Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes

Kashyap, Sangeeta R.; Bhatt, Deepak L.; Wolski, Kathy; Watanabe, Richard M.; Abdul‐Ghani, Muhammad; Abood, Beth; Pothier, Claire E.; Brethauer, Stacy A.; Nissen, Steven E.; Gupta, Manjula K.; Kirwan, John P.; Schauer, Philip R.

doi:10.2337/dc12-1596

Cited by 261 publications

(199 citation statements)

References 32 publications

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“…Two years after surgery, insulin sensitivity was significantly increased by 2.7-fold from baseline and b-cell function (disposition index) was increased 5.8-fold (22). The reduction in abdominal (truncal) fat was inversely correlated with the b-cell function.…”

mentioning

confidence: 71%

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

Schirra

Göke

2014

Diabetes

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The worldwide increase in obesity is associated with a higher prevalence of type 2 diabetes (T2D), and severe obesity occurs with the greatest risk (1). Bariatric surgery is currently the most effective treatment not only for weight loss but also for prevention or treatment of T2D in such patients (2). It leads to remission or improvement of T2D in the majority of morbidly obese (3,4). Roux-en-Y gastric bypass (RYGB) is one of the most frequently performed procedures. With RYGB, the stomach is reduced to a small proximal pouch (30-50 mL) and anastomosed to the jejunum, thereby bypassing the majority of the stomach and duodenum. After RYGB, T2D improves rapidly often before significant weight loss occurs. The mechanisms behind this phenomenon are not clearly resolved. Caloric restriction contributes. Extreme caloric restriction to the limit just tolerated in patients after surgery improved insulin resistance in obese subjects similarly as found in after the first week after RYGB (5). Of interest, the malabsorptive component of the RYGB procedure approximately accounts only for up to 11% of the total reduction in combustible energy absorption (6). Changes of adipokine-induced inflammation and insulin resistance (7) and reduction of branched-chain amino acids correlating with insulin resistance (8) have been proposed as further mechanisms operating after bariatric surgery complementing the sole weight loss.A popular hypothesis points to an antidiabetic effect after RYGB of postprandially exaggeratedly released gut peptides, such as glucagon-like peptide 1 (GLP-1), already starting early after surgery. The release of GLP-1 depends on gastric emptying (GE) velocity (9). It lowers postprandial glycemia by stimulation of insulin, inhibition of glucagon secretion, and delay of GE. For example, Laferrère et al. (10) reported a sixfold increase in GLP-1 plasma levels and a fivefold increase of the incretin effect in obese patients with T2D 1 month after RYGB. In this issue, Shah et al. (11) addressed the contribution of endogenous GLP-1 to the meal-induced glucose metabolism, islet secretion, and GE after RYGB in 12 nondiabetic obese patients 5 6 0.9 years after RYGB and 8 weightmatched control subjects twice using the GLP-1 receptor (GLP-1R) antagonist exendin(9-39). After ingestion of a 220 kcal mixed-meal, glucose metabolism was measured using the isotope dilution method. Indices of insulin action and b-cell glucose responsitivity and the resulting glucose disposition indices were calculated using the oral minimal model. GE was measured by scintigraphy. As expected, GE (gastric pouch in the post-RYGB subjects) was greatly accelerated, leading to a several-fold increase in postprandial GLP-1, insulin, and C-peptide responses after RYGB. The GLP-1R antagonist increased the postprandial glucose excursions in both groups. Exendin(9-39) decreased insulin and C-peptide concentrations in subjects post-RYGB by about 30% with no effect in control subjects. The calculated b-cell response to glucose was significantly reduced in b...

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confidence: 71%

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

Schirra

Göke

2014

Diabetes

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“…The reason for this remains a controversy, as studies have shown that the beneficial effects of RYGB on T2D are weight loss independent (e.g., [3]), while others suggest that they result from reduced food intake (4). Clinical studies have shown that RYGB has greater effect on remission of T2D than, for example, vertical sleeve gastrectomy, despite similar weight loss (5). This is in support of weight-independent factors underlying the resolution of T2D upon RYGB.…”

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confidence: 97%

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

et al. 2014

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The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on b-cell function and b-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in b-cell mass, islet number, and number of extraislet b-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved b-cell function and b-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.Roux-en-Y gastric bypass surgery (RYGB) leads to remission of type 2 diabetes (T2D) in most patients within days after surgery (1). Importantly, this occurs long before any substantial weight loss has occurred (2). The reason for this remains a controversy, as studies have shown that the beneficial effects of RYGB on T2D are weight loss independent (e.g., [3]), while others suggest that they result from reduced food intake (4). Clinical studies have shown that RYGB has greater effect on remission of T2D than, for example, vertical sleeve gastrectomy, despite similar weight loss (5). This is in support of weight-independent factors underlying the resolution of T2D upon RYGB. One factor, accounting for the beneficial metabolic effects of RYGB, may be changes in circulating levels of gut hormones and their effects on the islets. In particular, increased levels of the incretin hormone glucagon-like peptide 1 (GLP-1) have been implicated as a factor contributing to remission of T2D (2,6). The effect of RYGB on glucose-dependent insulinotropic peptide (GIP) is less clear (6,7). Other factors, including gut microbiota (8), intestinal glucose sensing (9), and bile acids (10), may also contribute. Nevertheless, it is of great clinical importance to resolve this issue, as it will have a strong impact on how treatment for a large group of patients is devised. In fact, if a specific mechanism were to be identified, it could be used as the basis for a new treatment modality.One problem in the dissection of effects of RYGB on glucose metabolism is that studies on b-cell mass in humans are lacking, and it is extremely difficult to generalize from data in rodents (11) because of huge differences in pancreatic anatomy and physiology between the species. To circumvent these problems, we devel...

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“…In a prespecified substudy analysis of beta-cell function, insulin sensitivity, and body composition in a subgroup of patients, we found that at 2 years, gastric bypass was superior to sleeve gastrectomy with respect to insulin secretion, insulin sensitivity, and relative reduction in truncal fat as compared with subcutaneous fat. 20 Most clinical guidelines and insurance coverage for bariatric surgery limit access to the surgery to patients with a BMI of 35 or more, presumably because of insufficient studies evaluating outcomes in patients with a BMI of less than 35. In our study, 49 of 137 patients (36%) had a BMI of 27 to 34, and these patients had an improvement in glycemic control and durability that was similar to that in patients with a BMI of 35 or more.…”

Section: Discussionmentioning

confidence: 99%

Bariatric surgery versus intensive medical therapy for diabetes -5- year outcomes

Genser¹,

Barrat

2017

Obes

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Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes

Cited by 261 publications

References 32 publications

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

GLP-1—A Candidate Humoral Mediator for Glucose Control After Roux-en-Y Gastric Bypass

Gastric Bypass Improves β-Cell Function and Increases β-Cell Mass in a Porcine Model

Bariatric surgery versus intensive medical therapy for diabetes -5- year outcomes

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