Effects of Gastric Bypass Surgery on Insulin Resistance and Insulin Secretion in Nondiabetic Obese Patients

Abstract

Roux‐en‐Y‐Gastric‐Bypass (RYGB) reduces overall and diabetes‐specific mortality by 40% and over 90%. This study aims to gain insight into the underlying mechanisms of this effect. We evaluated time‐courses of glucose, insulin, C‐peptide, and the incretin glucagon like peptide‐1 (GLP‐1) following an oral glucose load. Insulin‐sensitivity was measured by a hyperinsulinemic‐isoglycemic‐clamp‐test; glucose‐turnover was determined using d‐[6,6‐2H2] glucose. Examinations were performed in six nondiabetic patients with excess weight before (PRE: BMI: 49.3 ± 3.2 kg/m2) and 7 months after RYGB (POST: BMI: 36.7 ± 2.9 kg/m2), in a lean (CON: BMI: 22.6 ± 0.6 kg/m2) and an obese control group (CONob) without history of gastrointestinal surgery (BMI: 34.7 ± 1.2 kg/m2). RYGB reduced fasting plasma concentrations of insulin and C‐peptide (P < 0.01, respectively) whereas fasting glucose concentrations remained unchanged. After RYGB increase of C‐peptide concentration following glucose ingestion was significantly higher compared to all other groups (dynamic‐area under the curve (Dyn‐AUC): 0–90 min: POST: 984 ± 115 ng·min/ml, PRE: 590 ± 67 ng·min/ml, CONob: 440 ± 44 ng·min/ml, CON: 279 ± 22 ng·min/ml, P < 0.01 respectively). Early postprandial increase of glucose concentration was however not affected. GLP‐1 concentrations following glucose ingestion were sixfold higher after RYBG than before (P = 0.01). Insulin‐stimulated glucose uptake tended to increase postoperatively (M‐value: PRE: 1.8 ± 0.5, POST: 3.0 ± 0.3, not significant (n.s.)). Endogenous glucose production (EGP) was unaffected by RYGB. Hepatic insulin resistance index improved after RYGB and was then comparable to both control groups (PRE: 29.2 ± 4.3, POST: 12.6 ± 1.1, P < 0.01). RYGB results in hyper‐secretion of insulin and C‐peptide, whereas improvements of insulin resistance are minor and seem to occur rather in the liver and the adipose tissue than in the skeletal muscle.

Metabolic improvement of morbid obese patients following Roux-en-Y gastric bypass surgery: A prospective study in Mashhad, Iran

“…Kashyap et al in a prospective trial on 60 subjects with uncontrolled T2DM and moderate obesity reported improvement of pancreatic β cell function after RYGB surgery but not after sleeve gastrostomy [32]. Additionally, plasma concentration levels of insulin had been reported to reduce after RYGB, but the post-prandial response had been exaggerated [33]. In aggregate, the authors want to emphasize that combining surgery with medical therapy are suggested for severely and morbidly obese patients who suffer from T2DM.…”

Impaired glucose regulation is associated with poorer performance on the Stroop Task

“…One recent study demonstrated improved memory performance following weight loss after bariatric surgery [49]. Although glucose concentrations were not reported, it is likely that they decreased significantly following bariatric surgery [50]. Several studies have found that reducing glucose levels through treatment with medication resulted in improvements in cognitive performance [51] [52], including Stroop-word naming [53].…”

Gastrointestinal changes after bariatric surgery

“…These improvements are potentially related to the increased GLP-1 levels also observed after surgery, however further studies are required to understand this potential insulin-sensitizing effect on the liver. In humans, nondiabetic obese patients after RYGB showed improved hepatic insulin index, high levels of insulin and C-peptide and unchanged endogenous glucose production, compared to lean and obese control groups [77]. Furthermore, type 2 diabetes subjects one-month post-RYGB had improved HGP and hepatic insulin sensitivity index without an associated improvement in peripheral insulin sensitivity, demonstrating that RYGB can improve hepatic metabolism [78].…”