An Integrated Model for Glucose and Insulin Regulation in Bariatric Surgery Patients following Intravenous Glucose Tolerance Test
Stefanie K. Drescher (1), Raja Venkatasubramanian (1), Paul Coen (2), Bret Goodpaster (2), Mirjam N. Trame (1)
(1) Center for Pharmacometrics and Systems Pharmacology, Dept. of Pharmaceutics, University of Florida, Orlando, FL, USA, (2) Translational Research Institute for Metabolism & Diabetes, Orlando, FL, USA
Objectives: Gastric Bypass Surgery (GBS) is a common treatment option for severe obesity. GBS induces weight loss but also improves glucose control by reducing muscle and liver insulin resistance and improving β-cell function [1,2]. Exercise is also effective at improving glucose control in GBS patients. So far these changes have not been quantitatively described by an integrated glucose-insulin model. Our objective was to develop an intravenous glucose tolerance test (IVGTT) model to predict improvements in insulin and glucose regulation in patients following GBS alone and with a 6-month exercise intervention.
Methods: Data from GBS patients with (n=60; treatment group) and without (n=59, control group) regular exercise after GBS were available from a previously conducted RTC [3]. IVGTT was conducted for the first time directly after bariatric surgery prior to any exercise intervention and repeated after a six month intervention period with and without exercise. The randomized controlled physical activity intervention was defined as minimum three and maximum of five exercise sessions weekly. A previously developed IVGTT model by Silber et al. [4] was used as a starting point. Disease progression was included and tested on varies parameters to evaluate and compare differences in glucose and insulin regulation between the control and the exercise group post GBS.
Results: The developed quantitative model was able to adequately describe the insulin-glucose-homeostasis in all subjects after IVGTT. Subjects in both groups, control and exercise, were found to overall have improved insulin dependent glucose clearance on their second visit. Additionally, subjects in the exercise group were found to have better insulin dependent glucose clearance and improved feedback to glucose production when compared to subjects in the control group. This was seen in a faster return of glucose levels after administration of intravenous glucose.
Conclusions: Based on clinical observations, a quantitative model was built to describe the interaction between glucose and insulin simultaneously in GBS patients after IVGTT. The results indicate that GBS has a positive influence on glucose-insulin-regulation and that additional exercise post GBS will result in further improvements. For the first time an IVGTT model was developed in post GBS patients helping to improve our understanding of the insulin-glucose-homeostasis in this patient population.
References:
[1] Després J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006; 444 (7121): 881–7
[2] Pok E-H, Lee W-J. Gastrointestinal metabolic surgery for the treatment of type 2 diabetes mellitus. World J Gastroenterol WJG. 2014; 20(39): 14315–28
[3] Coen PM, Tanner CJ, et al. Clinical trial demonstrates exercise following bariatric surgery improves insulin sensitivity. J Clin Invest. 2015; 125(1):248-257
[4] Silber H-E, Jauslin P-M, et al. An Integrated Model for Glucose and Insulin Regulation in Healthy Volunteers and Type 2 Diabetic Patients Following Intravenous Glucose Provocations. Journal of Clinical Pharmacology, 2007; 47: 1159-1171
