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

Columbia University, New York, New York, United States
Diabetes care (Impact Factor: 8.42). 07/2007; 30(7):1709-16. DOI: 10.2337/dc06-1549
Source: PubMed


Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP.
Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test.
Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 +/- 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 +/- 7.9 pmol x l(-1) x min(-1) (P < 0.0001) and 131 +/- 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 +/- 28.7 to 42.5 +/- 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 +/- 23.5%, P = 0.284).
These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.

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Available from: James Mcginty, Oct 28, 2014
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    • "h after GB , a more than fourfold increase in the incretin effect was observed , alongside with amelioration of fasting blood glucose and a significantly augmented glucose - stimulated GLP - 1 secretion . In comparison to the non - diabetic obese control group , the enhanced incretin effect in operated diabetic patients reached comparable values ( Laferrère et al . , 2007 ) A postoperative decrease in fasting plasma GIP levels in obese diabetic patients was observed after GB and associated with normalization of blood glucose and fasting insulin , indicating a role for incretin metabolism in the amelioration of glucose homeostasis after duodenal exclusion ( Rubino et al . , 2004 ) . In non - diabetic obes"

    Full-text · Thesis · Feb 2015
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    • "After GB, and to lesser extent after SG, meal ingestion results in earlier and higher peaks of glucose as well as rapid declines to a lower glucose nadir. In parallel there is a similar pattern of insulin and GLP-1 secretion with earlier and larger peaks compared to people without surgery [20, 25, 27–30] (Fig. 1). This pattern is due in part to more rapid transit of nutrients into the small intestine from the restricted gastric compartments that inherent to these surgeries. "
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    ABSTRACT: To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment of obesity, induce diabetes remission independent of weight loss while glucose improvement after adjustable gastric banding (AGB) is proportional to the amount of weight loss. The immediate, weight-loss independent glycemic effect of gastric bypass has been attributed to postprandial hyperinsulinemia and an enhanced incretin effect. The rapid passage of nutrients into the intestine likely accounts for significantly enhanced glucagon like-peptide 1 (GLP-1) secretion, and postprandial hyperinsulinemia after GB is typically attributed to the combined effects of elevated glucose and GLP-1. For this review we focus on the beneficial effects of the three most commonly performed bariatric procedures, RYGB, SG, and AGB, on glucose metabolism and diabetes remission. Central to this discussion will be the extent to which the effects of surgery are mediated by GLP-1. Better understanding of these mechanisms could provide insight to development of novel therapeutic strategies for treatment of diabetes as well as refinement of surgical techniques.
    Preview · Article · Jun 2014 · Reviews in Endocrine and Metabolic Disorders
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    • "As a first instance, there is a greater insulin sensitivity due to a better β-cell function including the first phase of insulin secretion [120]. Also, there is restoration of a near-normal, postprandial insulin response soon after RYGBP [121], which is associated with a rise in GLP-1 levels [122]. Even more, ghrelin levels fall after RYGBP [109], resulting in appetite reduction. "
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    ABSTRACT: In the physiological state a multitude of gut hormones are released into the circulation at the same time depending on the quality and quantity of the diet. These hormones interact with receptors at various points in the “gut-brain axis” to affect short-term and intermediate-term feelings of hunger and satiety. The combined effects of macronutrients on the predominant gut hormone secretion are still poorly understood. Besides, adipokines form an important part of an “adipoinsular axis” dysregulation which may contribute to β -cell failure and hence to type 2 diabetes mellitus (T2DM). Even more, gestational diabetes mellitus (GDM) and T2DM seem to share a genetic basis. In susceptible individuals, chronic exaggerated stimulation of the proximal gut with fat and carbohydrates may induce overproduction of an unknown factor that causes impairment of incretin production and/or action, leading to insufficient or untimely production of insulin, so that glucose intolerance develops. The bypass of the duodenum and jejunum might avoid a putative hormone overproduction in the proximal foregut in diabetic patients that might counteract the action of insulin, while the early presentation of undigested or incompletely digested food to the ileum may anticipate the production of hormones such as GLP1, further improving insulin action.
    Full-text · Article · Dec 2013 · International Journal of Endocrinology
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