Short-term impact of bariatric surgery on the dietary intake of patients with type 2 diabetes.

BACKGROUND: The prevalence of overweight and obesity and an unhealthy diet and lifestyle are the key causes of rising diabetes burden in India. Bariatric surgery is gaining popularity in India as a favored approach to manage obesity and its accompanying comorbidities. Despite this, there is a scarcity of Indian studies evaluating dietary intake. Our goal was to analyse the dietary intake of Indian patients with type 2 diabetes mellitus (T2DM) who have undergone laparoscopic sleeve gastrectomy (LSG) or duodeno-jejunal bypass with sleeve gastrectomy (DJB-SG) or surgeries. METHODS: The longitudinal observational study included 64 T2DM patients (32 in each procedure) enrolled through purposive sampling. The patients underwent surgery (LSG or DJB-SG procedure) between January 2017 and July 2019. Dietary data was collected at baseline and postsurgery (12 months) using a 24-h dietary recall method for 2 days (one working and one holiday). RESULTS: The total sample consisted of 27 (42.2%) females and 37 (57.8%) males. The mean age was 46.8 years. At 12 months, the follow-up for the LSG and DJB-SG procedures was 100% and 78%, respectively. In the short term, a significant reduction was seen in weight, body mass index and haemoglobin A1C (HbA1C) in both surgical groups. The two procedures were comparable with respect to weight loss but improvement in glycaemia was higher in the DJB-SG group. The dietary intake (food groups and nutrients) was similar in the two surgical groups at baseline and 12 months postsurgery. Dietary intake assessment showed significant reduction in calorie dense foods (cereals, roots and tubers, fats and oils, table sugar, and biscuits) in both surgical groups. Among nutrients, intake of energy, fats, carbohydrates, dietary fibre, thiamine, riboflavin, niacin, folate and iron were reduced significantly in both procedures. Vitamin D (84.4% patients in LSG group and 81.3% patients in DJB-SG) and iron (62.5% patients in LSG group and 68.8% patients in DJB-SG) were commonly prevalent nutritional deficiencies at baseline and were significantly reduced at 12 months. CONCLUSIONS: In the short term, bariatric surgery resulted in weight loss and improvement in glycaemia. Bariatric surgery does significantly affect dietary intake leading to nutritional deficiencies. Therefore, patients should be recommended vitamin and mineral supplements and regular patient education and counselling by a trained bariatric dietitian to prevent nutritional deficiencies and maintain nutritional status.

Duodenal-Jejunal Bypass Restores Sweet Taste Receptor-Mediated Glucose Sensing and Absorption in Diabetic Rats.

Aim: The aim of the study is to identify the regulatory role of intestinal sweet taste receptors (STRs) and glucose transporters (SGLT1, GLUT2) and gut peptide secretion in duodenal-jejunal bypass (DJB)-ameliorated glycemic control in Type 2 diabetes. Materials and Methods: DJB and sham surgeries were performed in streptozotocin-induced diabetic male rats. The blood GLP-1 and GLP-2 levels were evaluated under feeding and fasting conditions. The expression of STRs (T1R2, T1R3), sweet taste signaling effector (Gα-gustducin), SGLT1, and GLUT2 was detected in the intestinal alimentary limb (A limb), biliopancreatic limb (BP limb), and common limb (C limb). The effects of STR inhibition on glucose control were measured with lactisole. Results: Glucose tolerance was improved in DJB-operated rats compared with the sham group, similar to that of normal control rats, without significant differences in food intake and body weight. The plasma GLP-1 levels of DJB rats were increased under diet-fed condition, and GLP-2 levels were increased after fasting. The villus height and crypt depth were significantly increased in the A limb of DJB-operated rats. In addition, GLP-1 expression was restored in enterocytes. The expression of T1R2, Gα-gustducin, and SGLT1 was elevated in the A limb after DJB, while GLUT2 was downregulated in the A, BP, and C limbs. The localization of GLUT2 was normalized in the three intestinal limbs after DJB. However, the beneficial effects of DJB on glucose control were abolished in the presence of lactisole in vivo. Conclusion: DJB ameliorates glycemic control probably by restoring STR-mediated glucose sensing and absorption with the responses of GLP-1 and GLP-2 to carbohydrate.

