Delivery of Nutrient Directly to the Upper Intestine Enhances the Release of Endogenous Incretins in Type 1 Diabetes

Presentation Number: MON 582
Date of Presentation: April 3rd, 2017

Elizabeth O Beale*1, WeiAn Lee1, Marshall Ge1 and Viorica Ionut2
1University of Southern California, LA, CA, 2Cedars Sinai Medical Center, LA, CA

Abstract

Intestinal K and L cells release the glucoregulatory incretin hormones GLP-1 and GIP in response to nutrient ingestion. As these hormones have insulin-independent actions, enhancing their release in individuals with type 1 diabetes might improve glucose control. Delivery of a mixed meal (MM) by feeding tube (FT) to the upper intestine (UI) in normal individuals and those with type 2 diabetes enhances the release of incretins; however, little is known about endogenous incretin regulation in type 1 diabetes. The aim of this pilot study was to determine if, in adults with type 1 diabetes, incretin levels and glucose tolerance were increased by delivery of a MM by FT directly to the UI compared with oral and intragastric routes. Seven fasting adults with type 1 diabetes underwent three 11-sample 3-hour MM tolerance tests: once with the MM taken orally (control 1), once via FT to the stomach (control 2), and once via FT to the UI (intervention). Post-pyloric FTs were placed in the distal duodenum in alert subjects under electromagnetic guidance. (EAS™; CORPAK MedSystems, Il.) A weight-based dose of 0.06kcal/kg/min MM (1kcal/ml) was given steadily over 30 mins for all routes. GLP-1 levels for the UI route were significantly higher than those for the oral route at 15 mins (p=.012), 30 mins (p<.001), and 45 mins (p=.001). GLP-1 levels for the UI route were significantly higher than for the gastric route only at 45 mins (p=.035). The iAUC GLP-1 was greatest for the UI route, intermediate for the gastric route, and least for the oral route, with difference between UI and oral routes reaching statistical significance (p=.01). For GIP, the UI route had significantly higher levels compared to those with the oral and gastric routes at 15 mins (p=.028 and p=.001 respectively) and 30 mins (p=.017 and p=.007 respectively), but no significant differences were found among the three routes for the subsequent time points. The iAUC for GIP was not significantly different among the three routes. C-peptide levels at each time point and iAUC were not statistically different among the three routes. Glucose levels at each time point including peak, and iAUC were not significantly different among the three routes. However, comparison of the drop in glucose levels from the 45 minute peak to the 180 minute end-of-study revealed that the UI route had a significantly larger drop in glucose during this period than with the oral route (p=.02). Measures of satiety and adverse effects did not differ by route. Adverse effects were minimal for all routes of delivery. We speculate that intragastric meal administration accelerated nutrient delivery to the UI by directing it through the pylorus, thereby leading to higher levels of incretins than seen with the oral route. Activation of endogenous incretins with targeted nutrient stimulation warrants further evaluation as a non-pharmacological therapeutic strategy for insulin-independent glucose control.

 

Nothing to Disclose: EOB, WL, MG, VI