Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission

Dutia, Roxanne; Brakoniecki, Katrina; Bunker, Phoebe; Paultre, Furcy; Homel, Peter; Carpentier, André C.; McGinty, James; Laferrère, Blandine

doi:10.2337/db13-1176

Cited by 76 publications

(67 citation statements)

References 36 publications

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“…Although the b-cell response to other stimuli was not tested in the current study, recent evidence consistently shows that residual b-cell function is required for a sustained beneficial effect of RYGB on glucose tolerance even in the context of marked GLP-1 secretion (15). Of note, in study 2 Ex 9-39 was associated with a significant decrease in insulin secretion and total insulin output in both surgical groups, supporting the notion that GLP-1 does potentiate insulin secretion after SG and RYGB (16). Nonetheless, the limited impact of the GLP-1 blockade on both insulin secretion and glucose tolerance after SG suggests that other factors are important.…”

Section: Discussionsupporting

confidence: 64%

GLP-1 and Glucose Tolerance After Sleeve Gastrectomy in Morbidly Obese Subjects With Type 2 Diabetes

et al. 2014

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Although GLP-1 has been suggested as a major factor for the marked improvement of glucose tolerance commonly seen after sleeve gastrectomy (SG), several observations challenge this hypothesis. To better understand the role of GLP-1 in the remission of type 2 diabetes mellitus (T2DM) long term after SG in humans, we conducted two separate cross-sectional studies: 1) the GLP-1 response to a standardized mixed liquid meal (SMLM) was compared in subjects with T2DM antedating SG but with different long-term (>2 years) T2DM outcomes (remission, relapse, or lack of remission) (study 1) and 2) the effect of GLP-1 receptor blockade with exendin (9-39) on glucose tolerance was examined in subjects with T2DM antedating surgery, who had undergone SG and presented with long-term T2DM remission (study 2). In study 1, we observed a comparable GLP-1 response to the SMLM regardless of the post-SG outcome of T2DM. In study 2, the blockade of GLP-1 action resulted in impaired insulin secretion but limited deterioration of glucose tolerance. Thus, our data suggest the enhanced GLP-1 secretion observed long term after SG is neither sufficient nor critical to maintain normal glucose tolerance in subjects with T2DM antedating the surgery.GLP-1 has been suggested as a critical mediator for the marked improvement of glucose tolerance in subjects with type 2 diabetes mellitus (T2DM) commonly seen after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (1). However, this view has been challenged by 1) studies in humans-performed long after RYGB using the GLP-1 receptor antagonist exendin (9-39) (Ex 9-39)-showing that blockade of GLP-1 action results in marked decrease in insulin secretion but limited impact on glucose tolerance (2,3); 2) data showing the GLP-1 response to meal stimuli does not differ between T2DM patients who after RYGB presented with lack of remission, partial remission, or relapse of T2DM (4); and 3) mouse data demonstrating that whole-body GLP-1 receptor deficiency does not influence the glycemic response to SG (5).To gain further insight into the role of GLP-1 in the remission of T2DM long term after SG in humans, We conducted two separate cross-sectional studies: 1) we compared the GLP-1 response to a standardized mixed liquid meal (SMLM) in subjects with T2DM antedating SG but with different long-term (.2 years) T2DM outcomes (remission, relapse, or lack of remission) (study 1) and 2) we examined the effect of GLP-1 receptor blockade with Ex 9-39 on glucose tolerance in subjects with T2DM antedating surgery, who had undergone SG and presented with long-term T2DM remission (study 2). RESEARCH DESIGN AND METHODSParticipants in study 1 (n = 23) were selected out of our series of T2DM patients who had undergone SG at least 2 years before study entry (n = 55), of whom 18 (33%), 31 (56%), and 6 (11%) presented with nonremission, remission, or relapse of T2DM, respectively (6,7). All subjects

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Section: Discussionsupporting

confidence: 64%

GLP-1 and Glucose Tolerance After Sleeve Gastrectomy in Morbidly Obese Subjects With Type 2 Diabetes

et al. 2014

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“…The BCGS and DI measured with the oral glucose test parameters improved rapidly at 1 month and normalized to the levels of the lean and the obese NGT controls at one year. 64 However, BCGS and DI measured after IV glucose administration improved only minimally and remained greatly impaired compared to that of the lean and obese NGT non-operated controls. 64 This experiment highlights the role of the incretins and other gutmediated factors in the amelioration of β-cell response to oral nutrients after RYGBP.…”

Section: Diabetes Relapsementioning

confidence: 99%

“…64 However, BCGS and DI measured after IV glucose administration improved only minimally and remained greatly impaired compared to that of the lean and obese NGT non-operated controls. 64 This experiment highlights the role of the incretins and other gutmediated factors in the amelioration of β-cell response to oral nutrients after RYGBP. It also clearly shows a persistent β-cell defect that cannot be rescued with an IV glucose challenge, 3 years after the surgery, even in persons who are in clinical diabetes remission.…”

Section: Diabetes Relapsementioning

confidence: 99%

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Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.

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“…The article in this issue of Diabetes by Dutia et al (1) shows that in obese diabetic patients returning to normal glucose tolerance (NGT) after gastric bypass b-cell function appears to recover if evaluated through oral glucose tolerance test (OGTT), but not if evaluated through isoglycemic glucose clamp. In fact, the plot indicating Dinsulin/ Dglucose (insulin release [IR]) versus 1/homeostasis model assessment of insulin resistance (HOMA-IR) (insulin sensitivity [IS]) grows during OGTT, but stays flat or moves right, indicating only improvement of IS, during isoglycemic glucose clamp (1).…”

mentioning

confidence: 99%

Comment on Dutia et al. Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission. Diabetes 2014;63:1214−1223

Pontiroli

2014

Diabetes

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Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission

Cited by 76 publications

References 36 publications

GLP-1 and Glucose Tolerance After Sleeve Gastrectomy in Morbidly Obese Subjects With Type 2 Diabetes

GLP-1 and Glucose Tolerance After Sleeve Gastrectomy in Morbidly Obese Subjects With Type 2 Diabetes

Bariatric surgery and obesity: influence on the incretins

Comment on Dutia et al. Limited Recovery of β-Cell Function After Gastric Bypass Despite Clinical Diabetes Remission. Diabetes 2014;63:1214−1223

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