Role of Proximal Intestinal Glucose Sensing and Metabolism in the Blood Glucose Control in Type 2 Diabetic Rats After Duodenal Jejunal Bypass Surgery.

BACKGROUND: Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery. METHODS: A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR. RESULTS: Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats. CONCLUSION: Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB.

Roux-En-Y Gastric Bypass Versus Sleeve Gastrectomy Plus Procedures for Treatment of Morbid Obesity: Systematic Review and Meta-Analysis.

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed bariatric procedures globally, but both techniques have shortcomings. Several modifications of SG (SG plus procedures) have been developed, but the efficacy of the different procedures has not been completely elucidated. In this meta-analysis, we aimed to evaluate the efficacy and safety of SG plus procedures. Out of the initially identified 2357 studies, thirteen were selected for this meta-analysis: two studies on banded sleeve gastrectomy (BSG), four studies on sleeve gastrectomy plus duodenal-jejunal bypass (SG + DJB) or sleeve gastrectomy with loop duodenal-jejunal bypass (SADJB), two studies on sleeve gastrectomy with jejunal-jejunal bypass (SG + JJB), four studies on single anastomosis duodenal-ileal switch (SADI-S), and one study on stomach intestinal pylorus-sparing surgery (SIPS). SADI-S procedure was found to achieve significantly greater percentage of excess weight loss than the RYGB. SG + DJB and SADJB achieved greater weight loss than the RYGB. Major complications were fewer with SG + JJB than with RYGB, but the difference was not significant. Overall, SG plus procedures appear to achieve better weight loss and cause fewer complications than RYGB.

New Anchoring Mechanism and Design of an Endoluminal Duodeno-Jejunal Bypass Liner for Treatment of Obesity: a Pilot Animal Trial.

OBJECTIVE: Complications of bleeding, liver abscess and movement have been associated with previous duodeno-jejunal bypass liner (DJBL) applications in the past. A new anchoring system and design of a DJBL is presented as a pilot study. METHOD: A newly designed DJBL device was inserted in 2 pigs and observed over 2 months. RESULTS: The newly designed device was anchored and monitored for 1 month in 1 of 2 pigs, the other being passed early. Effectiveness and safety have been shown. CONCLUSION: The results of this pilot study warrant further investigation of the modified DJBL setup, which may help solve standing issues associated with the clinical use of a DJB liner.

Early gastric cancer successfully treated by endoscopic submucosal resection 1 year after laparoscopic sleeve gastrectomy with duodenal-jejunal bypass.

This case involved a 64-year-old female patient with a BMI of 35.3 kg/m2 and poorly controlled type 2 diabetes mellitus. Preoperative upper gastrointestinal endoscopy revealed chronic, atrophic gastritis. Helicobacter pylori antibody was negative. The patient underwent laparoscopic sleeve gastrectomy with duodenal-jejunal bypass as a metabolic surgery to treat obesity and type 2 diabetes mellitus. At 1 year postoperatively, routine endoscopy detected a flat elevated lesion at the distal gastric sleeve, near the posterior wall of the antrum; biopsy revealed adenocarcinoma. Endoscopic submucosal resection was performed without complication. This case shows the advantage of laparoscopic sleeve gastrectomy with duodenal-jejunal bypass in screening the excluded stomach as compared to laparoscopic Roux-en-Y gastric bypass. Therefore, laparoscopic sleeve gastrectomy with duodenal-jejunal bypass can be a viable alternative to laparoscopic Roux-en-Y gastric bypass for regions where gastric cancer is endemic.

