthesia with a standard four-port laparoscopic technique. A 10-mm infra-umbilical optical port was inserted under direct visualization. A 30° laparoscope was used in all cases. Additional ports were placed as follows: a left subcostal port 5-mm port, a left infer-axillary 12-mm port, and a right infer-axillary 5-mm port. The surgical procedure involved marking the jejunum at 45 cm from the ligament of Treitz and the ileum at 60 cm proximal to the ileocecal junction. Both places were anastomosed side by side with an Endo GIA stapler (Echelon Endopath, Tyco, USA) with a 45-mm white cartridge, and the stapler openings were closed by the Endo GIA stapler with 60-mm cartridges in two layers. The mesenteric gaps were closed with hemlock (Tyco, USA) to prevent internal herniation. [Figure 1] shows a diagrammatic representation of the procedure.
Figure 1: Diagrammatic representation of the procedure

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Postoperative follow-up

Postoperatively, diabetes medications were adjusted according to the plasma glucose levels. This operation is designed to shorten the transit time from jejunum to ileum and to change the bowel's response to food intake. Therefore, the patients started a liquid diet 1 day after surgery and continued it for 5–7 days, followed by a semisolid diet for another 7 days, and finally a solid diet, always in small quantities. They were asked to come for follow-up visits at 1, 3, 6, 9, and 12 months.

Statistical analysis

Microsoft Excel was used for data management. Statistical analyses were performed with SPSS 17.0 (http://www-01.ibm.com/software/analytics/spss/) statistical software. Data are expressed as mean (range) ± standard deviation. The Chi-square test or Fisher's exact test were used for categorical data. The unpaired t-test was used for parametric data. P < 0.05 was considered significant.


 > Results Top


A total of 57 patients underwent LJISSA (23 males and 34 females). Their baseline parameters are shown in [Table 1]. Postoperatively, 34 (59.6%) patients did not require insulin or OHGAs and maintained a normal FBG of <7.0 mmol/L and a normal HbA1c of <6.5%. More than 95.7% of the remaining 23 patients showed reductions in diabetes drug requirements. The mean operative time was 39 ± 13 min and the mean hospitalization time was 5 days (range 4–8 days). No intraoperative complications were noted, and none of the patients required conversion to open surgery. Postoperatively, there were no deaths, but 4 (7.0%) patients developed complications: One patient had an early hemorrhage at the jejunoileal anastomosis site, and the others had frequent loose stools. Postoperative follow-up data are shown in [Table 2]. In Group A, the change in mean BMI at 12 months compared to the mean preoperative BMI was significant (P < 0.01), while the mean BMI of Group B remained unchanged [Table 2]. LJISSA resulted in a marked improvement in the biochemical markers of diabetes [Table 3]. In the 57 patients, 1 h C-P levels were increased significantly from preoperative values at all postoperative assessments. Likewise, FBG and 2 h PBG decreased significantly from their preoperative values at all postoperative assessments. FBG and 2 h PBG were normalized in 15 (26.3%) and 9 (15.8%) patients, respectively, at 1 week, and in 39 (68.4%) and 30 (52.6%) patients, respectively, at 12 months. HbA1c was decreased significantly from preoperative values beginning at 1 month. About 34 (59.6%) patients achieved remission of T2DM, and the remaining 23 patients showed more than a 95.7% reduction in diabetes drug requirements and a 78.3% improvement in diabetes mellitus. We divided the patients into two groups according to three preoperative parameters: 28≤ BMI <32 kg/m 2 versus 24≤ BMI <28 kg/m 2, stimulated C-P (1 h postmeal) <4 ng/mL versus >4 ng/mL, and duration of diabetes ≤10 years versus >10 years. We found that the group that achieved remission after surgery seemed to have a greater BMI, greater stimulated C-P, and a shorter duration of diabetes [Table 4].
Table 1: Baseline data of the study group

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Table 2: Postoperative comparison of body weight and body mass index in Groups A and B

