Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

Background We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking. Methods Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching. Results HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05). Conclusions Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW. Trial registration Clinical trial registry number; UMIN000016390 and jRCTs031180320. Approval date of Registry and the Registration: December 12, 2014.

Gastrointestinal motility and Intestinal structure following oral exposure to acrylamide in Wistar rats

Introduction: Acrylamide, a byproduct of the cooking process, has been reported to be a toxicant with likely carcinogenic properties. Its impairment of gastric function has been previously reported. In this study its effects on gastrointestinal motility and intestinal structure was investigated in male Wistar rats.Methods: Forty-five rats (120-180g) were divided into 3 equal groups (n=15) and treated p.o with either 0.2ml distilled-water, or acrylamide (7.5mg/kg and 15mg/kg respectively) for 28days. Thereafter, gastric emptying and intestinal motility was assessed. Intestinal structure (duodenum, jejunum and ileum), mucosal and intestinal cell counts were evaluated using histological techniques.Results: Gastric emptying and intestinal transit time increased (p<0.05) in the experimental (acrylamidetreated; 7.5mg/kg and 15mg/kg) groups compared to control. Mucosal cell counts (duodenum, jejunum and ileum) and ileum intestinal cell counts (p<0.05) were reduced in the experimental groups compared to control. Compared to control, duodenal samples of the experimental groups showed severe coagulative necrosis and sloughing off of the villi, luminal filling with necrotic debris, disruption and necrosis of the crypts of Lieberkühn, moderate polymorphonuclear cell infiltration and vascular congestion. These pathologies albeit with less severity were also observed in the jejunum and ileum of acrylamide treated groups.Conclusion: Increased oral exposure to acrylamide impairs gastric emptying, intestinal motility, mucus secretion and compromises digestive and absorptive functions of the small intestines, especially the duodenum. These observations may be ascribed to acrylamide-induced impaired neuronal signaling, autonomic neuropathy, oxidative stress, inflammation and cell necrosis. Keywords: Acrylamide, gastrointestinal tract, gastric emptying, intestinal motility, small intestines

Rising Temperature Effects on Growth and Gastric Emptying Time of Freshwater African Catfish (Clarias Gariepinus) Fingerlings

The present study was carried out to analyse the effect of water temperature on two components: (1) growth performance, and (2) gastric emptying time (GET) of African catfish Clarias gariepinus fingerlings. After 70 days, it was observed that experimental temperatures had no significant effects on the growth performance parameters, except for food conversion ratio (FCR) and food conversion efficiency (FCE). GET observation through X-radiography denoted that the shortest GET (10 h) was observed in fish reared at 32 °C and the longest GET (16 h) was observed in fish reared at 26 °C. The rapid digestion rate coincides with the FCR and FCE obtained in this study. Considering the limited scope of our study, more extensive studies on the impact of water temperature on other fish physiological parameters should be pursued. A better understanding of this research topic would be beneficial for the growth of African catfish fingerling aquaculture.