Duodenojejunal Bypass Plus Sleeve Gastrectomy Reduces Infiltration of Macrophages and Secretion of TNF-α in the Visceral White Adipose Tissue of Goto-Kakizaki Rats.

BACKGROUND: Current studies indicate that inflammation of white adipose tissue (WAT) is a pathogenic characteristic of insulin resistance. However, the significance of visceral WAT inflammation after bariatric surgery remains unclear. METHODS: Duodenojejunal bypass plus sleeve gastrectomy (DJB-SG) was performed on Goto-Kakisaki rats. Weight, fasting blood glucose (FBG), and homeostatic model assessment of insulin resistance (HOMA-IR) in the DJB-SG group were compared to those in a sham surgery (SHAM) group every 2 weeks. The results of an oral glucose tolerance test (OGTT) and the volume of visceral adipose tissue (Visc.Fat) were compared before and 8 weeks postsurgery. Eight weeks after surgery, the rats were sacrificed and visceral WAT collected from the greater omentum. Tumor necrosis factor-α (TNF-α) and cluster of differentiation 68 (CD68) expression in the WAT were evaluated in paraffin-embedded sections by immunohistochemistry. RESULTS: Compared with the SHAM group, the DJB-SG group demonstrated a significant reduction in weight, FBG, and HOMA-IR (P < 0.05), with elevation of insulin levels (P < 0.05) from 4 weeks after surgery. OGTT and the quantity of Visc.Fat were significantly reduced (P < 0.05) 8 weeks after surgery. Moreover, the expression of TNF-α and CD68 in the visceral white adipose tissue was significantly lower 8 weeks after surgery (P < 0.05). CONCLUSIONS: The DJB-SG model established in Goto-Kakisaki rats achieved anticipated efficacy. Reduced TNF-α-related inflammation in visceral WAT may result in improved insulin resistance.

A rare case of idiopathic congenital megaduodenum in adult misinterpreted during childhood: case report and literature review.

Intestinal malformations are common disorders in newborn and favorable outcomes have been reported for such conditions. Although, if the patient is treated in a not experienced center, misinterpretation of the clinical and radiological findings may lead to errors in treatment and possible complications in adulthood. We report a case of a congenital megaduodenum which was misinterpreted as an intestinal malrotation resulting in late complications. The patient underwent a successful surgical resection of the duodenum with improvement of his clinical symptoms and nutritional status. This case report emphasizes the importance of considering megaduodenum in the differential diagnosis of patients with feeding impairment, even during adulthood. Early diagnosis and treatment may improve patients' outcome and reduce morbidity.

The Effects of Laparoscopic Sleeve Gastrectomy with Duodenojejunal Bypass on Japanese Patients with BMI < 35 kg/m2 on Type 2 Diabetes Mellitus and the Prediction of Successful Glycemic Control.