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Table 3: Postoperative metabolic parameters in 57 patients

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Table 4: Diabetes remission data in different subgroups of patients

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 > Discussion Top


All patients had considerable weight loss ranging from 5% to 18% of body weight. Diabetes control was good following surgery, with complete remission in 34 (59.6%) patients and more than a 95.7% reduction in diabetes drug requirements in the remaining 23 patients after 12 months. The remission persisted in all patients during the follow-up period. A trend was seen in lipid parameters, which decreased, although not to a statistically significant degree (data not shown). The definition of obesity according to BMI varies in different parts of the world. The WHO guidelines define obesity as >30 kg/m 2.[21] The cutoff value of BMI to define obesity in Asians is lower, and it is >28 kg/m 2 in China.[22] We selected a BMI cutoff value of ≥32.28 and 24 kg/m 2, respectively, for a diagnosis of morbid obesity, moderate obesity, and overweight in our study population, based on the available Asian data within different countries. In China, the BMI of the majority with T2DM ranges from 24 to 32 kg/m 2. Their islet function may be even worse according to the China Guideline for Type 2 diabetes. The purpose of jejunoileal side-to-side anastomosis is not to reduce gastrointestinal absorption but to reduce body weight to achieve the control of blood glucose, so we mainly selected moderate obesity and overweight patients for our study population with BMIs of 24–32 kg/m 2. Following surgery, there was significant reduction of weight from baseline in the range of 8.7%, 8.9%, and 9.6% at 3, 6, and 12 months, respectively, in the patients with a BMI of 28–32 kg/m 2. Correspondingly, a similar decline in BMI also was seen in this group, with reductions of 8.6%, 8.9%, and 9.6% at 3, 6, and 12 months, respectively. There was a slight reduction of weight and BMI in the patients with a BMI of 24–28 kg/m 2. A greater decline was seen in patients with higher BMIs. Overall, other studies evaluating the RYGB procedure have reported reductions in BMI in the range of 18% to 27%, and there were direct relationships between weight loss and preoperative BMI.[23],[24] Twelve months postsurgery, jejunoileal side-to-side anastomosis resulted in smaller reductions in BMI compared to RYGB. However, there was a remarkable glycemic improvement in all the 57 patients. The improvements in glycemic parameters (FBG, PBG, HbA1c, and 1 h post meal C-P) were statistically significant during follow-up at all the assessments. Postoperative glycemic improvement was disproportionately greater than weight loss, pointing to the independent benefits of the metabolic surgery. Based on this and available literature,[25],[26] patients with BMI <28 kg/m 2 were also subjected to this procedure and showed improvement in glycemic control with substantial reductions in antidiabetic agent requirements. There was a significant reduction of weight from the baseline of 9.6% at 12 months in the patients with BMI of 28–32 kg/m 2, but only a slight reduction of weight and BMI in the patients with BMI of 24–28 kg/m 2. In subgroups of BMI 24≤ BMI <28 kg/m 2 versus 28≤ BMI <32 kg/m 2, 55.6% versus 63.3% of patients had complete remission of diabetes, and the group that achieved higher remission 12 months after operation seemed also to have a higher weight loss. It is possible to explain the better improvement in the group with higher BMI because of the greater weight loss. In our center, some patients with T2DM with a BMI of 28≤ BMI <32 kg/m 2 and BMI ≥32 kg/m 2 chose duodenal-jejunal bypass and gastric bypass. At 1 year, there were significant reductions of weight from baseline of 13.5% and 18.9%, respectively, and 64.9% versus 82.3% of patients, respectively, had complete remission of diabetes, which is comparable to the results in the present study.

