Effect of Duodenal–Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes

Rubino, Francesco; Marescaux, Jacques

doi:10.1097/01.sla.0000102989.54824.fc

Cited by 589 publications

(412 citation statements)

References 46 publications

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“…With regard to this, it should be noted that while several surgical techniques leave the duodenum in place, duodenal transit is excluded in the standard BPD. Indeed, exclusion of the duodenum from alimentary transit has been shown to be crucial for the reversion of diabetes in Goto-Kakyzaky rats [23]. Thus, some hitherto unknown substance with insulin desensitising properties would be produced in the duodenal tract of severely obese subjects upon nutrient passage; shunting food downstream to the duodenum would result in a fall in the release of such substance, with a consequent brisk improvement in insulin action.…”

Section: Discussionmentioning

confidence: 99%

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

et al. 2006

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Aims/hypothesis The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing biliopancreatic diversion (BPD). Subjects and methods We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52± 7 kg/m 2 , mean±SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery. Results BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341±79 ml min −1 m −2 , post-BPD 511±57 ml min −1 m −2 , lean 478±49 ml min −1 m −2 ). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min −1 m −2 l mmol −1 , median [interquartile range]) compared with lean subjects (82 [98]; p≤0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r 2 =0.67, partial r=−0.76 and −0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement. Conclusions/interpretation Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

et al. 2006

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“…He developed a gastric-sparing variant of RYGB known as the duodenal-jejunal bypass (DJB), in which the stomach is left intact, but an intestinal bypass is created that excludes from digestive continuity the same modest segment of proximal small intestine as is excluded in a standard RYGB. 19 In Goto-Kakizaki rats, a nonobese model of polygenic T2DM, this operation improved diabetesFrapidly, durably and impressivelyFeven though it caused no reduction in food intake or body weight compared with sham-operated controls. Similar observations have subsequently been made with independent investigations of non-obese diabetic Goto-Kakizaki rats 20,21 and obese diabetic Zucker rats.…”

Section: The Upper Intestinal Hypothesismentioning

confidence: 99%

“…Consistent with this concept, experimental studies indicate that variations of RYGB improve T2DM not only in obese but also in nonobese diabetic animals. [18][19][20][21] Despite a growing interest in using RYGB to treat T2DM, even among less obese or non-obese patients, the underlying mechanisms of action of this procedure have not been fully evaluated. As gastrointestinal (GI) surgery appears to eliminate T2DM more effectively, rapidly and durably than any existing non-surgical method, and because the usage of bariatric surgery is rapidly increasing worldwide, elucidating the mechanisms by which these operations improve glycemia is an important research priority.…”

Section: Remission Of Diabetes After Rygbmentioning

confidence: 99%

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weightindependent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic b-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides (for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment. Keywords: diabetes; gastric bypass; bariatric surgery; ghrelin; GLP-1 Bariatric operations traditionally have been thought to cause weight loss through gastric restriction and/or intestinal malabsorption. Restrictive operations such as adjustable gastric banding (AGB) create a small pouch in the proximal stomach to reduce functional gastric capacity and retard gastric emptying. Malabsorptive procedures such as biliopancreatic diversion (BPD) leave much of the stomach intact but divert ingested food from the stomach to the ileum; thus, only a small segment of the distal bowel can absorb nutrients. The typical proximal Roux-en-Y gastric bypass (RYGB) creates gastric restriction and also causes food to bypass most of the stomach and a short segment of the proximal intestine, primarily the duodenum, leaving enough intact small bowel in digestive continuity to avoid clinically significant malabsorption. RYGB causes weight loss through gastric restriction and additional mechanisms involving changes in gut hormones and other processes under active investigation. 1-14 RYGB and BPD produce the highest and most rapid rates of remission of type 2 diabetes mellitus (T2DM). Remission of diabetes after RYGBAlthough bariatric surgery was designed to facilitate weight loss, anecdotal reports of rapid postoperative remission of T2DM emerged as early as the 1970s. In 1995, Pories et al. 4 reported long term results from 608 severely obese patients who underwent gastric bypass, with a 93% follow-up rate ov...

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“…However, most of the procedures were experimental, and there is lack of evidence and long‐term data. The most interesting procedure was duodenojejunal bypass (DJB), which was inspired by Rubino's animal experiment for the treatment of T2DM 64. However, simple exclusion of the duodenum was found to be less effective than conventional bariatric/metabolic surgery 65.…”

Section: New Procedures With Better Outcomesmentioning

confidence: 99%

Recent advancements in bariatric/metabolic surgery

Lee

Almalki

2017

Annals of Gastroent Surgery

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Obesity and type 2 diabetes mellitus (T2DM) are currently two pan‐endemic health problems worldwide and are associated with considerable increase in morbidity and mortality. Both diseases are closely related and very difficult to control by current medical treatment, including diet, drug therapy and behavioral modification. Bariatric surgery has proven successful in treating not just obesity but also in significantly decreasing overall obesity‐associated morbidities as well as improving quality of life in severely obese patients (body mass index [BMI] >35 kg/m2). A rapid increase in bariatric surgery started in the 2000s when the laparoscopic surgical technique was introduced into this field. Many new procedures had been developed and changed the face of modern bariatric surgery. Recently, bariatric surgery played as gastrointestinal metabolic surgery has been proposed as a new treatment modality for obesity‐related T2DM for patients with BMI >35 kg/m2. Strong evidence has demonstrated that bariatric/metabolic surgery is an effective and durable treatment for obese T2DM patients. Bariatric/metabolic surgery is now becoming an important surgical division. The present article examines and discusses recent advancements in bariatric/metabolic surgery and covers four major fields: (i) the rapid increase in numbers and better safety; (ii) new procedures with better outcomes; (iii) from bariatric to metabolic surgery; and (iv) understanding the mechanisms and personalized treatment.

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Effect of Duodenal–Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes

Cited by 589 publications

References 46 publications

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Recent advancements in bariatric/metabolic surgery

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