BACKGROUND: Laparoscopic sleeve gastrectomy with duodenojejunal bypass (LSG-DJB) is a combination of sleeve gastrectomy and proximal intestinal bypass through duodenal exclusion. This technique has shown excellent weight loss and anti-diabetic effects in severely obese patients. In this retrospective study, we examined the clinical effects of LSG-DJB on mildly obese patients (body mass index (BMI) < 35 kg/m2) with type 2 diabetes mellitus (T2DM) and analyzed factors contributing to the successful postoperative glycemic control. METHODS: Seventy-two consecutive Japanese patients with T2DM with a BMI of < 35 kg/m2 who underwent LSG-DJB in a single institution from September 2007 to March 2015 were included for the study. Weight loss, safety, and the impact on T2DM and metabolic syndrome were examined at 1 year after surgery when weight loss reaches an expected plateau. In addition, pre- and postoperative factors between those who achieved diabetes remission (remitters) and non-remitters were compared. RESULTS: The follow-up rate at 1 year after surgery was 93%. The mean percent total weight loss (%TWL) was 31.6 ± 8.8%, and the mean glycosylated hemoglobin (HbA1c) dropped from 8.9 ± 1.5 to 6.4 ± 1.0%. There were four early- and seven late-severe complications (grade III-A or more based on the Clavien-Dindo classification), which account for the 1-year morbidity rate of 15%. There was no mortality. The complete (HbA1c of < 6% without diabetes medication) and partial (HbA1c of < 6.5% without diabetes medication) remission of T2DM was achieved in 31 and 49% of the patients, respectively. Positive impacts were also observed on hypertension and dyslipidemia. Consequently, the ratio of those who achieved the composite endpoint (HbA1c of < 7%, low-density lipoprotein cholesterol < 100 mg/dL, systolic blood pressure < 130 mmHg) significantly increased from 4.2 to 22% (p = 0.003). Duration of T2DM and preoperative use of anti-hypertensive drugs were independent predictors of diabetes remission. Patients with a higher ABCD score were also at a higher rate of success in T2DM remission. CONCLUSIONS: LSG-DJB for T2DM patients with a BMI of < 35 kg/m2 is a feasible and effective surgical method in achieving moderate weight loss and excellent improvement of glycemic control, metabolic syndrome, and cardiovascular risk although the T2DM remission rate was lower compared with severely obese individuals. Proper patient selection for candidates of the procedure is imperative to effectively predict poor responders.

Duodenal-jejunal bypass attenuates progressive failure of pancreatic islets in streptozotocin-induced diabetic rats.

BACKGROUND: Preservation of pancreatic beta cell function has been increasingly appealing in the treatment of type 2 diabetes. Evidence is still limited on how bariatric surgery affects pancreatic beta cell apoptosis. SETTING: University medical center. OBJECTIVE: The study aimed to investigate the effect of a major component of Roux-en-Y gastric bypass, duodenal-jejunal bypass, on protecting pancreatic beta cells from progressive loss. METHODS: Forty-five normal Sprague-Dawley rats were randomly assigned into 3 groups: duodenal-jejunal bypass (DJB) group (n = 16) and sham (S) group (n = 17), based upon the procedure received, and a control (C) group (n = 12) without any procedure performed, to eliminate potential traumatic effects from surgery. Ten days after surgery, streptozotocin (STZ, 45 mg/kg weight) was injected intraperitoneally into each animal, including the control animals, to selectively induce pancreatic beta cell apoptosis. Weight, food intake, plasma glucose level, and the results of an oral glucose tolerance test were measured before surgery, pre-STZ injection, and up to 4 weeks after STZ injection. Plasma insulin and glucagon-like peptide-1 levels were also assayed during oral glucose tolerance test. At the end, pancreatic tissues were sliced and stained for beta cell analysis. RESULTS: There were no significant differences in weight among all groups at any time points measured, despite rats in the S and C groups consuming more food than those in the DJB group as measured on day 10 (P<.05) and day 20 (P<.01) after STZ injection. Animals undergoing DJB did not experience symptoms typical of uncompensated diabetes, including hyperphagia and progressive weight loss. After STZ injection, fasting plasma glucose levels in the DJB group were significantly lower than those in the C and S groups (P<.001). When challenged by glucose load, DJB rats also had a better glycemic excursion (P<.01) and incretin response compared with C and S rats (P<.05). In addition, pancreatic beta cell size and mass was better preserved in DJB rats (P< .001). CONCLUSION: DJB is able to protect pancreatic beta cells from apoptosis, which leads to better glycemic control and delayed onset of diabetes. These results imply the necessity of including a DJB component when designing bariatric procedure to achieve a better long-term outcome.

Duodenal long noncoding RNAs are associated with glycemic control after bariatric surgery in high-fat diet-induced diabetic mice.