The changes in biochemical glycemic parameter in our patients confirm that LJISSA is effective in nonobese diabetic patients with BMI of 24–28 kg/m 2 to improve their glycemic and metabolic parameters. The key strengths of this study are the safety and efficacy of the surgery in treating patients with T2DM with a lower BMI, and the possibility of other achievements beyond glycemic control, which were suitable for our Chinese population. Possible mechanisms to explain the benefits of this procedure in nonobese patients could be as follows: earlier exposure of food to ileum, leading to a better incretin response [27] and ileal brake food partly entering into the ileum modulates gastric and intestinal motility to reduce food intake and absorption.[28] The surgical technique used in this study is designed essentially for diabetes control and utilizes hindgut mechanisms. LJISSA diverts partly undigested food into the ileum and possibly reduces ghrelin, a potent orexigenic substance that contributes significantly toward impaired glucose homeostasis.[29],[30],[31] Glucagon-like peptide 1 (GLP-1), the incretin responsible for the first phase of insulin secretion, is defective in T2DM. In jejunoileal side-to-side anastomosis, rapid stimulation of the ileal segment by ingested food possibly leads to augmented GLP-1 secretion.[32],[33],[34] Postprandial glucose homeostasis is determined not only by the stimulation of insulin secretion and suppression of hepatic glucose production, but also by the velocity of gastric emptying. GLP-1 also influences glucose metabolism by inhibiting glucagon secretion, decreasing hepatic gluconeogenesis, delaying gastric emptying, promoting satiety, suppressing appetite, and stimulating glycogenesis.

Higher remission rates of diabetes were observed in the group of patients with a higher BMI, shorter duration of diabetes (≤10 years), and higher stimulated C-P levels (>4 ng/mL). Measurement of stimulated C-P levels is a commonly accepted tool for assessing insulin secretion and function of the β-cell.[35],[36],[37] Previous studies have found an association between a higher success rate for bariatric surgery and a shorter duration of T2DM or a shorter duration of medication use and higher stimulated C-P.[38],[39] However, the accuracy of these factors as predictors of outcome in individual patients is limited. We hypothesize that the measurement of preoperative stimulated C-P levels and shorter duration of T2DM may have predictive power because it is a tool for assessing β-cell function. Multicenter studies on a larger number of patients with a longer follow-up period would strengthen our observations.

In nonobese subjects with T2DM, defective early insulin secretion after an oral glucose load is a key factor leading to hyperglycemia. This defective β-cell function is associated with a reduced early GLP-1 response. Metabolic surgery (LJISSA) corrects this defect,[25] and hence it is also beneficial in nonobese diabetic patients with BMI <28 kg/m 2. In this study, we investigated the confounding glucose-lowering effect induced at 7 days after surgery, independent of changes in the body weight. The underlying mechanisms responsible for the glucose-lowering effect induced by LJISSA remain to be completely explained. Previous studies have found that the redirection and enhancement of nutrient flow into the jejunum or ileum that is triggered shortly after a meal mediates the rapid glucose-lowering effect induced by proximal intestinal bypass operation, which is achieved through a reduction in endogenous glucose production.[40],[41],[42] Other studies have found that bile diversion seems to inhibit interdigestive and postprandial upper gut contractions in association with an increase of plasma peptide YY. Pancreatic juice was considered to play a role in the secretion of gastric inhibitory polypeptide.[43]

In the 57 patients who underwent LJISSA, there was a significant reduction of weight from baseline (9.6% at 1 year), in the patients with BMI of 28–32 kg/m 2, but a smaller reduction of weight and BMI in the patients with BMI of 24–28 kg/m 2. We found a very low rate of complications and no mortality in our study group. Thus, LJISSA appears to be a safe procedure. The average operating time (30–50 min) was much less than that required for RYGB and biliopancreatic diversion. Iron deficiency was not observed during the 1-year follow-up. Long-term data are needed to further establish the efficacy of this procedure.


 > Conclusion Top


This surgery based on the principle of neuroendocrine brake appears to be safe and a potentially effective option in the management of patients with T2DM. Patients with a higher BMI, shorter duration of diabetes, and higher stimulated C-P values should respond better. Further long-term data from a larger number of patients are necessary to define the role of this novel surgery in T2DM and related metabolic abnormalities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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