Insulin Clearance After Oral and Intravenous Glucose Following Gastric Bypass and Gastric Banding Weight Loss

Abstract

Hepatic insulin clearance is a significant regulator of glucose homestasis. We hypothesized that the improvement in insulin clearance rates (ICRs) under fasting conditions and in response to oral and intravenous (IV) glucose would improve similarly after Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) as a function of weight loss; the difference in ICR after oral and IV glucose stimulation will be enhanced after RYGB compared with AGB, an effect mediated by glucagon-like peptide 1 (GLP-1). RESEARCH DESIGN AND METHODS In study 1, the ICR was calculated under fasting condition (F-ICR), after oral glucose (O-ICR), and after an isoglycemic IV glucose clamp (IV-ICR) in individuals from an established cohort with type 2 diabetes mellitus (T2DM) before, after 10% matched weight loss, and 1 year after either RYGB (n = 22) or AGB (n = 12). In study 2, O-ICR was studied in a separate cohort of individuals with T2DM (n = 22), before and 3 months after RYGB, with and without exendin(9-39) infusion. RESULTS In study 1, age, BMI, T2DM duration and control, and ICR did not differ between RYGB and AGB preintervention. Weight loss at 1 year was two times greater after RYGB than after AGB (31.6 6 5.9% vs. 16.6 6 9.8%; P < 0.05). RYGB and AGB both significantly increased F-ICR, O-ICR, and IV-ICR at 1 year. ICR was inversely associated with insulinemia. The difference between IV-ICR and O-ICR was significantly greater after RYGB versus AGB. GLP-1 antagonism with exendin(9-39) led to an increase in O-ICR in subjects post-RYGB. CONCLUSIONS Weight loss increased ICR, an effect more pronounced after RYGB compared with AGB. Our data support a potential role for endogenous GLP-1 in the control of postprandial ICR after RYGB. Hyperinsulinemia is a risk factor for cardiovascular disease (1). Circulating concentrations of insulin are dependent on b-cell insulin secretion capacity and insulin clearance from the blood (2). About 70% of secreted insulin is cleared by the liver prior to entering the systemic circulation (3). Hepatic insulin clearance rate (ICR) is decreased in many aspects of the metabolic syndrome, such as obesity (4), hypertension, hypertriglyceridemia, and glucose intolerance (5).

Effects of Obesity Surgery on Blood Coagulation and Fibrinolysis: A Literature Review

“…Further, surgery favorably affects lipids, glucose, insulin, HBA1c, and insulin resistance. 88 It is unknown, whether the hemostatic changes are mediated by weight loss alone or by the accompanying metabolic improvements. In one study, Lupoli et al compared RYGB and SG with respect to 13 hemostatic biomarkers 2 months after surgery, and the surgical techniques affected weight loss equally, but eight of the measured biomarkers were significantly lower after RYGB than after SG.…”

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

“…Since there is currently no consensus on the best use of hypoglycemic compounds after bariatric procedure [104] , the evaluation of beta cell functionality may help in the post-surgical follow up of patients with T2D in order to reduce the hypoglycemic or hyperglycemic events during the post-surgical period if diabetes therapy is not adequately adapted to the evolution of beta cell function. However, variable clearance of insulin depending on bariatric procedure, time after surgery and gut peptides complicates the evaluation of beta cell function [15] , [16] , [17] . Thus, in the era of personalized medicine, measurement of the circulating levels of the four miRNAs discovered here, and conserved across species, could provide an important tool to obtain information on beta cell function.…”

“…For exendin [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] amide infusion experiments, the intraperitoneal cavity of EGA-ob mice was continuously infused for 28 days with exendin [9–39] amide (Sigma Aldrich®, ref E7269) at the rate of 2 pmol. kg −1 .min −1 (6,74 −06 mg. kg −1 .min −1 ) or NaCl (0.9%) with an osmotic minipump (Alzet Model 2004; Alza, Palo Alto, CA).…”

“…In some patients, it occurs independently of weight loss soon after bariatric surgery [5] and in others later, where it is more dependent on changes in weight [14] . Although it is critical to monitor the impact of diabetes therapy [15] , [16] , [17] , post-surgical evaluation of endocrine pancreas function by measurement of classical parameters such as insulin or C-peptide can be difficult. The assessment of circulating biomarkers of beta cell function evolution may therefore be useful during post-surgical follow up and may help to adapt therapy and limit the occurrence of hypoglycemic or hyperglycemic events.…”

Proinsulin associates with poor β‐cell function, glucose‐dependent insulinotropic peptide, and insulin resistance in persistent type 2 diabetes after Roux‐en‐Y gastric bypass in humans

“…Prior to surgery, a longer duration of T2D, having poorly controlled T2D, being treated with insulin and/or multiple oral agents, and having poor β-cell function 3,4 are the main determinants of non-remission and/or relapse after RYGB. Important determinants after surgery include the weight loss amount, the degree of improvement in insulin sensitivity 5 and clearance, 6 the enhanced postprandial release of the incretins glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), and restoration of the incretin effect on insulin secretion, all of which contribute to better glucose control. 7 Although weigh regain plays little role in relapse, 2 time since surgery is ultimately a key variable because diabetes remission rate decreases over time.…”