BACKGROUND: The duodenum plays a role in the mechanism of type 2 diabetes remission after bariatric surgery. Roux-en-Y gastric bypass (RYGB) may change gene expression in the duodenum and metabolism. Long noncoding RNAs (lncRNAs) constitute a novel class of RNAs that regulate gene expression. Little is known about how duodenal lncRNAs respond to RYGB. Logically, studies on the changes of duodenal lncRNAs potentially can lead to an understanding of the mechanisms of bariatric surgery, as well as discovery of antidiabetic drug targets and biomarkers predicting postoperative outcome. OBJECTIVES: To investigate the expression signature of duodenal lncRNAs associated with glycemic improvement by duodenal-jejunal bypass (DJB), a component of RYGB, on a genome-wide scale in high-fat diet-induced diabetic mice. SETTING: University medical center. METHODS: High fat diet-induced diabetic mice were randomized into 2 groups receiving either the DJB or a sham procedure. Microarray was applied to screen the differentially expressed lncRNAs and messenger RNAs (mRNAs) in the duodenum between the DJB and sham groups, and the result was validated by quantitative real-time polymerase chain reaction in another cohort of animals. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the potential lncRNA functions. Based on Pearson correlation analysis, the lncRNA-mRNA and lncRNA-transcription factor (TF) interaction networks were constructed to identify and rank core regulatory lncRNAs and transcription factors. RESULTS: A total of 301 lncRNAs, including 232 that were upregulated and 69 downregulated (fold change≥2.0), were differentially expressed in the duodenum between the DJB and sham groups. GO enrichment indicated that these lncRNA-coexpressed mRNAs were correlated with biological processes including cell proliferation, digestion, and catabolic and biosynthetic processes. KEGG pathway analysis revealed that in addition to the digestion and absorption signaling pathways, pancreatic secretion- and inflammatory process-related signaling pathways were mostly enriched in the DJB group. In addition, the lncRNA-mRNA interaction network combined with GO and KEGG pathway analysis suggested that as a top-ranked gene, NONMMUG021726 may play an important role in the mechanism of type 2 diabetes remission after DJB. CONCLUSION: DJB leads to drastic changes in lncRNA and mRNA expressions in the duodenum. The majority of top-ranked lncRNAs and mRNAs have roles in pancreatic secretion and inflammatory processes, implying that bypass of the duodenum may initiate insulin secretion and attenuate inflammation. In addition, modulators of such lncRNAs, most likely NONMMUG021726, have potential to become therapeutic targets or biomarkers for prediction of the outcomes of bariatric surgery.

Duodenal-Jejunal Bypass Surgery Reverses Diabetic Phenotype and Reduces Obesity in db/db Mice.

Type 2 diabetes mellitus (T2DM), a complex metabolic disorder typically accompanying weight gain, is associated with progressive ß-cell failure and insulin resistance. Bariatric surgery ameliorates glucose tolerance and provides a near-perfect treatment. Duodenal-jejunal bypass (DJB) is an experimental procedure and has been studied in several rat models, but its influence in db/db mice, a transgenic model of T2DM, remains unclear. To investigate the effectiveness of DJB in db/db mice, we performed the surgery and evaluated metabolism improvement. Results showed that mice in DJB group weighed remarkably less than sham group two weeks after surgery. Compared to the preoperative level, postoperative fasting blood glucose (FBG) was dramatically reduced. Statistical analysis revealed that changes in body weight and FBG were significantly correlated. Besides, DJB surgery altered plasma insulin level with approximate 40% reduction. Thus, for the first time we proved that DJB can achieve rapid therapeutic effect in transgenic db/db mice with severe T2DM as well as obesity. In addition, decreased insulin level reflected better insulin sensitivity induced by DJB. In conclusion, our study demonstrates that DJB surgery may be a potentially effective way to treat obesity-associated T2DM.

Laparoscopic Sleeve Gastrectomy with Duodenojejunal Bypass for Type 2 Diabetes Mellitus.

