Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes

Laferrère, Blandine; Heshka, Stanley; Wang, Krystle; Khan, Yasmin; McGinty, James; Teixeira, Júlio; Hart, Allison; Oliván, Blanca

doi:10.2337/dc06-1549

Cited by 469 publications

(417 citation statements)

References 63 publications

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“…In contrast, the effect of RYGB on GLP1 is quite different from that of BPD. After RYGB, an increase in the GLP1 level after OGTT or a meal was observed in people with NGT [14] and in diabetic patients [12,13], and was associated with increased circulating levels of insulin.…”

Section: Discussionmentioning

confidence: 99%

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Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

et al. 2009

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Aims/hypothesis We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. Methods Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Withinday variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp.Results Basal GLP1 relative amplitude (amplitude/ mesor× 100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775± 94 to 846± 161 pmol l −1 min in NGT, whereas GIP AUC decreased significantly from 1,373± 565 to 513± 186 pmol l −1 min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p =0.010) and GLP1 AUCs (p =0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD× diabetes, p =0.003). Insulin sensitivity was markedly improved (p< 0.01) in NGT (from 9.14± 3.63 to 36.04 ±8.55 µmol [kg fat-free mass] −1 min −1 ) and diabetic patients (from 9.49± 3.56 to 38.57± 4.62 µmol [kg fat-free mass] −1 min −1 ). Conclusions/interpretation An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.Keywords Bariatric surgery . Circadian rhythm . GIP . GLP1 . Morbid obesity Abbreviations BPDBiliopancreatic diversion FFM Fat-free mass GIP Glucose-dependent insulinotropic polypeptide GLP1 Glucagon-like peptide 1 NGT Normal glucose tolerance RYGB Roux-en-Y gastric bypass Diabetologia (2009) 52:873-881

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Section: Discussionmentioning

confidence: 99%

“…Relatively few data are available concerning the effect of bariatric surgery on incretin secretion [10][11][12][13][14][15] and, at least to our knowledge, no data exist regarding the response of incretin to multiple meals.…”

Section: Introductionmentioning

confidence: 99%

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

et al. 2009

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“…Nevertheless, recent studies clearly show that meal-stimulated secretion of GLP-1 and other L-cell peptides such as peptide YY is, indeed, substantially and durably increased after RYGB, whereas this does not occur after AGB. 27,28,40,41 Consistent with elevated postprandial GLP-1 secretion, post-RYGB patients display an increased incretin effect. 25,40 As GLP-1 not only enhances insulin secretion but can also increase proliferation and decrease apoptosis of b cells, 39 it is a candidate mediator of the increase in b-cell mass that is claimed by some investigators to accompany post-RYGB hyperinsulinemic hypoglycemia.…”

Section: The Lower Intestinal Hypothesismentioning

confidence: 99%

“…27,28,40,41 Consistent with elevated postprandial GLP-1 secretion, post-RYGB patients display an increased incretin effect. 25,40 As GLP-1 not only enhances insulin secretion but can also increase proliferation and decrease apoptosis of b cells, 39 it is a candidate mediator of the increase in b-cell mass that is claimed by some investigators to accompany post-RYGB hyperinsulinemic hypoglycemia. 30,31 Further support for the lower intestinal hypothesis comes from experiments involving ileal interposition.…”

Section: The Lower Intestinal Hypothesismentioning

confidence: 99%

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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“…Of note, the improvement in glycemic control observed after RYGB occurs within a few days after surgery, and it seems to occur before any significant weight loss or increase in insulin sensitivity (5,9). Early after RYGB surgery, an enhanced insulin secretion rate and enhanced circulating GLP-1 levels have been documented (10,11). However, it takes months before peripheral insulin sensitivity is detected (9,12), which parallels enhanced muscle expression of GLUT4, enhanced mitochondrial respiration, and enhanced phosphorylation of Akt and TBC1D4 (13)(14)(15).…”

mentioning

confidence: 99%

The Muscle Race After Bariatric Surgery: Ribosomal Proteins Come First

Hernández‐Álvarez

Zorzano

2016

Diabetes

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Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes

Cited by 469 publications

References 63 publications

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

The Muscle Race After Bariatric Surgery: Ribosomal Proteins Come First

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