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      Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels

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          Abstract

          Background and study aims: Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this observational study, we evaluated improvement of glycemic control and weight loss in the course of the treatment (0 – 24 weeks after DJBL implantation) and analyzed accompanying gut hormone responses.

          Patients and methods: 12 obese individuals with type 2 diabetes were selected for DJBL implantation. Body weight, fat mass, and fasting plasma levels of glucose, insulin, C-peptide, and glycated hemoglobin (HbA1c), were analyzed at 0, 1, 4 and 24 weeks post-implant. Fasting ghrelin, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP-1) were determined at 0, 1 and 4 weeks post-implant.

          Results: Besides significant weight loss, fat mass, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index were also significantly decreased after DJBL implantation and a 42 % reduction was found in diabetes medication ( P < 0.05). The fasting GLP-1 response in the first 4 weeks post-implant was significantly correlated with the fasting insulin and HOMA-IR response. Fasting ghrelin was found to be significantly elevated, in contrast to the decrease in ghrelin that is found after RYGB surgery.

          Conclusions: DJBL implantation provoked significant weight loss, a decrease in fat mass, and an early remission of type 2 diabetes, comparable to results seen after RYGB surgery. Gut hormone analyses revealed a potential role of fasting GLP-1 in early remission of type 2 diabetes. Interestingly, the DJBL-induced elevation of ghrelin contradicts the suggested role of reduced ghrelin levels after RYGB in improvement of glycemic control.

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          Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.

          Sarah E Wild, Gojka Roglic, Anders Green … (2004)
          The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030. Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations' population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries. The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age. These findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
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            The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

            Francesco Rubino, Antonello Forgione, David E Cummings … (2006)
            Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.
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              Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.

              Philip Schauer, Bartolomé Burguera, Sayeed Ikramuddin … (2003)
              To evaluate pre- and postoperative clinical parameters associated with improvement of diabetes up to 4 years after laparoscopic Roux-en-Y gastric bypass (LRYGBP) in patients with type 2 diabetes mellitus (T2DM). The surgical treatment of morbid obesity leads to dramatic improvement in the comorbidity status of most patients with T2DM. However, little is known concerning what preoperative clinical factors are associated with postoperative long-term improvement in diabetes in the morbidly obese patient with diabetes. METHODS We evaluated pre- and postoperative data, including demographics, duration of diabetes, metabolic parameters, and clinical outcomes, in all patients with impaired fasting glucose (IFG) and type T2DM undergoing LRYGBP from July 1997 to May 2002. During this 5-year period, 1160 patients underwent LRYGBP and 240 (21%) had IFG or T2DM. Follow up was possible in 191 of 240 patients (80%). There were 144 females (75%) with a mean preoperative age of 48 years (range, 26-67 years). After surgery, weight and body mass index decreased from 308 lbs and 50.1 kg/m2 to 211 lbs and 34 kg/m2 for a mean weight loss of 97 lbs and mean excess weight loss of 60%. Fasting plasma glucose and glycosylated hemoglobin concentrations returned to normal levels (83%) or markedly improved (17%) in all patients. A significant reduction in use of oral antidiabetic agents (80%) and insulin (79%) followed surgical treatment. Patients with the shortest duration (<5 years), the mildest form of T2DM (diet controlled), and the greatest weight loss after surgery were most likely to achieve complete resolution of T2DM. LRYGBP resulted in significant weight loss (60% percent of excess body weight loss) and resolution (83%) of T2DM. Patients with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery, suggesting that early surgical intervention is warranted to increase the likelihood of rendering patients euglycemic.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Endosc Int Open
                Journal ID (iso-abbrev): Endosc Int Open
                Journal ID (publisher-id): Endoscopy International Open
                Title: Endoscopy International Open
                Publisher: © Georg Thieme Verlag KG (Stuttgart · New York )
                ISSN (Print): 2364-3722
                ISSN (Electronic): 2196-9736
                Publication date (Print): March 2014
                Publication date (Electronic): 07 March 2014
                Volume: 2
                Issue: 1
                Pages: E21-E27
                Affiliations
                [1 ]Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
                [2 ]Department of General Surgery, Rijnstate, Arnhem, The Netherlands
                [3 ]Department of Gastroenterology, Rijnstate, Arnhem, The Netherlands
                Author notes
                Corresponding author Nicole de Wit, PhD Human Nutrition,Wageningen University Bomenweg 2Wageningen 6703 HDThe Netherlands nicole.dewit@ 123456wur.nl
                Article
                DOI: 10.1055/s-0034-1365222
                PMC ID: 4423279
                PubMed ID: 26134609
                SO-VID: c395274a-069b-4166-b81a-1560567e3c48
                Copyright © © Thieme Medical Publishers
                History
                Date received : 20 August 2013
                Date accepted : 08 January 2014
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                Subject: Article

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