BACKGROUND: Laparoscopic sleeve gastrectomy with duodenojejunal bypass (LSG-DJB), which has been positioned as a novel bariatric procedure, is the combination of vertical sleeve gastrectomy and proximal intestinal bypass and is theoretically expected to have strong anti-diabetic effect. Also, preserving the pylorus, a physiological valve, leads to less occurrence of dumping syndrome and anastomotic stenosis which are often problematic after laparoscopic Roux-en-Y gastric bypass (LRYGB), a gold standard. The purpose of this study was to investigate the clinical effects of LSG-DJB on obese patients with type 2 diabetes mellitus (T2DM). METHODS: Consecutive 75 obese patients (female 44/male 31) associated with T2DM who underwent LSG-DJB and were followed up for at least 1 year were analyzed. The mean age was 45.5 ± 8.6 years, and the mean preoperative body weight (BW) and body mass index (BMI) were 108.4 ± 21.4 kg and 39.6 ± 7.3 kg/m(2), respectively. The mean hemoglobin A1c (HbA1c) at the first visit was 9.0 ± 1.9 %, and the duration of T2DM from diagnosis was 7.2 ± 6.2 years. Thirty-six out of the 75 patients (48 %) were treated with insulin preoperatively. All patients were evaluated and managed under a strict multidisciplinary team approach. The follow-up rate at 1 year was 89 %. RESULTS: At 1 year, the mean BW and BMI significantly dropped to 74.6 ± 16.9 kg and 27.5 ± 5.7 kg/m(2), respectively. The mean percent of excess weight loss (%EWL) and percent of total body weight loss (%TWL) were 99.4 ± 42.4 and 31.6 ± 8.8 %, respectively. Consequently, 68.7 % of the patients achieved HbA1c less than 6 %, and 82.1 % of them achieved HbA1c less than 6.5 % without diabetes medications. Glycemic control of HbA1c less than 7 % was achieved in 91.0 % of the patients. The percentage of patients who satisfied the American Diabetes Association (ADA)-defined composite endpoints for cardiovascular disease (CVD) risk factor control increased from 0 % (at baseline) to 31 % (at 1 year). A meal tolerance test revealed significant reduction of glucose area under the curve (AUC) and increase of insulin AUC postoperatively. CONCLUSIONS: LSG-DJB for obese patients with T2DM has strong anti-diabetic effect in the short-term; however, a larger number of patients with a longer follow-up period are needed for definitive conclusions.

Duodenal-jejunal bypass for the treatment of type 2 diabetes in Chinese patients with an average body mass index<24 kg/m2.

BACKGROUND: It is frequently reported that bariatric surgery often leads to resolution of type 2 diabetes mellitus (T2 DM). Limited experience with duodenal-jejunal bypass (DJB) for the treatment of T2 DM has shown controversial results. We present the first study of DJB for T2 DM patients in China. The objective of this study was to evaluate the effects of DJB in nonobese Chinese patients with T2 DM. METHODS: From March 2009 to March 2011, a total of 10 T2 DM patients with an average body mass index (BMI) of 23.8 ± 1.2 kg/m(2) were enrolled in the study. DJB was performed in all patients. BMI and glycometabolic parameters were collected at baseline and 1, 3, 6, 12, and 24 months postoperatively. Remission of T2 DM was defined as a glycosylated hemoglobin (HbA1c) level of<7% without diabetic medication. RESULTS: Remission of T2 DM was observed in 1 (10%) of 10 T2 DM patients at 6 months. Without increasing antihyperglycemic agents, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose, and HbA1c decreased significantly at each postoperative time point, compared with the preoperative baseline. BMI statistically decreased at 1 and 3 months, but did not reach statistical significance at 6, 12, and 24 months. CONCLUSIONS: DJB can improve glycemic control in nonobese T2 DM patients without significant weight loss but may not be effective enough to induce remission of T2 DM in nonobese Chinese patients. A larger sample size and more constrictive inclusion criteria may be required for better evaluation.